2021/11/30 更新

写真a

ワタナベ マサミ
渡部 昌実
WATANABE Masami
所属
岡山大学病院 教授
職名
教授
外部リンク

学位

  • 医学博士 ( 岡山大学 )

研究キーワード

  • 悪性腫瘍

  • 細胞治療

  • 遺伝子治療

  • 再生医療

  • 泌尿器科

研究分野

  • ライフサイエンス / 泌尿器科学

経歴

  • 岡山大学   Okayama University Hospital

    2016年2月 - 現在

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  • 岡山大学   Okayama University Hospital

    2010年4月 - 2016年1月

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  • 岡山大学   Okayama University Hospital

    2009年 - 2010年3月

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  • 岡山大学医歯薬学総合研究科 特別契約職員助手・助教

    2006年 - 2009年

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  • ベイラー医科大学 博士研究員

    2004年 - 2006年

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  • 岡山中央病院 医師

    2001年 - 2003年

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  • 高知県立中央病院 医師

    2000年 - 2001年

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  • 岡山赤十字病院 レジデント

    1996年 - 2000年

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▼全件表示

 

論文

  • In vivo evaluation of GG2-GG1/A2 element activity in the insulin promoter region using the CRISPR-Cas9 system. 国際誌

    Hirofumi Noguchi, Chika Miyagi-Shiohira, Takao Kinjo, Issei Saitoh, Masami Watanabe

    Scientific reports   11 ( 1 )   20290 - 20290   2021年10月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-021-99808-6

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  • Efficacy of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis: A phase II clinical trial. 国際誌

    Takuya Sadahira, Koichiro Wada, Motoo Araki, Ritsuko Mitsuhata, Masumi Yamamoto, Yuki Maruyama, Takehiro Iwata, Masami Watanabe, Toyohiko Watanabe, Reiko Kariyama, Yasutomo Nasu, Ayano Ishii

    International journal of urology : official journal of the Japanese Urological Association   28 ( 10 )   1026 - 1031   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/iju.14636

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  • Impact of Sarcopenia on Erectile Function after Nerve-Sparing Robot-Assisted Radical Prostatectomy. 国際誌

    Yosuke Mitsui, Takuya Sadahira, Yuki Maruyama, Ryota Sato, Acosta Gonzalez, Herik Rodrigo, Koichiro Wada, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    The world journal of men's health   39 ( 4 )   673 - 682   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.5534/wjmh.200036

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  • Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms. 国際誌

    Shogo Watari, Motoo Araki, Jun Matsumoto, Kasumi Yoshinaga, Takanori Sekito, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Koichiro Wada, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Noritaka Ariyoshi, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Drug metabolism and pharmacokinetics   40   100407 - 100407   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.dmpk.2021.100407

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  • Presence of decoy cells for 6 months on urine cytology efficiently predicts BK virus nephropathy in renal transplant recipients. 国際誌

    Takanori Sekito, Motoo Araki, Kasumi Yoshinaga, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Tanabe, Hidemi Takeuchi, Hiroshi Morinaga, Masashi Kitagawa, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Hiroyuki Yanai, Yasutomo Nasu

    International journal of urology : official journal of the Japanese Urological Association   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/iju.14679

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  • The Cell Cycle Checkpoint Gene, RAD17 rs1045051, Is Associated with Prostate Cancer Risk. 査読 国際共著

    Jingkai Sun, Wenfeng Lin, Qixu Wang, Akiko Sakai, Ruizhi Xue, Masami Watanabe, Chunxiao Liu, Takuya Sadahira, Yasutomo Nasu, Abai Xu, Peng Huang

    Acta medica Okayama   75 ( 4 )   415 - 421   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/62379

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  • Successful deceased donor kidney transplantation to a recipient with a history of COVID-19 treatment. 国際誌

    Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Kou Hasegawa, Takanori Sekito, Shuji Miyake, Shogo Watari, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Katsuyuki Tanabe, Hidemi Takeuchi, Yuri Nakashima, Masaru Kinomura, Herik Acosta, Yosuke Mitsui, Risa Kubota, Hirochika Nakajima, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Fumio Otsuka, Jun Wada, Yasutomo Nasu

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 7 )   1097 - 1101   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jiac.2021.03.018

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  • Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer. 国際誌

    Nobuyuki Yanagisawa, Takefumi Satoh, Ken-Ichi Tabata, Hideyasu Tsumura, Yasutomo Nasu, Masami Watanabe, Timothy C Thompson, Isao Okayasu, Yoshiki Murakumo, Shiro Baba, Masatsugu Iwamura

    Asian journal of urology   8 ( 3 )   280 - 288   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ajur.2020.06.004

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  • Feasible kidney donation with living marginal donors, including diabetes mellitus. 国際誌

    Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Takanori Sekito, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Katsuyuki Tanabe, Hidemi Takeuchi, Masashi Kitagawa, Shinji Kitamura, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Immunity, inflammation and disease   9 ( 3 )   1061 - 1068   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/iid3.470

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  • Comparison of intracorporeal versus extracorporeal urinary diversion after robot-assisted radical cystectomy at a medium-sized facility.

    Takehiro Iwata, Yasuyuki Kobayashi, Yuki Maruyama, Tatsushi Kawada, Takuya Sadahira, Yuko Oiwa, Satoshi Katayama, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Koichiro Wada, Kohei Edamura, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    International journal of clinical oncology   26 ( 9 )   1714 - 1721   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10147-021-01957-1

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  • The number of glutamines in the N-terminal of the canine androgen receptor affects signalling intensities. 国際誌

    Kazuhiko Ochiai, Samak Sutijarit, Mitsuki Uemura, Masami Morimatsu, Masaki Michishita, Eri Onozawa, Marika Maeda, Takanori Sasaki, Masami Watanabe, Yoshikazu Tanaka, Toshinori Omi

    Veterinary and comparative oncology   19 ( 2 )   399 - 403   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/vco.12663

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  • A Case of Metastatic Fumarate Hydratase-Deficient-like Renal Cell Carcinoma Successfully Managed by Ipilimumab plus Nivolumab.

    Takanori Sekito, Atsushi Takamoto, Yasuyuki Kobayashi, Masao Mitsui, Shogo Watari, Risa Kubota, Takuya Sadahira, Takehiro Iwata, Shingo Nishimura, Kohei Edamura, Tomoko Sako, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Rei Shibata, Daisuke Ennishi, Yasutomo Nasu

    Acta medica Okayama   75 ( 3 )   397 - 402   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/62237

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  • ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study. 国際誌

    Shogo Watari, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Transplantation proceedings   53 ( 5 )   1494 - 1500   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.transproceed.2021.03.043

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  • Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging. 国際誌

    Yuki Maruyama, Motoo Araki, Kengo Kidokoro, Yuji Sogawa, Kasumi Yoshinaga, Yosuke Mitsui, Takuya Sadahira, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Naoki Kashihara, Yasutomo Nasu

    Transplantation   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/TP.0000000000003803

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  • Pancreas preservation with amphotericin B deteriorates islet yield for porcine islet isolation. 国際誌

    Sayaka Sawada, Chika Miyagi-Shiohira, Kazuho Kuwae, Yoshihito Tamaki, Kai Nishime, Mayuko Sakai-Yonaha, Tasuku Yonaha, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    Xenotransplantation   28 ( 4 )   e12690   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/xen.12690

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  • Impact of paclitaxel, cisplatin, and gemcitabine as first-line chemotherapy in cisplatin-fit and -unfit patients with advanced/metastatic urothelial carcinoma. 国際誌

    Satoshi Katayama, Yasuyuki Kobayashi, Atsushi Takamoto, Kohei Edamura, Takuya Sadahira, Takehiro Iwata, Shingo Nishimura, Tomoko Sako, Koichiro Wada, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Urologic oncology   39 ( 10 )   731.e25-731.e32   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.urolonc.2021.02.029

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  • Photodynamic diagnostic ureteroscopy using the VISERA ELITE video system for diagnosis of upper-urinary tract urothelial carcinoma: a prospective cohort pilot study. 国際誌

    Koichiro Wada, Motoo Araki, Ryuta Tanimoto, Takuya Sadahira, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Hirochika Nakajima, Herik Acosta, Satoshi Katayama, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    BMC urology   21 ( 1 )   45 - 45   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12894-021-00819-2

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  • Pancreas preservation in extracellular-type p38 inhibitor-containing solution improves islet yield for porcine islet isolation. 国際誌

    Tasuku Yonaha, Chika Miyagi-Shiohira, Kazuho Kuwae, Yoshihito Tamaki, Kai Nishime, Mayuko Sakai-Yonaha, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    Xenotransplantation   28 ( 2 )   e12661   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/xen.12661

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  • Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors. 国際誌

    Chika Miyagi-Shiohira, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    Journal of clinical medicine   10 ( 3 )   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/jcm10030454

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  • The role of Wnt signaling in male reproductive physiology and pathology. 国際共著 国際誌

    Ruizhi Xue, Wenfeng Lin, Jingkai Sun, Masami Watanabe, Abai Xu, Motoo Araki, Yasutomo Nasu, Zhengyan Tang, Peng Huang

    Molecular human reproduction   27 ( 1 )   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/molehr/gaaa085

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  • The role of Wnt signaling in male reproductive physiology and pathology. 国際誌

    Ruizhi Xue, Wenfeng Lin, Jingkai Sun, Masami Watanabe, Abai Xu, Motto Akira, Yasutomo Nasu, Zhengyan Tang, Peng Huang

    Molecular human reproduction   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/molehr/gaaa085

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  • Long-term ureteroscopic management of upper tract urothelial carcinoma: 28-year single-centre experience. 国際誌

    Yuki Maruyama, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yosuke Mitsui, Takuya Sadahira, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Manoj Monga, Yasutomo Nasu, Hiromi Kumon

    Japanese journal of clinical oncology   51 ( 1 )   130 - 137   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/jjco/hyaa132

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  • Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment. 国際共著 国際誌

    Wenfeng Lin, Chaoming Li, Naijin Xu, Masami Watanabe, Ruizhi Xue, Abai Xu, Motoo Araki, Ruifen Sun, Chunxiao Liu, Yasutomo Nasu, Peng Huang

    International journal of nanomedicine   16   2775 - 2787   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2147/IJN.S301552

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  • Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer. 国際共著 国際誌

    Wenfeng Lin, Jingkai Sun, Takuya Sadahira, Naijin Xu, Koichiro Wada, Chunxiao Liu, Motoo Araki, Abai Xu, Masami Watanabe, Yasutomo Nasu, Peng Huang

    International journal of biological sciences   17 ( 12 )   3255 - 3267   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.7150/ijbs.63125

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  • A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial.

    Takuya Sadahira, Yuki Maruyama, Yoshiki Hiyama, Hiroyuki Kitano, Hiroki Yamada, Takayuki Goto, Tsubasa Kondo, Katsumi Shigemura, Yosuke Mitsui, Takehiro Iwata, Kohei Edamura, Motoo Araki, Masami Watanabe, Tadasu Takenaka, Jun Teishima, Yasuyoshi Miyata, Kiyohito Ishikawa, Ei-Ichiro Takaoka, Jun Miyazaki, Satoshi Takahashi, Naoya Masumori, Hiroshi Kiyota, Masato Fujisawa, Shingo Yamamoto, Takafumi Sakuma, Norihiro Kusumi, Takaharu Ichikawa, Toyohiko Watanabe, Yoshitsugu Nasu, Masaya Tsugawa, Yasutomo Nasu, Koichiro Wada

    Acta medica Okayama   75 ( 5 )   663 - 667   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/62782

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  • Novel canine isocitrate dehydrogenase 1 mutation Y208C attenuates dimerization ability. 国際誌

    Shota Kawakami, Masaki Michishita, Motoharu Sakaue, Masami Morimatsu, Mitsuki Uemura, Nobuaki Kashiwagi, Marika Maeda, Yukino Machida, Daigo Azakami, Ai S Egusa, Eri Onozawa, Katsumi Ishioka, Masami Watanabe, Yoshikazu Tanaka, Toshinori Omi, Kazuhiko Ochiai

    Oncology letters   20 ( 6 )   351 - 351   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/ol.2020.12214

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  • Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection. 国際誌

    Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Haruhito Adam Uchida, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    International journal of urology : official journal of the Japanese Urological Association   27 ( 12 )   1136 - 1142   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/iju.14382

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  • Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function. 国際誌

    Kai Nishime, Chika Miyagi-Shiohira, Kazuho Kuwae, Yoshihito Tamaki, Tasuku Yonaha, Mayuko Sakai-Yonaha, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons   21 ( 8 )   2698 - 2708   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/ajt.16401

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  • Kyoto probe-1 reveals phenotypic differences between mouse ES cells and iTS-P cells. 国際誌

    Chika Miyagi-Shiohira, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    Scientific reports   10 ( 1 )   18084 - 18084   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-020-75016-6

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  • Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes. 国際誌

    The Mon La, Hiromi Tachibana, Shun-Ai Li, Tadashi Abe, Sayaka Seiriki, Hikaru Nagaoka, Eizo Takashima, Tetsuya Takeda, Daisuke Ogawa, Shin-Ichi Makino, Katsuhiko Asanuma, Masami Watanabe, Xuefei Tian, Shuta Ishibe, Ayuko Sakane, Takuya Sasaki, Jun Wada, Kohji Takei, Hiroshi Yamada

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   34 ( 12 )   16449 - 16463   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1096/fj.202001240RR

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  • Internalization of AMPA-type Glutamate Receptor in the MIN6 Pancreatic β-cell Line. 査読

    The Mon La, Hiroshi Yamada, Sayaka Seiriki, Shun-Ai Li, Kenshiro Fujise, Natsuho Katsumi, Tadashi Abe, Masami Watanabe, Kohji Takei

    Cell structure and function   45 ( 2 )   121 - 130   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1247/csf.20020

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  • Mutations in the C1 element of the insulin promoter lead to diabetic phenotypes in homozygous mice. 国際誌

    Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima, Takao Kinjo, Issei Saitoh, Masami Watanabe

    Communications biology   3 ( 1 )   309 - 309   2020年6月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s42003-020-1040-z

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  • Dkk3/REIC, an N-glycosylated Protein, Is a Physiological Endoplasmic Reticulum Stress Inducer in the Mouse Adrenal Gland.

    Hirofumi Fujita, Tetsuya Bando, Seiichi Oyadomari, Kazuhiko Ochiai, Masami Watanabe, Hiromi Kumon, Hideyo Ohuchi

    Acta medica Okayama   74 ( 3 )   199 - 208   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/59950

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  • Tumor suppressor REIC/Dkk‑3 and its interacting protein SGTA inhibit glucocorticoid receptor to nuclear transport 査読

    Takehiro Iwata, Takuya Sadahira, Kazuhiko Ochiai, Hideo Ueki, Takanori Sasaki, Peng Haung, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu, Masami Watanabe

    Experimental and Therapeutic Medicine   2020年5月

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/etm.2020.8819

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  • Correlation between lumbar skeletal muscle size and urinary incontinence after radical prostatectomy. 査読 国際誌

    Yosuke Mitsui, Takuya Sadahira, Toyohiko Watanabe, Motoo Araki, Yuki Maruyama, Ryota Sato, Acosta Gonzalez, Herik Rodrigo, Koichiro Wada, Masami Watanabe, Michael B Chancellor, Yasutomo Nasu

    Lower urinary tract symptoms   12 ( 3 )   245 - 252   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/luts.12312

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  • Novel cell-permeable p38-MAPK inhibitor efficiently prevents porcine islet apoptosis and improves islet graft function. 国際誌

    Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima, Issei Saitoh, Masami Watanabe

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons   20 ( 5 )   1296 - 1308   2020年5月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/ajt.15740

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  • Factors predicting pathological upgrading after prostatectomy in patients with Gleason grade group 1 prostate cancer based on opinion-matched biopsy specimens. 査読 国際誌

    Yuki Maruyama, Takuya Sadahira, Motoo Araki, Yosuke Mitsui, Koichiro Wada, Acosta Gonzalez, Herik Rodrigo, Kazuaki Munetomo, Yasuyuki Kobayashi, Masami Watanabe, Hiroyuki Yanai, Toyohiko Watanabe, Yasutomo Nasu

    Molecular and clinical oncology   12 ( 4 )   384 - 389   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/mco.2020.1996

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  • Quality of Life and Mental Satisfaction Improve Slowly in Preemptive Kidney Transplantation Compared With Nonpreemptive Kidney Transplantation. 査読 国際誌

    Yosuke Mitsui, Motoo Araki, Yuki Maruyama, Kasumi Yoshinaga, Takuya Sadahira, Koichiro Wada, Katsuyuki Tanabe, Masashi Kitagawa, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Transplantation proceedings   52 ( 3 )   740 - 747   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.transproceed.2020.01.042

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  • Robotic Renal Autotransplantation: A Feasibility Study in a Porcine Model. 査読

    Risa Kubota, Motoo Araki, Koichiro Wada, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Yuichi Ariyoshi, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Yuzuki Kano, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Acta medica Okayama   74 ( 1 )   53 - 58   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/57953

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  • Promising Gene Therapy Using an Adenovirus Vector Carrying REIC/Dkk-3 Gene for the Treatment of Biliary Cancer. 査読 国際誌

    Emi Tanaka, Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Atsushi Ohyama, Masaya Iwamuro, Masami Watanabe, Hiromi Kumon, Hiroyuki Okada

    Current gene therapy   20 ( 1 )   64 - 70   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2174/1566523220666200309125709

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  • Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity. 国際共著 国際誌

    Naijin Xu, Wenfeng Lin, Jingkai Sun, Takuya Sadahira, Abai Xu, Masami Watanabe, Kai Guo, Motoo Araki, Gonghui Li, Chunxiao Liu, Yasutomo Nasu, Peng Huang

    Journal of Cancer   11 ( 22 )   6633 - 6641   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.7150/jca.47025

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  • Clinical pharmacokinetics of oral azithromycin in epididymal tissue. 査読 国際誌

    Sadahira T, Wada K, Ikawa K, Morikawa N, Mitsui M, Araki M, Fujiyoshi M, Ishii A, Watanabe M, Watanabe T, Nasu Y

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 10 )   832 - 834   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jiac.2019.05.011

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  • Excellent Islet Yields after 18-h Porcine Pancreas Preservation by Ductal Injection, Pancreas Preservation with MK Solution, Bottle Purification, and Islet Purification Using Iodixanol with UW Solution and Iodixanol with MK Solution. 査読 国際誌

    Kuwae K, Miyagi-Shiohira C, Hamada E, Tamaki Y, Nishime K, Sakai M, Yonaha T, Makishi E, Saitoh I, Watanabe M, Noguchi H

    Journal of clinical medicine   8 ( 10 )   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/jcm8101561

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  • The canine RAD51 mutation leads to the attenuation of interaction with PALB2. 査読 国際誌

    Uemura M, Ochiai K, Morimatsu M, Michishita M, Onozawa E, Azakami D, Uno Y, Yoshikawa Y, Sasaki T, Watanabe M, Omi T

    Veterinary and comparative oncology   18 ( 2 )   247 - 255   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/vco.12542

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  • Comparison of the predictive value among inflammation-based scoring systems for bleomycin pulmonary toxicity in patients with germ cell tumors. 査読 国際誌

    Maruyama Y, Sadahira T, Araki M, Mitsui Y, Wada K, Edamura K, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

    International journal of urology : official journal of the Japanese Urological Association   26 ( 8 )   813 - 819   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/iju.14017

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  • Comparison of longitudinal health-related quality-of-life outcomes between anterior and posterior surgical approaches to robot-assisted radical prostatectomy. 査読 国際誌

    Maruyama Y, Sadahira T, Araki M, Mitsui Y, Wada K, Tanimoto R, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

    Journal of robotic surgery   14 ( 2 )   255 - 260   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s11701-019-00975-6

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  • Identification of Proteins Differentially Expressed by Adipose-derived Mesenchymal Stem Cells Isolated from Immunodeficient Mice. 査読 国際誌

    Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Kitamura S, Saitoh I, Watanabe M, Fujita J, Noguchi H

    Int J Mol Sci   20 ( 11 )   E2672   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms20112672

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  • Upregulation of mobility in pancreatic cancer cells by secreted S100A11 through activation of surrounding fibroblasts. 査読 国際誌

    Mitsui Y, Tomonobu N, Watanabe M, Kinoshita R, Sumardika W, Youyi C, Murata H, Yamamoto KI, Sadahira T, Rodrigo AGH, Takamatsu H, Araki K, Yamauchi A, Yamamura M, Fujiwara H, Inoue Y, Futami J, Saito K, Iioka H, Kondo E, Nishibori M, Toyooka S, Yamamoto Y, Nasu Y, Sakaguchi M

    Oncology research   27 ( 8 )   945 - 956   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3727/096504019X15555408784978

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  • A Novel Preservation Solution Containing a JNK Inhibitory Peptide Efficiently Improves Islet Yield for Porcine Islet Isolation. 査読 国際誌

    Noguchi H, Miyagi-Shiohira C, Nakashima Y, Ebi N, Hamada E, Tamaki Y, Kuwae K, Kitamura S, Kobayashi N, Saitoh I, Watanabe M

    Transplantation   103 ( 2 )   344 - 352   2019年2月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/TP.0000000000002555

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  • A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of Primary Cultured Cells and Subcultured Cells Using Mouse Adipose-Derived Mesenchymal Stem Cells. 査読 国際誌

    Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Saitoh I, Watanabe M, Fujita J, Noguchi H

    Stem Cells Int   2019   7274057 - 7274057   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2019/7274057

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  • Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors. 査読

    Noguchi H, Miyagi-Shiohira C, Nakashima Y, Kinjo T, Kobayashi N, Saitoh I, Watanabe M, Shapiro AMJ, Kin T

    Mol Ther Methods Clin Dev   13   243 - 252   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • The Novel Combination of Nitroxoline and PD-1 Blockade, Exerts a Potent Antitumor Effect in a Mouse Model of Prostate Cancer. 査読 国際共著 国際誌

    Naijin Xu, Linglong Huang, Xiezhao Li, Masami Watanabe, Chaoming Li, Abai Xu, Chunxiao Liu, Qiang Li, Motoo Araki, Koichiro Wada, Yasutomo Nasu, Peng Huang

    International journal of biological sciences   15 ( 5 )   919 - 928   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.7150/ijbs.32259

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  • Pelvic magnetic resonance imaging parameters predict urinary incontinence after robot-assisted radical prostatectomy. 査読 国際誌

    Sadahira T, Mitsui Y, Araki M, Maruyama Y, Wada K, Edamura K, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

    Lower urinary tract symptoms   11 ( 3 )   122 - 126   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/luts.12245

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  • Burned-out Prostate Cancer ? Primary Metastatic Cancer Not Detected on Repeat Biopsy. 査読

    Mitsui Y, Sadahira T, Maruyama Y, Wada K, Tanimoto R, Sugimoto M, Araki M, Watanabe M, Yanai H, Watanabe T, Nasu Y

    Acta medica Okayama   72 ( 6 )   605 - 609   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/56380

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  • The 3-D Volumetric Measurement Including Resected Specimen for Predicting Renal Function AfterRobot-assisted Partial Nephrectomy. 査読 国際誌

    Mitsui Y, Sadahira T, Araki M, Maruyama Y, Nishimura S, Wada K, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

    Urology   125   104 - 110   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.urology.2018.12.020

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  • A Comparison of Proteins Expressed between Human and Mouse Adipose-Derived Mesenchymal Stem Cells by a Proteome Analysis through Liquid Chromatography with Tandem Mass Spectrometry. 査読

    Nahar S, Nakashima Y, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Saitoh I, Watanabe M, Noguchi H, Fujita J

    Int J Mol Sci   19 ( 11 )   E3497   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Cytokines in adipose-derived mesenchymal stem cells promote the healing of liver disease. 査読

    Nahar S, Nakashima Y, Miyagi-Shiohira C, Kinjo T, Toyoda Z, Kobayashi N, Saitoh I, Watanabe M, Noguchi H, Fujita J

    World J Stem Cells   10 ( 11 )   146 - 159   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Loss of psoas major muscle volume during systemic chemotherapy is related to worse prognosis in testicular cancer. 査読 国際誌

    Mitsui Y, Sadahira T, Araki M, Maruyama Y, Wada K, Tanimoto R, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

    Japanese journal of clinical oncology   49 ( 2 )   183 - 189   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/jjco/hyy166

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  • Induction of Expandable Adipose-Derived Mesenchymal Stem Cells from Aged Mesenchymal Stem Cells by a Synthetic Self-Replicating RNA. 査読

    Miyagi-Shiohira C, Nakashima Y, Kobayashi N, Kitamura S, Saitoh I, Watanabe M, Noguchi H

    Int J Mol Sci   19 ( 11 )   E3489   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Red nodular melanoma of the penile foreskin: A case report and literature review. 査読 国際誌

    Maruyama Y, Sadahira T, Mitsui Y, Wada K, Tanimoto R, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y

    Molecular and clinical oncology   9 ( 4 )   449 - 452   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/mco.2018.1697

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  • A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of the Proteins Secreted by Human Adipose-Derived Mesenchymal Stem Cells. 査読

    Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Toyoda Z, Kobayashi N, Saitoh I, Watanabe M, Fujita J, Noguchi H

    Cell Transplant   27 ( 10 )   1469 - 1494   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A Comparison of the Preservation of Mouse Adipose Tissue-Derived Mesenchymal Stem Cells Using the University of Wisconsin Solution and Hank's Balanced Salt Solution. 査読

    Nahar S, Nakashima Y, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Saitoh I, Watanabe M, Noguchi H, Fujita J

    Stem Cells Int   2018   1625464   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway. 査読 国際誌

    Jinlin Xie, Wenfeng Lin, Linglong Huang, Naijin Xu, Abai Xu, Binshen Chen, Masami Watanabe, Chunxiao Liu, Peng Huang

    Oncology letters   16 ( 3 )   3867 - 3873   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bufalin, one of the active ingredients of the Chinese drug Chan su, exhibits significant antitumor activity against various cancer types. However, the role of bufalin in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that bufalin inhibited cell proliferation, blocked the cell cycle in the G2/M phase, and reduced the metastasis of human RCC ACHN cells via the upregulation of p21waf/cip1 and E-cadherin and the downregulation of cyclin dependent kinase 1, cyclin B1, N-cadherin, and hypoxia-inducible factor-1α (HIF-1α). Further mechanistic study revealed that bufalin reduced the expression of phosphorylated (phospho)-Akt and phospho-mammalian target of rapamycin (mTOR). Moreover, HIF-1α expression may be regulated through the inhibition of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR signaling pathway. Thus, the present results suggest that bufalin induces cell cycle arrest and suppresses metastasis; this process may be associated with the PI3K/Akt/mTOR signaling pathway. Accordingly, it is suggested that bufalin is a therapeutic agent for RCC.

    DOI: 10.3892/ol.2018.9111

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  • Clinical impact of abdominal fat distribution measured by 3-D computed tomography volumetry on post-transplant renal function in recipients after living kidney transplantation: a retrospective study. 査読

    Mitsui Y, Sadahira T, Araki M, Maruyama Y, Wada K, Tanimoto R, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

    Clinical and experimental nephrology   23 ( 3 )   415 - 424   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10157-018-1643-6

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  • 排尿障害を伴う女性尿道憩室に対して手術治療を行った1例

    松尾 聡子, 杉本 盛人, 佐久間 貴文, 坪井 一朗, 本郷 智拡, 三井 將雄, 河村 香澄, 和田里 章悟, 丸山 雄樹, 光井 洋介, 定平 卓也, 前原 貴典, 大岩 裕子, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 谷本 竜太, 小林 泰之, 荒木 元朗, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友, 中村 あや, 津島 知靖

    西日本泌尿器科   80 ( 9 )   495 - 495   2018年9月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 前立腺に発生したSFT(Solitary fibrous tumor)の1例

    本郷 智拡, 高本 篤, 三井 將雄, 松尾 聡子, 坪井 一朗, 佐久間 貴文, 和田里 章悟, 河村 香澄, 丸山 雄樹, 光井 洋介, 前原 貴典, 窪田 理沙, 大岩 裕子, 定平 卓也, 西村 慎吾, 佐古 智子, 和田 耕一郎, 谷本 竜太, 杉本 盛人, 小林 泰之, 石井 亜矢乃, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   80 ( 9 )   497 - 497   2018年9月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • Comparison Between Modified Extracellular-Type Trehalose-Containing Kyoto Solution and University of Wisconsin Solution in 18-Hour Pancreas Preservation for Islet Transplantation. 査読

    Hamada E, Ebi N, Miyagi-Shiohira C, Tamaki Y, Nakashima Y, Kobayashi N, Saitoh I, Watanabe M, Kinjo T, Noguchi H

    Pancreas   47 ( 7 )   e46 - e47   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA. 査読

    Miyagi-Shiohira C, Nakashima Y, Kobayashi N, Saitoh I, Watanabe M, Noguchi H

    Sci Rep   8 ( 1 )   12341   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line 査読

    Kazuhiko Ochiai, Daigo Azakami, Masami Morimatsu, Hinako Hirama, Shota Kawakami, Takayuki Nakagawa, Masaki Michishita, Ai S. Egusa, Takanori Sasaki, Masami Watanabe, Toshinori Omi

    Oncology Reports   40 ( 1 )   488 - 494   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Spandidos Publications  

    Mutations in the p53 gene are associated with more than half of all human cancers. These mutations often cause a disruption of the tumor-suppressor function of p53 and induce genomic instabilities. Wild-type p53 requires tetramerization to function as an initiator of cell cycle arrest and apoptosis. Although alterations in p53 tetramerization caused by mutation have been well studied, there are few cell lines containing an endogenous mutation in the tetramerization domain of p53. Here, we report the discovery of a canine mammary gland tumor cell line CTB-m2, which contains the Leu332Gln (L332Q) mutation corresponding to Leu344 in the tetramerization domain of human p53. Although CTB-m2 cells are genetically heterozygous for the Leu332Gln mutation, the mutant mRNA was almost exclusively expressed. CTB-m2 cells showed enhanced cell proliferation compared to wild-type p53-expressing CTB-m cells of the same lineage. A p53 tetramerization reporter assay showed that the ability of the p53 mutant to form tetramers was signifcantly lower than that of wild-type p53. An immunoblot analysis of cross-linked p53 oligomerized forms demonstrated that the L332Q mutant lacked the ability to form tetramers but retained the ability to form dimers. These data suggest that the p53 mutant cell line CTB-m2 could be a useful tool for analyzing the precise tetramerization mechanisms of p53 and verifying the effects of therapeutic agents against tumors expressing p53 mutants that lack the ability to tetramerize.

    DOI: 10.3892/or.2018.6409

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  • Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation. 査読

    Noguchi H, Miyagi-Shiohira C, Nakashima Y, Ebi N, Hamada E, Tamaki Y, Kuwae K, Kobayashi N, Saitoh I, Watanabe M

    Sci Rep   8 ( 1 )   11082   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-018-29481-9

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  • A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of Cells Cultured in DMEM 10% FBS and Chemically Defined Medium Using Human Adipose-Derived Mesenchymal Stem Cells. 査読

    Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Saitoh I, Watanabe M, Fujita J, Noguchi H

    Int J Mol Sci   19 ( 7 )   E2042   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 新規抗癌免疫療法としてのAd-REIC遺伝子治療とその臨床効果

    定平 卓也, 渡部 昌実, 那須 保友

    日本がん免疫学会総会プログラム・抄録集   22回   69 - 69   2018年7月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • 膵がん進展に導く膵がん細胞 間質線維芽細胞クロストークを介在する分泌性S100A11 受容体RAGE連携の役割

    光井 洋介, 山本 健一, Sumardika I Wayan, 木下 理恵, 村田 等, 二見 淳一郎, 高松 仁, 山本 靖彦, 西堀 正洋, 豊岡 伸一, 渡部 昌実, 那須 保友, 阪口 政清

    日本がん免疫学会総会プログラム・抄録集   22回   156 - 156   2018年7月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with germ cell tumors 査読

    Yuki Maruyama, Takuya Sadahira, Yosuke Mitsui, Motoo Araki, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Medical Oncology   35 ( 6 )   80   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Humana Press Inc.  

    Bleomycin pulmonary toxicity (BPT) has been well described in patients with germ cell tumors treated with bleomycin etoposide and cisplatin chemotherapy (BEP). To assess the prognostic impact of BPT, we retrospectively identified 52 patients who underwent bleomycin etoposide and cisplatin chemotherapy from 2008 to 2017 in our institution, and evaluated the risk factors of BPT and its effect on prognosis. Patients who had received chemotherapy at another institution were excluded. BPT was defined as bleomycin discontinuation in response to pulmonary function test decline, pulmonary symptoms, or interstitial pneumonia on computed tomography without infection. We divided the patients into two groups according to this definition: BPT and non-BPT. Their median age was 34.2 years, and their median body mass index was 22.8 kg/m2. Twenty patients had a smoking history, 37 were diagnosed with non-seminoma, and 20 had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified into the BPT group and 37 into the non-BPT group. Only body mass index &lt
    22 was identified as a predictor of BPT in multivariable logistic models. Age or use of granulocyte-colony stimulating factor did not have a significant impact. Kaplan–Meier analysis revealed that the presence of BPT had no significant impact on either 5-year overall survival or progression-free survival. Lower body mass index can increase the risk of BPT in patients with germ cell tumors undergoing BEP. However, discontinuation of bleomycin with BPT does not adversely influence the survival outcomes.

    DOI: 10.1007/s12032-018-1140-5

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  • The Development of Cancer through the Transient Overexpression of Reprogramming Factors 査読

    Miyagi-Shiohira Chika, Nakashima Yoshiki, Kobayashi Naoya, Saitoh Issei, Watanabe Masami, Noguchi Yasufumi, Kinjo Takao, Noguchi Hirofumi

    CELL MEDICINE   10   2018年5月

  • Role of Egr1 on Pancreatic Endoderm Differentiation 査読

    Tsugata Takako, Nikoh Naruo, Kin Tatsuya, Miyagi-Shiohira Chika, Nakashima Yoshiki, Saitoh Issei, Noguchi Yasufumi, Ueki Hideo, Watanabe Masami, Kobayashi Naoya, Shapiro Andrew, M. James, Noguchi Hirofumi

    CELL MEDICINE   10   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Adhesion characteristics of porcine pancreatic islets and exocrine tissue to coating materials 査読

    Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    Islets   10 ( 3 )   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Taylor and Francis Inc.  

    Since the report of the Edmonton protocol in 2000, islet transplantation has been implemented worldwide, and xenotransplantation using porcine islets has also been reported. In addition, many basic experiments using pancreatic islets and exocrine tissue after isolation have been reported. Recently, exocrine cells have been found to be essential for inducing the differentiation of pancreatic islets. Therefore, the importance of the culture conditions for pancreatic tissue when conducting experiments using pancreatic tissue is also increasing. In this study, we focused on the coat material and examined the adhesive properties of porcine pancreatic islets and exocrine tissue after isolation. Porcine islet isolation was performed, and isolated islets (purity ≥95%) and exocrine tissue (purity ≥99%) were used to achieve adhesion to several extracellular matrixes, fibronectin, collagen type I, collagen type IV, laminin I, fibrinogen, and bovine serum albumin (BSA). DMEM with 0.5% FBS was used as the assay medium. For exocrine tissue, the adhesion was promoted in fibronectin, collagen type I, laminin I, and fibrinogen. The adhesive ability to fibronectin was more than twice that to BSA, while the adhesive ability to collagen type I, laminin I, and fibrinogen was less than twice that to BSA. For islets, the adhesive ability to fibronectin was weaker than that of exocrine tissue. Furthermore, the adhesion effect in fibronectin was obtained within 30 minutes and in medium containing little serum for both islets and exocrine tissues. These data suggest that fibronectin may be useful for the adhesion of pancreatic tissue.

    DOI: 10.1080/19382014.2018.1460294

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  • Programmed death ligand 1 expression in bladder. 査読

    Peng Zhou, Qiongren Wang, Chongshan Wang, Xiezhao L, Wei Du, Chunxiao Liu, Masami Watanabe, Peng Huang, Abai Xu

    Int J Clin Exp Pathol   2018年4月

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    記述言語:英語  

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  • R132 mutations in canine isocitrate dehydrogenase 1 (IDH1) lead to functional changes 査読

    Shota Kawakami, Kazuhiko Ochiai, Daigo Azakami, Yuiko Kato, Masaki Michishita, Masami Morimatsu, Toshina Ishiguro-Oonuma, Eri Onozawa, Masami Watanabe, Toshinori Omi

    Veterinary Research Communications   42 ( 1 )   49 - 56   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Netherlands  

    Glioma is the second most common intracranial neoplasia in dogs, but the pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 1 (IDH1) is frequently mutated in gliomas. Although almost all human IDH1 mutations have been identified as involving the Arg132 codon, few studies have reported structural, functional, and mutational information for canine IDH1. Therefore, in this study, we cloned the canine IDH1 homologue and used PCR mutagenesis to substitute the wildtype (WT) Arg132 with His (R132H) or Ser (R132S). WT and mutated IDH1 were overexpressed in HeLa cells, and their presence was confirmed by immunoblotting and immunocytochemistry using mutation-specific antibodies. The IDH1 activity between WT, R132H, and R132S transfectants was compared by measuring the production of NADH and NADPH. NADPH production in R132H and R132S transfectants was lower than that in WT, but NADH levels were not significantly different. Finally, we detected increased expression of hypoxia inducible factor 1 alpha (HIF-1α) in the R132H and R132S transfectants. These results indicated that the canine IDH1 Arg132 mutation has the potential to induce carcinogenesis in canine somatic cells.

    DOI: 10.1007/s11259-017-9707-8

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  • Induction of cells with prostate cancer stem-like properties from mouse induced pluripotent stem cells via conditioned medium. 査読 国際誌

    Naijin Xu, Xiezhao Li, Masami Watanabe, Hideo Ueki, Hao Hu, Na Li, Motoo Araki, Koichiro Wada, Abai Xu, Chunxiao Liu, Yasutomo Nasu, Peng Huang

    American journal of cancer research   8 ( 8 )   1624 - 1632   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent stem cells (miPSCs) into prostate cancer stem-like cells with carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9, a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM, displayed CSCs properties, including spheroids morphology and expression of both stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44, and CD133. In addition, in vivo transplantation experiment was performed to confirm the tumorigenicity. Furthermore, we used the model to assess conventional chemotherapeutic agent, docetaxel. The results showed that miPS-RM9CM cells exhibited increased resistance to docetaxel, however, high susceptibility to the cancer cell stemness inhibitor I (BBI-608). Our current study demonstrates that CM from cultured RM9 cells play a crucial role in the determination of cell fate from miPSCs to cancer stem-like cells and provide a potentially valuable system for the study of CSCs.

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  • Glaucocalyxin A induces G2/M cell cycle arrest and apoptosis through the PI3K/Akt pathway in human bladder cancer cells. 査読 国際誌

    Wenfeng Lin, Jinlin Xie, Naijin Xu, Linglong Huang, Abai Xu, Hulin Li, Chaoming Li, Yubo Gao, Masami Watanabe, Chunxiao Liu, Peng Huang

    International journal of biological sciences   14 ( 4 )   418 - 426   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glaucocalyxin A (GLA), a major component isolated from Rabdosia japonica, has been proven to show anti-bacterial and anti-tumor biological characteristics according to previous studies. However, its potential effect on bladder cancer remains unknown. The present research aims to investigate the underlying mechanism in treating bladder cancer in vivo and in vitro. Cell proliferation was analyzed by CCK-8 assay and colony formation. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of the cell cycle and apoptosis-related proteins were detected by western blotting and immunofluorescence staining. Meanwhile, the in vivo study was performed to evaluate the anti-tumor effect on a UMUC3 subcutaneous tumor of NOD/SCID mice model. GLA suppressed colony-formation ability, triggered G2/M arrest and promoted apoptosis of UMUC3 cells in a dose-dependent manner. Furthermore, western blotting showed that GLA downregulated the expressions of PI3K p85, p-Akt, Bcl-2, CDK1, Cyclin B1 whereas upregulated the levels of PTEN, Bax, Cleaved Caspase-3. In vivo, GLA at a dosage of 20 mg/kg significantly inhibited tumor growth compared with the control group by intraperitoneal injection. These results suggested that GLA-related G2/M arrest and apoptosis in UMUC3 cells were mediated by a suppressed PI3K/Akt signaling pathway, which regulated p21Waf1/Cip1 as well as intrinsic caspase cascade. Collectively, our observations could help to develop new drugs targeting the PI3K/Akt pathway for the treatment of bladder cancer.

    DOI: 10.7150/ijbs.23602

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  • Functional alteration of canine isocitrate dehydrogenase 2 (IDH2) via an R174K mutation 査読

    Shota Kawakami, Kazuhiko Ochiai, Yuiko Kato, Masaki Michishita, Hinako Hirama, Ryo Obara, Daigo Azakami, Masami Watanabe, Toshinori Omi

    Journal of Veterinary Medical Science   80 ( 1 )   85 - 91   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Veterinary Science  

    Gliomas are common intracranial neoplasias in dogs. However, the underlying pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 2 (IDH2) is often mutated in gliomas. Although almost human IDH2 mutations have been identified at the Arg172 codon, few studies have reported structural, functional or mutational information for canine IDH2. In this study, we cloned the full-length canine IDH2 (cIDH2) cDNA and substituted wild type Arg174 (cIDH2 WT: corresponding to R172 of human IDH2) with Lys (cIDH2 R174K). The cIDH2 WT and R174K proteins were overexpressed in HeLa cells, and their presence was confirmed using an anti-human IDH2-WT mAb (clone: KrMab-3) and an anti-IDH2-R172K mAb (clone: KMab-1). The IDH2 activity between cIDH2 WT and cIDH2 R174K transfectants was compared by measuring the production of NADH and NADPH. NADPH production was lower for cIDH2 R174K than that for cIDH2 WT transfectants. Finally, we detected increased expression of hypoxia inducible factor-1 alpha (HIF-1α) in cIDH2 R174K transfectants. This indicates that mutations at R174 can potentially induce carcinogenesis in canine somatic cells.

    DOI: 10.1292/jvms.17-0362

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  • Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk-3) 査読

    K. Ochiai, H. Oda, S. Shono, Y. Kato, S. Sugihara, S. Nakazawa, D. Azakami, M. Michishita, E. Onozawa, M. Bonkobara, T. Sako, L. Shun-Ai, H. Ueki, M. Watanabe, T. Omi

    VETERINARY AND COMPARATIVE ONCOLOGY   15 ( 4 )   1181 - 1186   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Reduced expression in immortalized cells (REIC/Dkk-3), a member of the human Dickkopf (Dkk) family, is a growth suppressor in human and canine mammary tumours. Mammary gland tumours are common neoplasms with high malignancy in female cats. The purpose of this study was to clone the feline REIC/Dkk-3 homolog, investigate its expression in cell lines established from feline mammary gland tumours, and test its tumour suppressor function. Western blot analysis revealed that expression of the REIC/Dkk-3 protein was reduced in feline mammary carcinoma cell lines. Forced expression of REIC/Dkk-3 induced apoptosis in feline mammary tumour cell lines. These results demonstrate that REIC/Dkk-3 expression, which is downregulated in feline mammary tumour cell lines, results in the induction of apoptosis in these cells. Our findings suggest that feline REIC/Dkk-3 represents a potential molecular target for the development of therapies against feline mammary cancers.

    DOI: 10.1111/vco.12254

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  • Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK1. 査読

    Xu J, Sadahira T, Kinoshita R, Li S, Huang P, Wada K, Araki M, Ochiai K, Noguchi H, Sakaguchi M, Nasu Y, Watanabe M

    Oncol Lett   14 ( 5 )   5638 - 5642   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/ol.2017.6833

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  • Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma 査読

    Hiroaki Sawahara, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Ryo Kato, Atsushi Oyama, Teruya Nagahara, Masaya Iwamuro, Shigeru Horiguchi, Koichiro Tsutsumi, Mari Mandai, Tetsushige Mimura, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Masami Watanabe, Masakiyo Sakaguchi, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   32 ( 10 )   1769 - 1777   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Background and Aim: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.
    Methods: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.
    Results: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).
    Conclusions: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

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  • Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells 査読

    Yuhei Horikawa, Masami Watanabe, Takuya Sadahirai, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Koichiro Wada, Kazuhiko Ochiai, Shun-Ai Li, Yasutomo Nasu

    ONCOLOGY LETTERS   14 ( 3 )   3223 - 3228   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated. Treatment with Ad-REIC markedly downregulated the expression of CD147 and significantly inhibited cellular proliferation. Since the expression of CD147 is reported to be under the positive control of mitogen-activated protein kinase (MAPK) signaling and the c-Myc protein, the correlations between the expression of CD147 and the activation of MAPKs or the expression of c-Myc were examined. Unexpectedly, no positive correlation was observed between the level of CD147 and the potential regulators that were assessed, indicating that another signaling pathway is responsible for the downregulation of CD147. The results from the present study demonstrate that Ad-REIC treatment can significantly downregulate the expression of CD147 in bladder cancer cells. Downregulation of the cancer-progression factor CD147 may be a novel mechanism that underlies the therapeutic effects of Ad-REIC treatment.

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  • Robotic Renal Autotransplantation: First Case Outside of North America 査読

    Motoo Araki, Koichiro Wada, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Takashi Yoshioka, Yuichi Ariyoshi, Kei Fujio, Atsushi Takamoto, Morito Sugimoto, Katsumi Sasaki, Yasuyuki Kobayashi, Shin Ebara, Hideki Taninishi, Hiroyuki Amano, Masashi Inui, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    ACTA MEDICA OKAYAMA   71 ( 4 )   351 - 355   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    A 38-year-old woman with a 2.7-cm left ureteral stenosis requiring chronic ureteral stent exchange elected to undergo robotic renal autotransplantation. Left ureteropelvic junction obstruction (UPJO) was also suspected. Robotic donor nephrectomy contributed to the fine dissection for desmoplastic changes. The kidney was removed through a Gelport and examined on ice. UPJO was not seen. An end-to-side robotic anastomosis was created between the renal and external iliac vessels. The console time was 507 min, and the warm ischemia time was 4 min 5 sec. She became stent-free. Robotic renal autotransplantation is a new, minimally invasive approach to renal preservation.

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  • Robust cancer-specific gene expression by a novel cassette with hTERT and CMV promoter elements 査読

    Masakiyo Sakaguchi, Takuya Sadahira, Hideo Ueki, Rie Kinoshita, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Yasutomo Nasu, Kazuhiko Ochiai, Hiromi Kumon, Nam-Ho Huh, Masami Watanabe

    ONCOLOGY REPORTS   38 ( 2 )   1108 - 1114   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    We developed and validated a novel hTERT/CMV promoter element-driven gene expression cassette that can robustly enhance cancer-specific gene expression. The following gene expressional elements were located in tandem within the plasmid construct: [hTERT core promoter, cytomegalovirus (CMV) minimized promoter, RU5' sequence, an inserted gene, BGH polyA, hTERT enhancer]; this is hereafter referred to as the hT/Cm-R-hT construct. Using various human cancer cell lines and normal cells, the cancer-specific transcription of the green fluorescent protein (GFP) gene was examined by western blotting and fluorescence microscopy. Cancer-specific gene expression was robustly achieved in the hT/Cm-R-hT plasmid in comparison to the other control hT/Cm-driven construct. Notably, the expression level of GFP observed in the hT/Cm-RhT-driven construct was superior to that of the control plasmid with the conventional CMV promoter in HEK293 cells, which are known to possess higher hTERT activity than normal cells. We next examined the availability of hT/Cm-R-hT in detecting the target GFP expressing cancer cells from human peripheral blood mononuclear cells (PBMCs). The hT/Cm-R-hT plasmid successfully induced cancer-specific gene expression; the robust expression of GFP was observed in target HeLa cancer cells, whereas GFP was not visibly expressed in normal PBMCs. The plasmid allowed for the selective visualization of viable HeLa cancer cells in mixed cell cultures containing up to 10000-fold more PBMCs. These findings indicate that the hT/Cm-R-hT expressional system is a valuable tool for detecting viable cancer cells mixed with normal cells. The current system can therefore be applied to the in vitro detection of cancer cells that are disseminated in the blood and other types of body fluid in vivo. Since the current system can also be applied to other types of vectors, including virus vectors, this approach using the hTERT promoter-based construct is expected to become a valuable tool for enhancing cancer specific gene expression.

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  • The assessment of renal cortex and parenchymal volume using automated CT volumetry for predicting renal function after donor nephrectomy 査読

    Yosuke Mitsui, Takuya Sadahira, Motoo Araki, Koichiro Wada, Ryuta Tanimoto, Yuichi Ariyoshi, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Clinical and Experimental Nephrology   22 ( 2 )   1 - 6   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    Background: Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. Methods: Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for &lt
    12 months were excluded leaving 34 patients’ data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor’s postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. Results: Strong correlations were observed preoperatively in a Bland–Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. Conclusion: Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

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  • Expression of tumor suppressor REIC/Dkk-3 by a newly improved adenovirus vector with insertion of a hTERT promoter at the 3'-side of the transgene 査読

    Endy Widya Putranto, Rie Kinoshita, Masami Watanabe, Takuya Sadahira, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Ken Kataoka, Yusuke Inoue, I. Made Winarsa Ruma, I. Wayan Sumardika, Chen Youyi, Miyoko Kubo, Yoshihiko Sakaguchi, Kenji Saito, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh, Masakiyo Sakaguchi

    ONCOLOGY LETTERS   14 ( 1 )   1041 - 1048   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3) overexpression, induced using an adenovirus (Ad)-REIC, has been revealed to have a dramatic therapeutic effect on multiple types of cancer. To achieve an improved therapeutic effect from Ad-REIC on cancer, our group previously developed an enhanced gene expression system, the C-TSC cassette [cytomegalovirus (CMV)-RU5' located upstream (C); another promoter unit composed of triple tandem promoters, human telomerase reverse transcriptase (hTERT), simian virus 40 and CMV, located downstream of the cDNA (TSC); plus a polyadenylation (polyA) signal]. When applied to the conventional Ad-REIC, this novel system induced the development of an enhanced product, Ad-C-TSC-REIC, which exhibited a noticeable anticancer effect. However, there were difficulties in terms of Ad-C-TSC-REIC productivity in HEK293 cells, which are a widely used donor cell line for viral production. Productivity of Ad-C-TSC-REIC was significantly reduced compared with the conventional Ad-REIC, as the Ad-C-TSC-REIC had a significantly higher ability to induce apoptotic cell death of not only various types of cancer cell, but also HEK293 cells. The present study aimed to overcome this problem by modifying the C-TSC structure, resulting in an improved candidate: A C-T cassette (C: CMV-RU5' located upstream; T: another promoter unit composed of a single hTERT promoter, located downstream of the cDNA plus a polyA signal), which demonstrated gene expression comparable to that of the C-TSC system. The improved adenovirus REIC/Dkk-3 product with the C-T cassette, named Ad-C-T-REIC, exhibited a higher expression level of REIC/Dkk3, similar to that of Ad-C-TSC-REIC. Notably, the vector mitigated the cell death of donor HEK293 cells, resulting in a higher rate of production of its adenovirus. These results indicated that Ad-C-T-REIC has the potential to be a useful tool for application in cancer gene therapy.

    DOI: 10.3892/ol.2017.6201

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  • Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies. 査読

    Suzawa K, Shien K, Peng H, Sakaguchi M, Watanabe M, Hashida S, Maki Y, Yamamoto H, Tomida S, Soh J, Asano H, Tsukuda K, Nasu Y, Kumon H, Miyoshi S, Toyooka S

    Anticancer Res   37 ( 1 )   301 - 307   2017年6月

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    記述言語:英語  

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  • Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines 査読

    Yuiko Kato, Kazuhiko Ochiai, Shota Kawakami, Nobuhiro Nakao, Daigo Azakami, Makoto Bonkobara, Masaki Michishita, Masami Morimatsu, Masami Watanabe, Toshinori Omi

    BMC VETERINARY RESEARCH   13 ( 1 )   170   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: The pathological condition of canine prostate cancer resembles that of human androgen-independent prostate cancer. Both canine and human androgen receptor (AR) signalling are inhibited by overexpression of the dimerized co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein a (SGTA), which is considered to cause the development of androgen-independency. Reduced expression in immortalised cells (REIC/Dkk-3) interferes with SGTA dimerization and rescues AR signalling. This study aimed to assess the effects of REIC/Dkk-3 and SGTA interactions on AR signalling in the canine androgen-independent prostate cancer cell line CHP-1.
    Results: Mammalian two-hybrid and Halo-tagged pull-down assays showed that canine REIC/Dkk-3 interacted with SGTA and interfered with SGTA dimerization. Additionally, reporter assays revealed that canine REIC/Dkk-3 restored AR signalling in both human and canine androgen-independent prostate cancer cells. Therefore, we confirmed the interaction between canine SGTA and REIC/Dkk-3, as well as their role in AR signalling.
    Conclusions: Our results suggest that this interaction might contribute to the development of a novel strategy for androgen-independent prostate cancer treatment. Moreover, we established the canine androgen-independent prostate cancer model as a suitable animal model for the study of this type of treatment-refractory human cancer.

    DOI: 10.1186/s12917-017-1094-4

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  • RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice 査読

    Hirofumi Noguchi, Koji Sugimoto, Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi

    SCIENTIFIC REPORTS   7 ( 1 )   3043 - 3043   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice. However, our recent study showed that 11R-VIVIT affected cell viability in vitro when it was used at higher concentration because of the VIVIT sequence. The aim of this study is to develop a safer NFAT inhibitor (RCAN-11R) that does not affect cell viability, and which is less toxic than calcineurin inhibitors. The minimal sequence of the protein family of regulators of calcineurin (RCAN) that is responsible for the inhibition of calcineurin-NFAT signaling was recently characterized. The peptide could selectively interfere with the calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase, similar to 11R-VIVIT. RCAN-11R did not affect cell viability when it was used at a higher concentration than the toxic concentration of 11R-VIVIT. RCAN-11R could therefore be useful as a therapeutic agent that is less toxic than current drugs or 11R-VIVIT.

    DOI: 10.1038/s41598-017-02934-3

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  • The canine prostate cancer cell line CHP-1 shows over-expression of the co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α. 査読

    Azakami D, Nakahira R, Kato Y, Michishita M, Kobayashi M, Onozawa E, Bonkobara M, Kobayashi M, Takahashi K, Watanabe M, Ishioka K, Sako T, Ochiai K, Omi T

    Vet Comp Oncol.   15 ( 2 )   557 - 562   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/vco.12199

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  • Clinical pharmacokinetics of oral levofloxacin and sitafloxacin in epididymal tissue 査読

    Takuya Sadahira, Koichiro Wada, Kazuro Ikawa, Norifumi Morikawa, Hiroaki Kurahashi, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Ayano Ishii, Masami Watanabe, Shinya Uehara, Toyohiko Watanabe, Yasutomo Nasu

    JOURNAL OF INFECTION AND CHEMOTHERAPY   23 ( 4 )   214 - 217   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Objectives: This study aimed to investigate the penetration of fluoroquinolones into human epididymal tissue.
    Methods: The penetration of levofloxacin (LVFX) 500 mg or sitafloxacin (STFX) 100 mg into epididymal tissue was examined. Patients with prostate cancer who were referred for orchiectomy were included. LVFX 500 mg (n = 9) or STFX 100 mg (n = 9) was administered orally 1 h before orchiectomy, and 0.5 g of epididymal tissue and blood samples were collected simultaneously during surgery. Drug concentrations were measured by high-performance liquid chromatography, and patient characteristics and adverse events were analyzed.
    Results: The mean ratio of the epididymal concentration to the serum concentration was 1.48 +/- 0.45 for LVFX and 1.54 +/- 0.81 for STFX. For LVFX, the simulated curves estimated the following: maximum concentrations (Cmax) of 8.84 mu g/ml in serum and 14.1 mu g/g in epididymal tissue and area under the concentration-time curve for 24 h (AUC(24)) of 68.5 mu g h/ml in serum and 108.9 mu g h/g in epididymal tissue. For STFX, the Cmax was 1.22 mu g/ml in serum and 1.66 mu g/g in epididymal tissue, and the AUC24 was 9.58 mu g h/ml in serum and 13.1 mu g h/g in epididymal tissue. Neither treatment-related adverse events nor postoperative urogenital infections were observed.
    Conclusions: The results of this study suggest that oral administration of LVFX 500 mg or STFX 100 mg achieves effective epididymal concentrations for treatment of epididymitis. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jiac.2016.12.010

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  • The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and Its Implication in Human Prostate Cancer Cell Growth Inhibition 査読

    Akihiro Mori, Masami Watanabe, Takuya Sadahira, Yasuyuki Kobayashi, Yuichi Ariyoshi, Hideo Ueki, Koichiro Wada, Kazuhiko Ochiai, Shun-Ai Li, Yasutomo Nasu

    ACTA MEDICA OKAYAMA   71 ( 2 )   135 - 142   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key molecule that promotes cancer progression. We previously developed an adenoviral vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene therapy. The therapeutic effects are based on suppressing the growth of cancer cells, but, the underlying molecular mechanism has not been fully clarified. To elucidate this mechanism, we investigated the effects of Ad-REIC on the expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC also suppressed the cell growth of LNCaP cells. Since other researchers have demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c-Myc protein positively regulate the expression of CD147, we investigated the correlation between the CD147 level and the activation of MAPK and c-Myc expression. Unexpectedly, no positive correlation was observed between CD147 and its possible regulators, suggesting that another signaling pathway was involved in the downregulation of CD147. This is the first study to show the downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the therapeutic effects of Ad-REIC may be due to the downregulation of the cancer-progression factor, CD147.

    DOI: 10.18926/AMO/54982

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  • Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma 査読

    Xiezhao Li, Peng Xu, Chongshan Wang, Naijin Xu, Abai Xu, Yawen Xu, Takuya Sadahira, Motoo Araki, Koichiro Wada, Eiji Matsuura, Masami Watanabe, Junxia Zheng, Pinghua Sun, Peng Huang, Yasutomo Nasu, Chunxiao Liu

    ONCOTARGET   8 ( 13 )   21177 - 21186   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IMPACT JOURNALS LLC  

    Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

    DOI: 10.18632/oncotarget.15505

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  • Programmed death ligand 1 expression in bladder rhabdomyosarcoma and its association with clinicopathological features 査読

    Peng Zhou, Qiongren Wang, Chongshan Wang, Xiezhao Li, Wei Du, Chunxiao Liu, Masami Watanabe, Peng Huang, Abai Xu

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   10 ( 10 )   10565 - 10570   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    The aim of this study was to detect PD-L1 expression in bladder rhabdomyosarcoma and its association with clinicopathological features and patient prognosis. PD-L1 expression was detected in paraffin-embedded sections obtained from 34 patients with bladder rhabdomyosarcoma via immunohistochemistry. Immunohistochemistry results were statistically analyzed to determine their association with patient clinicopathological features and survival outcomes. PD-L1-positive staining was observed in 47.1% (16/34) of patients. Metastatic tumor cells in the lymph nodes of two patients were positive for PD-L1 expression. PD-L1 expression was significantly different with regard to muscularis invasion, but the expression did not affect patient survival outcomes. We confirmed PD-L1 expression in bladder rhabdomyosarcoma, suggesting that PD-1/PD-L1 inhibitors are potential therapeutic agents for patients with bladder rhabdomyosarcoma.

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  • A proteome analysis of pig pancreatic islets and exocrine tissue by liquid chromatography with tandem mass spectrometry 査読

    Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi

    ISLETS   9 ( 6 )   159 - 176   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a proteome analysis method, and the shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolving power. In this study, we analyzed the protein expression in pancreatic tissue by LC-MS/MS. Islets isolated from porcine pancreata (purity 95%) and exocrine tissue (purity 99%) were used in this study. LC-MS/MS showed that 13 proteins were expressed in pancreatic islets only (Group I), 43 proteins were expressed in both islets and exocrine tissue (Group I&E), and 102 proteins were expressed in exocrine tissue only (Group E). Proteins involved in islet differentiation and cell proliferation were identified in Group I (e.g. CLUS, CMGA, MIF). In addition, various functional proteins (e.g. SCG2, TBA1A) were identified in islet by using the new method of principal component analysis (PCA)'. However, the function of such proteins on islets remains unclear. EPCAM was identified in Group E. Group E was found to include proteins involved in clinical inflammatory diseases such as pancreatitis (e.g. CBPA1, CGL, CYTB, ISK1 and PA21B). Many of these identified proteins were reported less frequently in previous studies, and HS71B, NEC2, PRAF3 and SCG1 were newly detected in Group I while CPNS1, DPEP1, GANAB, GDIB, GGT1, HSPB1, ICTL, VILI, MUTA, NDKB, PTGR1, UCHL3, VAPB and VINC were newly detected in Group E. These results show that comprehensive expression analysis of proteins by LC-MS/MS is useful as a method to investigate new factors constructing cellular component, biological process, and molecular function.

    DOI: 10.1080/19382014.2017.1389826

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  • Efficacy and safety of 3 day versus 7 day cefditoren pivoxil regimens for acute uncomplicated cystitis: Multicentre, randomized, open-label trial 査読

    Takuya Sadahira, Okayama Urological Research Group (OURG), Koichiro Wada, Motoo Araki, Ayano Ishii, Atsushi Takamoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon, Teruaki Akaeda, Nobuyuki Akazawa, Naoki Akebi, Daiji Araki, Tohru Araki, Ryoji Arata, Yuichi Ariyoshi, Eiichi Ando, Nobuyoshi Ando, Kazushi Ishii, Tsutomu Ishikawa, Noritaka Ishito, Takaharu Ichikawa, Takaaki Inoue, Miyabi Inoue, Yosuke Inoue, Shin Irie, Takehiro Iwata, Tatsuya Uesugi, Shinya Uehara, Katsutoshi Uematsu, Satoshi Uno, Kohei Edamura, Shin Ebara, Yuko Oiwa, Tadashi Oeda, Teruhisa Ohashi, Yozo Ohashi, Hideo Ozawa, Junzo Ochi, Noriaki Ono, Seiji Kai, Haruki Kaku, Satoshi Katayama, Yasuhiro Katayama, Tetuzo Kaneshige, Keiichiro Kawauchi, Masashi Kawaguchi, Tatsushi Kawada, Taiki Kanbara, Mikio Kishi, Ryo Kishimoto, Nobuyuki Kusaka, Norihiro Kusumi, Kimito Kunitomi, Risa Kubota, Hiroaki Kurahashi, Hironori Kojima, Tomoko Kobayashi, Makoto Kobuke, Katsuyoshi Kondo, Takashi Saika, Kazuma Sakaeda, Koji Sakuramoto, Shinichi Sako, Tomoko Sako, Taketo Sasaoka, Katsumi Sasaki, Yoshimasa Jo, Morito Sugimoto, Yuko Seno, Akira Takao, Kosuke Takamura, Kousuke Takamura, Hitoshi Takamoto, Katsuji Takeda, Tadasu Takenaka, Daisuke Tanaka, Ryuta Tanimoto, Masaya Tsugawa, Tomoyasu Tsushima, Hiromu Tsuboi, Syunji Tojo, Kenji Tokinaga, Yusuke Tominaga, Keisuke Doi, Atsushi Nagai, Hirochika Nakajima, Tetsuya Nakada, Hirokazu Nakatsuka, Aya Nakamura, Yasuki Nakayama, Yoshitsugu Nasu, Daisuke Nishikawa, Jun Nishiguchi, Yoshio Nishitani, Shingo Nishimura, Motoichi Nishimura, Yasuhiro Nishiyama, Hajime Nibuno, Kunihiro Nozaki, Hiroyuki Nose, Gaku Noda, Hideaki Hashimoto, Kazuhiro Hata, Toshihide Hayashi, Nobuki Hayashi, Syunji Hayata, Ryoei Hara, Takeshi Hirata, Tomohiro Fujii, Kei Fujio, Ryuji Fujita, Kensuke Bekku, Takanori Maehara, Yoshio Maki, Yuko Matsumoto, Daisuke Manabe, Yusuke Mayumi, Yuki Maruyama, Yosuke Mitsui, Sadayuki Miyaji, Syuhei Munemasa, Wataru Murao, Takanori Murakami, Tadashi Murata, Akihiro Mori, Akira Morita, Koichi Monden, Tomoya Yamasaki, Masahiro Yamashita, Daiduke Yamada, Toyoko Yamato, Toru Yamane, Tomoaki Yamanoi, Yasuo Yamamoto, Kazuaki Yukari, Teruhiko Yokoyama, Takashi Yoshioka, Yuichi Watanabe

    Journal of Antimicrobial Chemotherapy   72 ( 2 )   529 - 534   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press  

    Background: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, β-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria. Objectives: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment. Methods: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study. Results: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n=51) or 7 day (n=53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 5-9 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P=1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P=0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial. Conclusions: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

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  • Dynamin2 GTPase contributes to invadopodia formation in invasive bladder cancer cells 査読

    Yubai Zhang, Maya Nolan, Hiroshi Yamada, Masami Watanabe, Yasutomo Nasu, Kohji Takei, Tetsuya Takeda

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   480 ( 3 )   409 - 414   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Cancer cell invasion is mediated by actin-based membrane protrusions termed invadopodia. Invadopodia consist of "core" F-actin bundles associated with adhesive and proteolytic machineries promoting cell invasion by degrading extracellular matrix (ECM). Formation of the F-actin core in invadopodia is regulated by various actin-binding proteins including Arp2/3 complex and cortactin. Dynamin GTPase localizes to the invadopodia and is implicated in cancer cell invasion, but its precise role at the invadopodia remained elusive.
    In this study, we examined the roles of dynamin at the invadopodia of bladder cancer cells. Although all three dynamin isoforms (dynamin1, 2 and 3) are expressed in human bladder cancer cell line T24, only dynamin2 localizes to the invadopodia. Inhibition of dynamin2 function, using either RNA interference (RNAi) or the dynamin specific inhibitor Dynasore, caused defects in invadopodia formation and suppressed invasive activity of 124 bladder cancer cells. Structure-function analysis using dynamin2 deletion fragments identified the proline/arginine-rich domain (PRD) of dynamin2 as indispensable for invadopodia formation and invasiveness of 124 cells. Thus, dynamin2 contributes to bladder cancer invasion by controlling invadopodia formation in bladder cancer cells and may prove a valuable therapeutic target. (C) 2016 Elsevier Inc. All rights reserved.

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  • Adenovirus vector carrying REICIDKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy 査読

    H. Kumon, Y. Ariyoshi, K. Sasaki, T. Sadahira, M. Araki, S. Ebara, H. Yanai, M. Watanabe, Y. Nasu

    CANCER GENE THERAPY   23 ( 11 )   400 - 409   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kaftan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11) and 1.0 x 10(12) viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 x 10(12) vp in 3.6 ml (n=6) Was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration With cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+2:

    DOI: 10.1038/cgt.2016.53

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  • Comparison of Purification Solutions With Different Osmolality for Porcine Islet Purification. 査読

    Miyagi-Shiohira C, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M, Noguchi H

    Cell Med   9 ( 1月2日 )   53 - 59   2016年9月

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    記述言語:英語  

    DOI: 10.3727/215517916X693140

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  • The Evaluation of Islet Purification Methods That Use Large Bottles to Create a Continuous Density Gradient. 査読

    Miyagi-Shiohira C, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M, Noguchi H

    Cell Med   9 ( 1月2日 )   45 - 51   2016年9月

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    記述言語:英語  

    DOI: 10.3727/215517916X693131

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  • Evaluation of Serum-Free, Xeno-Free Cryopreservation Solutions for Human Adipose-Derived Mesenchymal Stem Cells. 査読

    Miyagi-Shiohira C, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M, Noguchi H

    Cell Med   9 ( 1月2日 )   15 - 20   2016年9月

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    記述言語:英語  

    DOI: 10.3727/215517916X693122

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  • A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy 査読

    Tetsuo Oka, Kazuhiko Kurozumi, Yosuke Shimazu, Tomotsugu Ichikawa, Joji Ishida, Yoshihiro Otani, Toshihiko Shimizu, Yusuke Tomita, Masakiyo Sakaguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Isao Date

    SCIENTIFIC REPORTS   6   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and therapeutic gene in many human cancers. Recently, an adenovirus REIC vector with the super gene expression system (Ad-SGE-REIC) was developed to increase REIC/Dkk-3 expression and enhance therapeutic effects compared with the conventional adenoviral vector (Ad-CAG-REIC). In this study, we investigated the in vitro and in vivo effects of Ad-SGE-REIC on malignant glioma. In U87 Delta EGFR and GL261 glioma cells, western blotting confirmed that robust upregulation of REIC/Dkk-3 expression occurred in Ad-SGE-REIC-transduced cells, most notably after transduction at a multiplicity of infection of 10. Cytotoxicity assays showed that Ad-SGE-REIC resulted in a time-dependent and significant reduction in the number of malignant glioma cells attaching to the bottom of culture wells. Xenograft and syngeneic mouse intracranial glioma models treated with Ad-SGE-REIC had significantly longer survival than those treated with the control vector Ad-LacZ or with Ad-CAG-REIC. This study demonstrated the anti-glioma effect of Ad-SGE-REIC, which may represent a promising strategy for the treatment of malignant glioma.

    DOI: 10.1038/srep33319

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  • MCAM, as a novel receptor for S100A8/A9, mediates progression of malignant melanoma through prominent activation of NF-κB and ROS formation upon ligand binding. 査読

    Ruma IM, Putranto EW, Kondo E, Murata H, Watanabe M, Huang P, Kinoshita R, Futami J, Inoue Y, Yamauchi A, Sumardika IW, Youyi C, Yamamoto K, Nasu Y, Nishibori M, Hibino T, Sakaguchi M

    Clin Exp Metastasis.   33 ( 6 )   609 - 627   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10585-016-9801-2

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  • The Efficacy of Rituximab in High-risk Renal Transplant Recipients 査読

    Motoo Araki, Koichiro Wada, Yosuke Mitsui, Risa Kubota, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

    ACTA MEDICA OKAYAMA   70 ( 4 )   295 - 297   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti-CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients.

    DOI: 10.18926/AMO/54507

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  • Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer 査読

    H. Sawahara, H. Shiraha, D. Uchida, H. Kato, T. Nagahara, M. Iwamuro, J. Kataoka, S. Horiguchi, M. Watanabe, M. Sakaguchi, A. Takaki, K. Nouso, Y. Nasu, H. Kumon, H. Okada

    CANCER GENE THERAPY   23 ( 8 )   278 - 283   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pantreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied, Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.

    DOI: 10.1038/cgt.2016.31

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  • A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis 査読

    Koichiro Wada, Shinya Uehara, Ayano Ishii, Takuya Sadahira, Masumi Yamamoto, Ritsuko Mitsuhata, Atsushi Takamoto, Motoo Araki, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

    ACTA MEDICA OKAYAMA   70 ( 4 )   299 - 302   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants.

    DOI: 10.18926/AMO/54508

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  • Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells 査読

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Hiroaki Sawahara, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   31 ( 6 )   1154 - 1159   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and AimReduced expression in immortalized cells/dickkopf-3 (REIC/DKK3) is a reported tumor suppressor gene and has potential to become an innovative therapy for various cancers. We examined the antitumor immunological effects of human REIC/DKK3 protein against pancreatic cancer.
    MethodsActivation of extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 by REIC/DKK3 protein was assessed in human peripheral blood mononuclear cells using immunoblotting. Pancreatic cancer cell lines (AsPC-1 and MIA Paca-2) were cocultured with peripheral blood mononuclear cells, and the anticancer effects of REIC/DKK3 protein were assessed using the methyl thiazole tetrazolium, cytotoxicity, and enzyme-linked immunospot assays. The antitumor immunological effects of the combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells were also assessed in a pancreatic cancer model using non-obese diabetic/severe combined immunodeficiency mice.
    ResultsThe REIC/DKK3 protein activated extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 in peripheral blood mononuclear cells. REIC/DKK3 protein inhibited in vitro cancer cell viability and enhanced cytotoxicity when incubated with peripheral blood mononuclear cells. REIC/DKK3 protein induced significant production of interferon gamma from lymphocytes incubated with pancreatic cancer cells, indicating that CD8+ T cells were activated in the peripheral blood mononuclear cells when cocultured with AsPC-1 and MIA Paca-2 in the presence of REIC/DKK3 protein. Combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells produced in vivo anticancer immunostimulatory effects on pancreatic cancer cells.
    ConclusionsThe REIC/DKK3 protein and peripheral blood mononuclear cells synergistically enhanced anticancer immunological effects against pancreatic cancer cells. The observed immunomodulatory effect of combined treatment likely occurs in adenovirus-mediated REIC/DKK3 gene therapy and provides important clues to the therapeutic mechanisms involving immune cells.

    DOI: 10.1111/jgh.13259

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  • The induction of antigen-specific CTL by in situ Ad-REIC gene therapy 査読

    Y. Ariyoshi, M. Watanabe, S. Eikawa, C. Yamazaki, T. Sadahira, T. Hirata, M. Araki, S. Ebara, Y. Nasu, H. Udono, H. Kumon

    GENE THERAPY   23 ( 5 )   408 - 414   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

    DOI: 10.1038/gt.2016.7

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  • [Gene therapy]. 査読

    Watanabe M, Sadahira T, Nasu Y

    Nihon rinsho. Japanese journal of clinical medicine   74 Suppl 3   221 - 225   2016年5月

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  • Promising Therapeutic Efficacy of a Novel REIC/Dkk-3 Expressing Adenoviral Vector for Hepatocellular Carcinoma 査読

    Hiroaki Sawahara, Shiraha Hidenori, Uchida Daisuke, Sakaguchi Masakiyo, Watanabe Masami, Nasu Yasutomo, Kumon Hiromi, Okada Hiroyuki

    GASTROENTEROLOGY   150 ( 4 )   S1153   2016年4月

  • Development of a Novel REIC/DKK-3-Encoding Adenoviral Agent: Its Robust and Promising Therapeutic Effects in Pancreatic Cancer 査読

    Uchida Daisuke, Shiraha Hidenori, Kato Hironari, Hiroaki Sawahara, Sakaguchi Masakiyo, Watanabe Masami, Nasu Yasutomo, Kumon Hiromi, Okada Hiroyuki

    GASTROENTEROLOGY   150 ( 4 )   S294   2016年4月

  • Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity 査読

    Kazuhiko Ochiai, Masami Morimatsu, Yuiko Kato, Toshina Ishiguro-Oonuma, Chihiro Udagawa, Oumaporn Rungsuriyawiboon, Daigo Azakami, Masaki Michishita, Yuichi Ariyoshi, Hideo Ueki, Yasutomo Nasu, Hiromi Kumon, Masami Watanabe, Toshinori Omi

    ONCOTARGET   7 ( 3 )   3273 - 3286   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IMPACT JOURNALS LLC  

    REIC/DKK-3 is a tumor suppressor, however, its intracellular physiological functions and interacting molecules have not been fully clarified. Using yeast two-hybrid screening, we found that small glutamine-rich tetratricopeptide repeat-containing protein a (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, is a novel interacting partner of REIC/DKK-3. Mammalian two-hybrid and pull-down assay results indicated that the SGTA-REIC/DKK-3 interaction involved the N-terminal regions of both REIC/DKK-3 and SGTA and that REIC/DKK-3 interfered with the dimerization of SGTA, which is a component of the AR complex and a suppressor of dynein motor-dependent AR transport and signaling. A reporter assay in human prostate cancer cells that displayed suppressed AR signaling by SGTA showed recovery of AR signaling by REIC/DKK-3 expression. Considering these results and our previous data that REIC/DKK-3 interacts with the dynein light chain TCTEX-1, we propose that the REIC/DKK-3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling.

    DOI: 10.18632/oncotarget.6488

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  • Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy 査読

    Hiromi Kumon, Katsumi Sasaki, Yuichi Ariyoshi, Takuya Sadahira, Motoo Araki, Shin Ebara, Hiroyuki Yanai, Masami Watanabe, Yasutomo Nasu

    CTS-CLINICAL AND TRANSLATIONAL SCIENCE   8 ( 6 )   837 - 840   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11), and 1.0 x 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 x 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199)

    DOI: 10.1111/cts.12362

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  • Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer. 査読

    Kato Y, Ochiai K, Michishita M, Azakami D, Nakahira R, Morimatsu M, Ishiguro-Oonuma T, Yoshikawa Y, Kobayashi M, Bonkobara M, Kobayashi M, Takahashi K, Watanabe M, Omi T

    Vet J   206 ( 2 )   143 - 148   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.tvjl.2015.08.002

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  • REIC/Dkk-3遺伝子治療の胸部悪性腫瘍に対する免疫刺激を介する抗腫瘍効果

    諏澤 憲, 枝園 和彦, 阪口 政清, 渡部 昌実, 橋田 真輔, 宗 淳一, 山本 寛斉, 牧 祐歩, 佃 和憲, 那須 保友, 公文 裕巳, 三好 新一郎, 豊岡 伸一

    日本癌学会総会記事   74回   J - 1224   2015年10月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • A novel in situ permeation system and its utility in cancer tissue ablation 査読

    Masami Watanabe

    INTERNATIONAL JOURNAL OF ONCOLOGY   47 ( 3 )   875 - 883   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Focal ablation therapy is an emerging treatment modality for localized cancer lesions. It is an attractive strategy for inhibiting tumor progression and preventing morbidity associated with open surgery. As for intratissue drug delivery systems for use in local therapy, the convection-enhanced delivery (CED) of liquid drugs has been utilized, particularly for the treatment of malignant brain tumors. Although the conventional CED system is useful for providing drug/vehicle-based local therapy, there are several reported disadvantages in terms of the ability to control the extent of drug diffusion. We herein developed and validated a novel in situ permeation (ISP)-MW-1 system for achieving intratissue drug diffusion. The ISP system includes a perfusion catheter connected to an injector and aspirator, which enables intratissue perfusion of the solute diluted in the vehicle in the tip-inserted cavity. We subsequently evaluated the utility of the ISP-MW-1 system for in situ permeation in a subcutaneous tumor model in hamsters. Dehydrated ethanol, saline and 50% acetic acid were evaluated as the vehicle, and methylene blue was used as a dissolved substance for evaluating the diffusion of the agent. As a result, almost all of the tumor tissue within the capsule (tumor size: 3 cm) was permeated with the dehydrated ethanol and 50% acetic acid and partially with the saline. We further demonstrated that ISP treatment with 50% acetic acid completely ablated the subcutaneous tumors in all of the treated hamsters (n=3). Therefore, the ISP-MW-1 system is a promising approach for controlling the intratissue diffusion of therapeutic agents and for providing local ablation therapy for cancer lesions. We believe that this system may be applicable to a broad range of medicinal and industrial fields, such as regenerative medicine, drug delivery systems, biochemistry and material technologies as well as cancer therapy.

    DOI: 10.3892/ijo.2015.3068

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  • Distant Bystander Effect of REIC/Dkk-3 Gene Therapy through Immune System Stimulation in a Murine Model of Thoracic Malignancies 査読

    Suzawa Ken, Shien Kazuhiko, Huang Peng, Sakaguchi Masakiyo, Watanabe Masami, Hashida Shinsuke, Soh Junichi, Yamamoto Hiromasa, Maki Yuho, Asano Hiroaki, Tsukuda Kazunori, Nasu Yasutomo, Kumon Hiromi, Miyoshi Shinichiro, Toyooka Shinichi

    JOURNAL OF THORACIC ONCOLOGY   10 ( 9 )   S599   2015年9月

  • Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone. 査読

    Yamada H, Kikuchi T, Masumoto T, Wei FY, Abe T, Takeda T, Nishiki T, Tomizawa K, Watanabe M, Matsui H, Takei K

    Biol Cell   107 ( 9 )   319 - 330   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/boc.201500032

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  • Islet Culture/Preservation Before Islet Transplantation. 査読

    Noguchi H, Miyagi-Shiohira C, Kurima K, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M

    Cell Med.   8 ( 1月2日 )   25 - 29   2015年8月

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  • Cryopreservation of Adipose-Derived Mesenchymal Stem Cells. 査読

    Miyagi-Shiohira C, Kurima K, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M, Noguchi H

    Cell Med.   8 ( 1月2日 )   3 - 7   2015年8月

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    記述言語:英語  

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  • The cysteine-rich core domain of REIC/Dkk-3 is critical for its effect on monocyte differentiation and tumor regression 査読

    Rie Kinoshita, Masami Watanabe, Peng Huang, Shun-Ai Li, Masakiyo Sakaguchi, Hiromi Kumon, Junichiro Futami

    ONCOLOGY REPORTS   33 ( 6 )   2908 - 2914   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor-suppressor gene and has been studied as a promising therapeutic gene for cancer gene therapy. Intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) elicits cancer cell-specific apoptosis and anticancer immune responses. The cytokine-like effect of secretory REIC/Dkk-3 on the induction of dendritic cell (DC)-like cell differentiation from monocytes plays a role in systemic anticancer immunity. In the present study, we generated recombinant full-length and N-terminally truncated REIC/Dkk-3 to characterize the biological activity of the protein. During the purification procedure, we identified a 17 kDa cysteine-rich stable product (C17-REIC) showing limited degradation. Further analysis showed that the C17-REIC domain was sufficient for the induction of DC-like cell differentiation from monocytes. Concomitant with the differentiation of DCs, the REIC/Dkk-3 protein induced the phosphorylation of glycogen synthase kinase 3 beta (GSK-3 beta) and signal transducers and activators of transcription (STAT) at a level comparable to that of granulocyte/macrophage colony-stimulating factor. In a mouse model of subcutaneous renal adenocarcinoma, intraperitoneal injection of full-length and C17-REIC proteins exerted anticancer effects in parallel with the activation of immunocompetent cells such as DCs and cytotoxic T lymphocytes in peripheral blood. Taken together, our results indicate that the stable cysteine-rich core region of REIC/Dkk-3 is responsible for the induction of anticancer immune responses. Because REIC/Dkk-3 is a naturally circulating serum protein, the upregulation REIC/Dkk-3 protein expression could be a promising option for cancer therapy.

    DOI: 10.3892/or.2015.3885

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  • Potential Factors for the Differentiation of ESCs/iPSCs Into Insulin-Producing Cells. 査読

    Takako Tsugata, Naruo Nikoh, Tatsuya Kin, Issei Saitoh, Yasufumi Noguchi, Hideo Ueki, Masami Watanabe, Andrew M, James Shapiro, Hirofumi Noguchi

    Cell Medicine   7 ( 2 )   83 - 93   2015年4月

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    記述言語:英語  

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  • Polymorphisms of canine BRCA2 BRC repeats affecting interaction with RAD51 査読

    Kazuhiko Ochiai, Toshina Ishiguro-Oonuma, Yasunaga Yoshikawa, Chihiro Udagawa, Yuiko Kato, Masami Watanabe, Makoto Bonkobara, Masami Morimatsu, Toshinori Omi

    BIOMEDICAL RESEARCH-TOKYO   36 ( 2 )   155 - 158   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    Mutations in the breast cancer susceptibility gene BRCA2 leading to the failure of interactions with the recombinase RAD51 are associated with an increased risk of cancer in humans. This interaction depends on the eight BRC repeat (BRC1-8) sequences in BRCA2. We previously reported that canine BRC3 has two polymorphisms (T1425P and K1435R) influencing the interaction with RAD51, and 1435R was identified in mammary tumor dog samples. In this study, we investigated the sequence variations of BRC3 and 4 in 236 dogs of five breeds. Allele frequencies of 1425P and 1435R were 0.063 and 0.314, respectively, and there was no other polymorphism in the sequenced region. A mammalian two-hybrid assay using BRC3-4 sequences demonstrated that 1425P allele reduced the binding strength with RAD51 but 1435R had no effect. These results may provide an insight into the functions of not only individual but also multiple BRC repeats of BRCA2 in dogs.

    DOI: 10.2220/biomedres.36.155

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  • A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment 査読

    Kei Fujio, Masami Watanabe, Hideo Ueki, Shun-Ai Li, Rie Kinoshita, Kazuhiko Ochiai, Junichiro Futami, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

    ONCOLOGY REPORTS   33 ( 4 )   1585 - 1592   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic antigen-vaccination strategy to enhance the therapeutic effects.

    DOI: 10.3892/or.2015.3770

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  • Ad-REIC gene therapy: Promising results in a patient with metastatic CRPC following chemotherapy 査読

    Hiromi Kumon, Katsumi Sasaki, Yuichi Ariyoshi, Takuya Sadahira, Shin Ebara, Takao Hiraki, Susumu Kanazawa, Hiroyuki Yanai, Masami Watanabe, Yasutomo Nasu

    Clinical Medicine Insights: Oncology   9   31 - 38   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Libertas Academica Ltd.  

    A 63-year-old man with metastatic castration-resistant prostate cancer (CRPC) was successfully treated for two years with in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk‑3 gene (Ad-REIC), following chemotherapy. Ad-REIC mediates simultaneous induc-tion of cancer-selective apoptosis and augmentation of antitumor immunity, and a Phase I/IIa clinical study on Ad-REIC has been conducted at Okayama University Hospital since January 2011. At the time of enrollment in December 2012, the patient presented with rapid progression of lymph node (LN) metastases. Two scheduled Ad-REIC injections and 10 additional Ad-REIC injections into metastatic pelvic and para-aortic LNs under CT guidance, with an average four weeks’ interval, exhibited the potent direct and indirect effects of Ad-REIC as a therapeutic cancer vaccine. During the next 12 months, three additional injections into para-aortic LNs showing regrowth achieved adequate control of all metastatic LNs with prostate-specific antigen (PSA) decline, without any particular adverse events.

    DOI: 10.4137/CMO.S23252

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  • Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma 査読

    Y. Shimazu, K. Kurozumi, T. Ichikawa, K. Fujii, M. Onishi, J. Ishida, T. Oka, M. Watanabe, Y. Nasu, H. Kumon, I. Date

    GENE THERAPY   22 ( 2 )   146 - 154   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified as a gene whose expression is reduced in many human cancers. REIC/Dkk-3 expression is also downregulated in malignant glioma and regulates cell growth through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of integrins, has demonstrated preclinical efficacy against malignant glioma. In this study, we investigated the antiglioma effect of combination therapy using an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in malignant glioma cell lines was also confirmed with western blot analysis. After treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells was significantly reduced in a time-dependent manner. In vivo, there was a statistically significant increase in the survival of mice treated with Ad-REIC and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the antiglioma efficacy of Ad-REIC. These results may lead to a promising new approach for the treatment of malignant glioma.

    DOI: 10.1038/gt.2014.100

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  • Induction of tissue-specific stem cells by reprogramming factors, and tissue-specific selection 査読

    H. Noguchi, I. Saitoh, T. Tsugata, H. Kataoka, M. Watanabe, Y. Noguchi

    CELL DEATH AND DIFFERENTIATION   22 ( 1 )   145 - 155   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Although induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells, there are still several unresolved issues related to the use of iPS cells for clinical applications, such as teratoma formation. In this study, we were able to generate tissue-specific stem (induced tissue-specific stem; iTS) cells from the pancreas (iTS-P) or liver (iTS-L) by transient overexpression of reprogramming factors, combined with tissue-specific selection. The generation of iTS cells was easier than that of iPS cells. The iTS-P/iTS-L cells express genetic markers of endoderm and pancreatic/hepatic progenitors and were able to differentiate into insulin-producing cells/hepatocytes more efficiently than ES cells. Subcutaneous transplantation of both types of iTS cells into immunodeficient mice resulted in no teratoma formation. The technology used for the transient overexpression of reprogramming factors and tissue-specific selection may be useful for the generation of other tissue-specific stem cells, and the generation of iTS cells could have important implications for the clinical application of stem cells.

    DOI: 10.1038/cdd.2014.132

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  • Potential Factors for the Differentiation of ESCs/iPSCs Into Insulin-Producing Cells. 査読

    Tsugata T, Nikoh N, Kin T, Saitoh I, Noguchi Y, Ueki H, Watanabe M, James Shapiro AM, Noguchi H

    Cell Med   7 ( 2 )   83 - 93   2014年12月

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    記述言語:英語  

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  • Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer 査読

    Chao Ma, Chunxiao Liu, Peng Huang, Haruki Kaku, Jie Chen, Kai Guo, Hideo Ueki, Akiko Sakai, Yasutomo Nasu, Hiromi Kumon, Kenji Shimizu, Masami Watanabe

    ONCOLOGY LETTERS   8 ( 2 )   789 - 794   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The Wnt signaling pathway plays a crucial role in human cancer development, and axis inhibition protein 2 (Axin2) is a master scaffold protein involved in Wnt signaling. Axin2 negatively regulates Wnt signaling and acts as a tumor suppressor protein. The present study evaluated the association between the Axin2 single nucleotide polymorphism (SNP) rs2240308 [guanine (G)/adenine (A)] and the incidence of prostate cancer. In total, 103 patients with prostate cancer and 100 cancer-free control males were included in this case-control study, and were genotyped using the genomic DNA extracted from peripheral blood samples. The results revealed a higher incidence of prostate cancer in the subjects with the homozygous GG genotype and a reduced cancer incidence in the patients with the GA genotype of the rs2240308 SNP (G/A) in the Axin2 gene. T-he adjusted odds ratio for carriers with the GA genotype was 0.377 (95% CI, 0.206-0.688; P=0.001) and that for the AA genotype was 0.830 (95% CI, 0.309-2.232; P=0.712) compared with the GG genotype. Therefore, the GA genotype was found to exhibit a protective effect that decreased the risk of prostate cancer. To the best of our knowledge, this is the first study to demonstrate the significant association between this SNP (rs2240308, G/A) and the risk of prostate cancer. This association indicates the possibility that the variations in the Axin2 gene in this position may play a significant role in promoting the development of cancer in the prostate. We believe that the Axin2 SNP (rs2240308) could be a useful biomarker for the predisposition and early diagnosis of the disease.

    DOI: 10.3892/ol.2014.2177

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  • Dramatic Increase in Expression of a Transgene by Insertion of Promoters Downstream of the Cargo Gene 査読

    Masakiyo Sakaguchi, Masami Watanabe, Rie Kinoshita, Haruki Kaku, Hideo Ueki, Junichiro Futami, Hitoshi Murata, Yusuke Inoue, Shun-Ai Li, Peng Huang, Endy Widya Putranto, I. Made Winarsa Ruma, Yasutomo Nasu, Hiromi Kumon, Nam-ho Huh

    MOLECULAR BIOTECHNOLOGY   56 ( 7 )   621 - 630   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    For expression of genes in mammalian cells, various vectors have been developed using promoters including CMV, EF-1 alpha, and CAG promoters and have been widely used. However, such expression vectors sometimes fail to attain sufficient expression levels depending on the nature of cargo genes and/or on host cell types. In the present study, we aimed to develop a potent promoter system that enables high expression levels of cargo genes ubiquitously in many different cell types. We found that insertion of an additional promoter downstream of a cargo gene greatly enhanced the expression levels. Among the constructs we tested, C-TSC cassette (C: CMV-RU5' located upstream; TSC: another promoter unit composed of triple tandem promoters, hTERT, SV40, and CMV, located downstream of the cDNA plus a polyadenylation signal) had the most potent capability, showing far higher efficiency than that of potent conventional vector systems. The results indicate that the new expression system is useful for production of recombinant proteins in mammalian cells and for application as a gene therapeutic measure.

    DOI: 10.1007/s12033-014-9738-0

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  • Immunological aspects of REIC/Dkk-3 gene therapy : the mechanism of the robust anti-tumor effects. 査読

    Masami Watanabe, Peng Huang, Fernando Abarzua, Haruki Kaku, Katsumi Sasaki, Hideo Ueki, Toyohiko Wananabe, Yasutomo Nasu, Hiromi Kumon

    JOURNAL OF GENE MEDICINE   16 ( 7-8 )   226 - 227   2014年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • Establishment of a pancreatic stem cell line from fibroblast-derived induced pluripotent stem cells 査読

    Takashi Kuise, Hirofumi Noguchi, Hiroshi Tazawa, Takashi Kawai, Masaya Iwamuro, Issei Saitoh, Hitomi Usui Kataoka, Masami Watanabe, Yasufumi Noguchi, Toshiyoshi Fujiwara

    BIOMEDICAL ENGINEERING ONLINE   13   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: For cell therapies to treat diabetes, it is important to produce a sufficient number of pancreatic endocrine cells that function similarly to primary islets. Induced pluripotent stem (iPS) cells represent a potentially unlimited source of functional pancreatic endocrine cells. However, the use of iPS cells for laboratory studies and cell-based therapies is hampered by their high tumorigenic potential and limited ability to generate pure populations of differentiated cell types in vitro. The purpose of this study was to establish a pancreatic stem cell line from iPS cells derived from mouse fibroblasts.
    Methods: Mouse iPS cells were induced to differentiate into insulin-producing cells by a multi-step differentiation protocol, which was conducted as described previously with minor modifications. Selection of the pancreatic stem cell was based on morphology and Pdx1 expression. The pancreatic potential of the pancreatic stem cells was evaluated using a reverse transcription PCR, real-time PCR, immunofluorescence, and a glucose challenge test. To assess potential tumorigenicity of the pancreatic stem cells, the cells were injected into the quadriceps femoris muscle of the left hindlimb of nude mice.
    Results: The iPS-derived pancreatic stem cells expressed the transcription factor -Pdx1- a marker of pancreatic development, and continued to divide actively beyond passage 80. Endocrine cells derived from these pancreatic stem cells expressed insulin and pancreatic genes, and they released insulin in response to glucose stimulation. Mice injected with the pancreatic stem cells did not develop tumors, in contrast to mice injected with an equal number of iPS cells.
    Conclusion: This strategy provides a new approach for generation of insulin-producing cells that is more efficient and safer than using iPS cells. We believe that this approach will help to develop a patient-specific cell transplantation therapy for diabetes in the near future.

    DOI: 10.1186/1475-925X-13-64

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  • Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer 査読

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Takahito Yagi, Hiromi Kumon, Kazuhide Yamamoto

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   29 ( 5 )   973 - 983   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer.
    MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine.
    ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.
    ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

    DOI: 10.1111/jgh.12501

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  • A novel gene expression system strongly enhances the anticancer effects of a REIC/Dkk-3-encoding adenoviral vector 査読

    Masami Watanabe, Masakiyo Sakaguchi, Rie Kinoshita, Haruki Kaku, Yuichi Ariyoshi, Hideo Ueki, Ryuta Tanimoto, Shin Ebara, Kazuhiko Ochiai, Junichiro Futami, Shun-Ai Li, Peng Huang, Yasutomo Nasu, Nam-Ho Huh, Hiromi Kumon

    ONCOLOGY REPORTS   31 ( 3 )   1089 - 1095   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Gene expression systems with various promoters, including the cytomegalovirus (CMV) promoter, have been developed to increase the gene expression in a variety of normal and cancer cells. In particular, in the clinical trials of cancer gene therapy, a more efficient and robust gene expression system is required to achieve sufficient therapeutic outcomes. By inserting the triple translational enhancer sequences of human telomerase reverse transcriptase (hTERT), Simian virus 40 (SV40) and CMV downstream of the sequence of the BGH polyA, we were able to develop a novel gene expression system that significantly enhances the expression of the genes of interest. We termed this novel gene expression cassette the super gene expression (SGE) system, and herein verify the utility of the SGE cassette for a replication-deficient adenoviral vector. We newly developed an adenoviral vector expressing the tumor suppressor, reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), based on the CMV promoter-driven SGE system (Ad-SGE-REIC) and compared the therapeutic utility of Ad-SGE-REIC with that of the conventional adenoviral vectors (Ad-CMV-REIC or Ad-CAG-REIC). The results demonstrated that the CMV promoter-SGE system allows for more potent gene expression, and that the Ad-SGE-REIC is superior to conventional adenoviral systems in terms of the REIC protein expression and therapeutic effects. Since the SGE cassette can be applied for the expression of various therapeutic genes using various vector systems, we believe that this novel system will become an innovative tool in the field of gene expression and gene therapy.

    DOI: 10.3892/or.2013.2958

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  • Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review) 査読

    Masami Watanabe, Yasutomo Nasu, Hiromi Kumon

    ONCOLOGY LETTERS   7 ( 3 )   595 - 601   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor suppressor and therapeutic gene and has been studied with respect to the application of cancer gene therapy. Our previous studies demonstrated that the intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) suppresses tumor growth in mouse models of prostate, breast and testicular cancer and malignant mesothelioma. The mechanisms underlying these antitumor therapeutic effects have only been clarified recently. It has been demonstrated that Ad-REIC treatment inhibits cancer progression via the upregulation of systemic anticancer immunity. Under experimental conditions, autologous cancer vaccination via cancer-specific apoptosis and anticancer immune activation is a possible therapeutic mechanism. The robust anticancer effects observed in previous preclinical studies support the clinical utility of Ad-REIC. At present, a phase I-IIa study of Ad-REIC gene therapy in prostate cancer patients is ongoing. The current study reviews the observations of previous fundamental studies and summarizes the anticancer mechanisms of intratumoral Ad-REIC treatment in terms of cancer vaccination.

    DOI: 10.3892/ol.2013.1777

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  • Anti-Cancer Effects of REIC/Dkk-3-encoding Adenoviral Vector for the Treatment of Non-small Cell Lung Cancer 査読

    Kazuhiko Shien, Norimitsu Tanaka, Masami Watanabe, Junichi Soh, Masakiyo Sakaguchi, Keitaro Matsuo, Hiromasa Yamamoto, Masashi Furukawa, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Nam-Ho Huh, Shinichiro Miyoshi, Hiromi Kumon, Shinichi Toyooka

    PLOS ONE   9 ( 2 )   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Objectives: REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC).
    Materials and Methods: We examined the anti-tumor effect of Ad-REIC on 25 NSCLC cell lines in vitro and A549 cells in vivo. Two of these cell lines were artificially established as EGFR-tyrosine kinase inhibitor (TKI) resistant sublines.
    Results: Ad-REIC-treatment inhibited the cell viability by 40% or more in 13 (52%) of the 25 cell lines at multiplicity of infection (MOI) of 20 (20 MOI). These cell lines were regarded as being highly sensitive cells. The cell viability of a nonmalignant immortalized cell line, OUMS-24, was not inhibited at 200 MOI of Ad-REIC. The effects of Ad-REIC on EGFR-TKI resistant sublines were equivalent to those in the parental cell lines. Here, we demonstrated that Ad-REIC treatment activated c-Jun N-terminal kinase (JNK) in NSCLC cell lines, indicating the induction of ER stress with GRP78/BiP (GRP78) up-regulation and resulting in apoptosis. A single intratumoral injection of Ad-REIC significantly inhibited the tumorigenic growth of A549 cells in vivo. As predictive factors of sensitivity for Ad-REIC treatment in NSCLC, we examined the expression status of GRP78 and coxsackievirus and adenovirus receptor (CAR). We found that the combination of the GRP78 and CAR expressional statuses may be used as a predictive factor for Ad-REIC sensitivity in NSCLC cells.
    Conclusion: Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells. Our study indicated that Ad-REIC has therapeutic potential against NSCLC and that the expression statuses of GRP78 and CAR may predict a potential therapeutic benefit of Ad-REIC.

    DOI: 10.1371/journal.pone.0087900

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  • N’-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide is a dynamin GTPase inhibitor that suppresses cancer cell migration and invasion by inhibiting actin polymerization . 査読

    Hiroshi Yamada, Tadashi Abe, Shun-Ai Li, Shota Tago, Peng Huang, Masami Watanabe, Satoru Ikeda, Naohisa Ogo, Akira Asai, Kohji Takei

    Biochem Biophys Res Commun   443 ( 2 )   511 - 517   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A rare complication: Misdirection of an indwelling urethral catheter into the ureter 査読

    Tsutomu Ishikaw, Motoo Araki, Takeshi Hirata, Masami Watanabe, Shin Ebara, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

    Acta Medica Okayama   68 ( 1 )   47 - 51   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report 3 patients with the rare complication of an indwelling urethral catheter misdirected into the ureter. This is the largest series to date. Patients were referred to us for a variety of reasons following exchange of their chronic indwelling urinary catheters. CT in all cases demonstrated the urinary catheters residing in the left ureter. The ages of the patients were 37, 67 and 81 years old. All patients suffered from neurogenic bladder. Two patients were female, one was male, and 2 of the 3 had a sensory disorder inhibiting their pain response. The catheters were replaced with open-end Foley catheters. Extensive follow-up CT scans were obtained in one case, demonstrating improvement of hydronephrosis and no evidence of ureteral stenosis. Cystoscopy in this patient demonstrated normally positioned and functioning ureteral orifices. Although the placement of an indwelling urethral catheter is a comparatively safe procedure, one must keep in mind that this complication can occur, particularly in female patients with neurogenic bladder. CT without contrast is a noninvasive, definitive diagnostic tool. © 2014 by Okayama University Medical School.

    DOI: 10.18926/AMO/52144

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  • Comparison of New Preservation Solutions, HN-1 and University of Wisconsin Solution, in Pancreas Preservation for Porcine Islet Isolation. 査読

    Katayama Akihiro, Noguchi Hirofumi, Kuise Takashi, Nakatsuka Atsuko, Hirota Daisho, Kataoka Hitomi, Kawai Takashi, Inoue Kentaro, Imagawa Noriko, Saitoh Issei, Noguchi Yasufumi, Watanabe Masami, Wada Jun, Fujiwara Toshiyoshi

    Cell Medicine   2013年12月

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    記述言語:英語  

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  • Testosterone replacement elevates the serum uric acid levels in patients with female to male gender identity disorder 査読

    Hiroaki Kurahashi, Masami Watanabe, Morito Sugimoto, Yuichi Ariyoshi, Sabina Mahmood, Motoo Araki, Kazushi Ishii, Yasutomo Nasu, Atsushi Nagai, Hiromi Kumon

    ENDOCRINE JOURNAL   60 ( 12 )   1321 - 1327   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN ENDOCRINE SOC  

    Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.

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  • Comparison of incubation solutions prior to the purification of porcine islet cells. 査読

    Kawai Takashi, Noguchi Hirofumi, Kuise Takashi, Nakatsuka Atsuko, Katayama Akihiro, Imagawa Noriko, Kataoka, Hitomi Usui, Saitoh Issei, Noguchi Yasufumi, Watanabe Masami, Fujiwara Toshiyoshi

    Cell Medicine   2013年10月

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    記述言語:英語  

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  • Molecular cloning and tumour suppressor function analysis of canine REIC/Dkk-3 in mammary gland tumours 査読

    Kazuhiko Ochiai, Masami Watanabe, Daigo Azakami, Masaki Michishita, Yasunaga Yoshikawa, Chihiro Udagawa, Pornphimon Metheenukul, Thippayarat Chahomchuen, Hiroshi Aoki, Hiromi Kumon, Masami Morimatsu, Toshinori Omi

    VETERINARY JOURNAL   197 ( 3 )   769 - 775   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    REIC/Dkk-3, a member of the human Dickkopf (Dkk) family, plays a role as a suppressor of growth in several human cancers. In this study, the tumour suppression function of canine REIC/Dkk-3 was investigated. The full-length open reading frame of the canine REIC/Dkk-3 homologue was cloned and the tissue distribution of REIC/Dkk-3 mRNA was determined, along with the subcellular localisation of the REIC/Dkk-3 protein in canine cancer cell lines. Expression of REIC/Dkk-3 was lower in mammary gland tumours and in canine mammary carcinoma cell lines than in normal mammary gland tissue. Overexpression of REIC/Dkk-3 induced apoptosis in canine mammary carcinoma cell lines. These results show that expression of REIC/Dkk-3 is downregulated in canine mammary tumours and that one of the functions of this gene is induction of apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.

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  • Clinical significance of CD24 as a predictor of bladder cancer recurrence 査読

    Chunxiao Liu, Shaobo Zheng, Haiyan Shen, Kai Xu, Jie Chen, Hulin Li, Yawen Xu, Abai Xu, Binshen Chen, Haruki Kaku, Yasutomo Nasu, Hiromi Kumon, Peng Huang, Masami Watanabe

    ONCOLOGY LETTERS   6 ( 1 )   96 - 100   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Cluster of differentiation (CD)24 was originally described as a B lymphocyte marker and has recently received considerable attention in cancer research as its overexpression has been observed in several types of carcinoma. The CD24 molecule is a glycosyl-phosphatidylinositol-linked cell surface protein that appears to be associated with aggressive cancers involving invasion and metastasis. However, the expression of CD24 in human bladder cancer and its clinical significance remains largely unknown and no association has been reported between CD24 overexpression and human bladder tumor recurrence. In the present study, the CD24 expression in cancer tissues obtained during transurethral surgery and the subsequent intra-bladder tumor recurrence following surgery were assessed. Immunohistochemical staining was performed and the intensity of CD24 staining was semi-quantitatively evaluated. CD24 expression was observed more frequently in high-grade bladder tumors (G2-G3) than low-grade tumors (G1). Positive CD24 expression was significantly associated with intra-bladder tumor recurrence following surgery and increased staining intensity was also correlated with recurrence. The positive association between CD24 expression and tumor recurrence was observed in each tumor category (stages Ta and Tl, low and high grade). The results demonstrated that CD24 expression is Significantly associated with bladder tumor recurrence. To the best of our knowledge, this is the first study to reveal the significance of CD24 as a predictor of bladder cancer recurrence. These insights may lead to future therapeutic strategies targeting CD24 to prevent the dissemination of bladder cancer cells and tumor recurrence.

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  • Stabilization of actin bundles by a dynamin 1/cortactin ring complex is necessary for growth cone filopodia. 査読 国際誌

    Hiroshi Yamada, Tadashi Abe, Ayano Satoh, Nana Okazaki, Shota Tago, Kinue Kobayashi, Yumi Yoshida, Yoshiya Oda, Masami Watanabe, Kazuhito Tomizawa, Hideki Matsui, Kohji Takei

    The Journal of neuroscience : the official journal of the Society for Neuroscience   33 ( 10 )   4514 - 26   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dynamin GTPase, a key molecule in endocytosis, mechanically severs the invaginated membrane upon GTP hydrolysis. Dynamin functions also in regulating actin cytoskeleton, but the mechanisms are yet to be defined. Here we show that dynamin 1, a neuronal isoform of dynamin, and cortactin form ring complexes, which twine around F-actin bundles and stabilize them. By negative-staining EM, dynamin 1-cortactin complexes appeared as "open" or "closed" rings depending on guanine nucleotide conditions. By pyrene actin assembly assay, dynamin 1 stimulated actin assembly in mouse brain cytosol. In vitro incubation of F-actin with both dynamin 1 and cortactin led to the formation of long and thick actin bundles, on which dynamin 1 and cortactin were periodically colocalized in puncta. A depolymerization assay revealed that dynamin 1 and cortactin increased the stability of actin bundles, most prominently in the presence of GTP. In rat cortical neurons and human neuroblastoma cell line, SH-SY5Y, both dynamin 1 and cortactin localized on actin filaments and the bundles at growth cone filopodia as revealed by immunoelectron microscopy. In SH-SY5Y cell, acute inhibition of dynamin 1 by application of dynamin inhibitor led to growth cone collapse. Cortactin knockdown also reduced growth cone filopodia. Together, our results strongly suggest that dynamin 1 and cortactin ring complex mechanically stabilizes F-actin bundles in growth cone filopodia. Thus, the GTPase-dependent mechanochemical enzyme property of dynamin is commonly used both in endocytosis and regulation of F-actin bundles by a dynamin 1-cortactin complex.

    DOI: 10.1523/JNEUROSCI.2762-12.2013

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  • Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder 査読

    Aya Nakamura, Masami Watanabe, Morito Sugimoto, Tomoko Sako, Sabina Mahmood, Haruki Kaku, Yasutomo Nasu, Kazushi Ishii, Atsushi Nagai, Hiromi Kumon

    ENDOCRINE JOURNAL   60 ( 3 )   275 - 281   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN ENDOCRINE SOC  

    Gender identity disorder (GID) is a conflict between a person's actual physical gender and the one they identify him or herself with. Testosterone is the key agent in the medical treatment of female to male GID patients. We conducted a dose-response analysis of testosterone replacement therapy (TRT) in 138 patients to determine the onset of the therapeutic effects. The TRT consisted of intramuscular injection of testosterone enanthate and patients were divided into three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every two weeks. The onset of deepening of voice, increase in facial hair and cessation of menses was evaluated in each group. At one month after the start of TRT, the onset of these physical changes was more prevalent in the group receiving the higher dose of testosterone, and there were dose-dependent effects observed between the three treatment groups. On the other hand, at six months after the start of TRT, most of the patients had achieved treatment responses and there were no dose-dependent effects with regard to the percentage of patients with therapeutic effects. No significant side effects were observed in any of the treatment groups. We demonstrated that the early onset of the treatment effects of TRT is dose-dependent, but within six months of starting TRT, all three doses were highly effective. Current study provides useful information to determine the initial dose of TRT and to suggest possible changes that should be made in the continuous dosage for long term TRT.

    DOI: 10.1507/endocrj.EJ12-0319

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  • In Vivo Imaging of Transplanted Islets Labeled with a Novel Cationic Nanoparticle 査読

    Koichi Oishi, Yoshitaka Miyamoto, Hiroaki Saito, Katsutoshi Murase, Kenji Ono, Makoto Sawada, Masami Watanabe, Yasufumi Noguchi, Toshiyoshi Fujiwara, Shuji Hayashi, Hirofumi Noguchi

    PLoS ONE   8 ( 2 )   2013年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To monitor pancreatic islet transplantation efficiency, reliable noninvasive imaging methods, such as magnetic resonance imaging (MRI) are needed. Although an efficient uptake of MRI contrast agent is required for islet cell labeling, commercially-available magnetic nanoparticles are not efficiently transduced into cells. We herein report the in vivo detection of transplanted islets labeled with a novel cationic nanoparticle that allowed for noninvasive monitoring of islet grafts in diabetic mice in real time. The positively-charged nanoparticles were transduced into a β-cell line, MIN6 cells, and into isolated islets for 1 hr. MRI showed a marked decrease in the signal intensity on T1- and T2-weighted images at the implantation site of the labeled MIN 6 cells or islets in the left kidneys of mice. These data suggest that the novel positively-charged nanoparticle could be useful to detect and monitor islet engraftment, which would greatly aid in the clinical management of islet transplant patients. © 2013 Oishi et al.

    DOI: 10.1371/journal.pone.0057046

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  • Culture conditions for mouse pancreatic stem cells. 査読

    Noguchi H, Saitoh I, Kataoka HU, Watanabe M, Fujiwara T

    Cell Medicine.   5   63 - 68   2013年1月

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    記述言語:英語  

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  • Isolation efficiency of mouse pancreatic stem cells is age-dependent. 査読

    Kuise T, Noguchi H, Saitoh I, Kataoka HU, Watanabe M, Fujiwara T

    Cell Medicine.   5   69 - 73   2013年1月

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    記述言語:英語  

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  • Cancer stem cell-like characteristics of a CD133+ subpopulation in the J82 human bladder cancer cell line. 査読 国際誌

    Peng Huang, Masami Watanabe, Haruki Kaku, Hideo Ueki, Hirofumi Noguchi, Morito Sugimoto, Takeshi Hirata, Hiroshi Yamada, Kohji Takei, Shaobo Zheng, Kai Xu, Yasutomo Nasu, Yasuyuki Fujii, Chunxiao Liu, Hiromi Kumon

    Molecular and clinical oncology   1 ( 1 )   180 - 184   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cancer stem cells (CSCs) are thought to be crucial for understanding the biological roots of cancer, and are of increasing importance as a target for new anticancer agents. According to an expression analysis of the cell surface antigens of various types of cancer, CD133 is considered to be a potential marker of cancer stemness. In this study, a human urinary bladder cancer cell line (J82) was used to analyze the cancer stem cell-like characteristics of CD133+ bladder cancer cells in vitro and in vivo. The CD133 expression in the J82 cells was examined and the cells were immunomagnetically categorized into positive and negative subsets. The CD133- and CD133+ subsets were phenotypically divergent with regard to the cell growth pattern, while CD133+ cells tended to colonize during their growth. In CD133+ cells, the pluripotent stem cell factors Oct-4 and Sox-2 were upregulated, and a statistically significant proliferation increase was observed when compared to CD133- cells. The CD133+ subpopulation was more tolerant to the chemotherapeutic agent cisplatin, and Bacillus Calmette-Guérin (BCG), an agent instilled intravesically to treat bladder cancer. In addition, CD133+ J82 cells were more resistant to radiation treatment when compared to CD133- cells. The in vivo tumorigenesis of the CD133- and CD133+ subsets of J82 cancer cells was also examined by subcutaneously injecting them into nude mice. The tumor growth was more aggressive in the CD133+ subpopulation, showing a significant difference in the tumorigenic potential in these subsets. In conclusion, J82 human bladder cancer cells include CD133- and CD133+ subpopulations, while the CD133 molecule is a potential marker of the potential malignancy of human bladder cancer. In the present study, the CD133+ subpopulation was herein demonstrated to have certain characteristics consistent with those of cancer stem cells.

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  • DIRECT THERAPEUTIC EFFECT OF REIC/DKK-3-ENCODING ADENOVIRAL VECTOR FOR NON-SMALL CELL LUNG CANCER 査読

    Yamamoto Hiromasa, Tanaka Norimitsu, Toyooka Shinichi, Watanabe Masami, Sakaguchi Masakiyo, Soh Junichi, Shien Kazuhiko, Furukawa Masashi, Asano Hiroaki, Tsukuda Kazunori, Nasu Yasutomo, Huh Nam-ho, Kumon Hiromi, Miyoshi Shinichirou

    JOURNAL OF THORACIC ONCOLOGY   7 ( 11 )   S463   2012年11月

  • Preclinical biodistribution and safety study of reduced expression in immortalized cells/Dickkopf-3-encoding adenoviral vector for prostate cancer gene therapy 査読

    Morito Sugimoto, Masami Watanabe, Haruki Kaku, Shun-Ai Li, Hirofumi Noguchi, Hideo Ueki, Masakiyo Sakaguchi, Nam-Ho Huh, Yasutomo Nasu, Hiromi Kumon

    ONCOLOGY REPORTS   28 ( 5 )   1645 - 1652   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The biodistribution and safety of adenoviral vectors encoding the human REIC/Dkk-3 tumor suppressor gene (Ad-REIC) were examined in this preclinical study for in situ prostate cancer gene therapy. First, the in vitro apoptotic effects of Ad-REIC in normal and cancer cells derived from the prostate and liver were examined. Significant apoptotic effects were observed at 100 MOI (multiplicity of infection) in prostate cancer cells (LNCaP, PC3) and hepatoma cells (HEP3B and HEPG2); however, no effects were seen in normal cells. To analyze the safety of intraprostatic Ad-REIC administration, the biodistribution and histology after Ad-REIC injection were evaluated in various organs of normal male C57BL6 mice. In a supporting study, vector dissemination following intravenous injection of Ad-REIC into tail veins was determined. To evaluate whether Ad-REIC was present in the collected tissue specimens, human REIC gene detection was performed using DNA-PCR. Intraprostatic treatment administered at lower doses showed vector biodistribution into the colon, urinary bladder and prostate. At higher doses, vector dissemination was observed in tissues more distant from the prostate, including the lung, thymus, heart, liver and adrenal gland. After intravenous injection a: Ad-REIC, dissemination was observed in the liver and spleen. These results indicate that the biodistribution of Ad-REIC is determined by the dose and route of administration. Although acute inflammatory effects were observed in the prostate after intraprostatic administration at higher doses, no abnormal histological findings were noted in the other tissues, including those of intravenously treated mice. Regarding the safety of Ad-REIC administration, no deaths and no signs of toxicity or unusual behavior were observed in the mice in any treatment group. Based on these preclinical experiments, adenovirus-mediated in situ REIC/Dkk-3 gene therapy is considered to be safe for use as a treatment for human prostate cancer.

    DOI: 10.3892/or.2012.2001

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  • REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer 査読

    Takeshi Hirata, Masami Watanabe, Haruki Kaku, Yasuyuki Kobayashi, Hiroshi Yamada, Masakiyo Sakaguchi, Kohji Takei, Nam-Ho Huh, Yasutomo Nasu, Hiromi Kumon

    INTERNATIONAL JOURNAL OF ONCOLOGY   41 ( 2 )   559 - 564   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Bladder cancer is one of the most common urogenital malignancies. The intravesical instillation of anticancer agents is an attractive strategy to treat a superficial lesion or floating/disseminated cancer cells after transurethral operation. An adenovirus carrying REIC/Dkk-3, a tumor suppressor gene (Ad-REIC), exhibits cancer-specific apoptotic effects in various types of cancer cells. The aim of the present study was to examine the potential of Ad-REIC as a therapeutic agent for bladder cancer. KK47 and RT4 human bladder cancer cells were sensitive to the Ad-REIC treatment for apoptosis induction, but some human bladder cancer cell lines (T24, J82 and TccSup) were resistant. Significant cell growth inhibition was observed when these resistant cancer cell lines were treated with Ad-REIC in a condition of floating cells, which is clinically observed after transurethral operation and becomes a cause of intravesical cancer dissemination. The therapeutic potential of Ad-REIC for the treatment of multidrug-resistant bladder cancer was investigated. The adriamycin-resistant KK47 bladder cancer cells (KK47/ADM), which also present multidrug resistance, showed induction of significant apoptosis following Ad-REIC treatment. The Ad-REIC treatment induced downregulation of P-glycoprotein in KK47/ADM cells and restored the sensitivity to doxorubicin (adriamycin). Ad-REIC suppressed P-glycoprotein expression in a c-Jun-NH2-kinase (JNK)-dependent manner. Therefore, the current study indicated two therapeutic aspects of the Ad-REIC agent against human bladder cancer cells, as an apoptosis inducer/cell growth inhibitor and as a sensitizer of chemotherapeutic agents in multidrug-resistant cancer cells. The intravesical instillation of Ad-REIC could be an attractive therapeutic method in human bladder cancer where the treatment of superficial lesions and floating/disseminated or multidrug-resistant cancer cells is necessary.

    DOI: 10.3892/ijo.2012.1503

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  • A novel gene expression system for detecting viable bladder cancer cells 査読

    Hideo Ueki, Masami Watanabe, Haruki Kaku, Peng Huang, Shun-Ai Li, Kazuhiko Ochiai, Takeshi Hirata, Hirofumi Noguchi, Hiroshi Yamada, Kohji Takei, Yasutomo Nasu, Yuji Kashiwakura, Hiromi Kumon

    INTERNATIONAL JOURNAL OF ONCOLOGY   41 ( 1 )   135 - 140   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    A novel transcriptional system was developed that can robustly enhance cancer-specific gene expression. In the system, hTERT promoter-driven gene expression was enhanced by an advanced two-step transcriptional amplification (TSTA). This construct was used to develop a novel system for detection of bladder cancer cells. The current study evaluated the advanced TSTA system by examining the cancer-specific gene transcription in various bladder cancer cell lines. The system significantly enhanced cancer-specific luciferase gene expression in the bladder cancer cell lines in comparison to the previous expression system of one-step or conventional TSTA. The fold gain of the enhancement was significantly correlated to the telomerase activity of the cell lines. A green fluorescent protein (GFP) gene encoding plasmid vector was constructed where hTERT promoter-driving transcription is enhanced by the advanced TSTA to utilize the system for the imaging and detection of viable bladder cancer cells. The advanced TSTA-hTERT-GFP plasmid successfully induced cancer-specific gene expression, showing robust GFP expression in human bladder cancer cell lines, but no visible GFP expression in normal bladder urothelial cells. The control GFP plasm id with a CMV promoter yielded GFP expression in both normal bladder cells and cancer cells. The advanced TSTA-hTERT-GFP plasmid allowed selective visualization of viable human bladder cancer cells in mixed cell culture containing 10- and 100-fold more normal bladder urothelial cells. These findings indicate that the advanced TSTA-hTERT expressional system is a valuable tool for detecting viable bladder cancer cells. The current system can be applied for in vitro detection of bladder cancer cells in urine and other types of cancer cells disseminated in vivo.

    DOI: 10.3892/ijo.2012.1417

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  • Implications of transcriptional factor, OCT-4, in human bladder malignancy and tumor recurrence 査読

    Peng Huang, Jie Chen, Lei Wang, Yanqun Na, Haruki Kaku, Hideo Ueki, Katsumi Sasaki, Ken Yamaguchi, Kai Zhang, Takashi Saika, Yasutomo Nasu, Masami Watanabe, Hiromi Kumon

    MEDICAL ONCOLOGY   29 ( 2 )   829 - 834   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    OCT-4, which is also known as POU5f1, is a key regulator of self-renewal in embryonic stem cells. The new cancer stem cell concept proposes that the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of the cancer behavior, such as recurrence or metastasis. This study investigated the association between OCT-4 expression in cancer tissues obtained by transurethral surgery and the clinical data to clarify the involvement of OCT-4 in human bladder malignancy. Immunohistochemical analysis demonstrated that a positive rate of OCT-4 expression was significantly associated with the higher-grade cancer (G2 and G3) in comparison with that of the lower grade (G1). In addition, positive OCT-4 expression was significantly associated with the intra-bladder tumor recurrence after the operation. The staining intensity of OCT-4 expression was also correlated with tumor recurrence. These data indicate that positive OCT-4 expression may be involved in the development of high-grade bladder cancer and with the bladder cancer recurrence. This is the first study showing a correlation between the expression of OCT-4 and bladder cancer recurrence. OCT-4 may be a valuable clinical marker for the progression of bladder cancer and may be an attractive therapeutic target for the development of new medicines for the treatment of malignancy.

    DOI: 10.1007/s12032-011-9962-4

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  • 非小細胞肺癌に対する新たな個別化治療戦略 REIC/Dkk-3遺伝子治療の可能性

    宗 淳一, 豊岡 伸一, 田中 則光, 渡部 昌実, 山本 寛斉, 阪口 政清, 許 南浩, 那須 保友, 公文 裕巳, 三好 新一郎

    日本呼吸器外科学会雑誌   26 ( 3 )   P17 - 01   2012年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1 査読

    Yu Jin, Hitoshi Murata, Masakiyo Sakaguchi, Ken Kataoka, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

    ONCOLOGY REPORTS   27 ( 3 )   695 - 699   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    REIC/Dkk-3 is a tumor suppressor gene that was first identified as a gene downregulated in association with immortalization of normal human fibroblasts. We have demonstrated that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) showed a tumor-specific killing effect on a wide range of cancers. However, some human cancers, bladder cancers in particular, are resistant to Ad-REIC. In this study, we investigated the combination effect of downregulation of BRPK/PINK1 (PINK1) and Ad-REIC on bladder cancer cells. Five bladder cancer cell lines among six cell lines examined were resistant to Ad-REIC. Among the cell lines, the resistance of two cell lines was probably due to low infection efficiency of the adenovirus. PINK1-specific siRNA remarkably downregulated Bcl-x(L) and TRAP1 proteins and upregulated BAX protein expression. Finally, downregulation of PINK1 partially sensitized the other three cell lines that were resistant to Ad-REIC. This sensitization was associated with increasing production of reactive oxygen species (ROS). These results indicate that PINK1 is one of the key molecules for the mitochondrial protection system and that PINK1 can be a new target molecule to sensitize bladder cancer cells that are resistant to Ad-REIC.

    DOI: 10.3892/or.2011.1543

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  • Preclinical Safety and Efficacy of in Situ REIC/Dkk-3 Gene Therapy for Prostate Cancer 査読

    Keiichiro Kawauchi, Masami Watanabe, Haruki Kaku, Peng Huang, Kasumi Sasaki, Masakiyo Sakaguchi, Kazuhiko Ochiai, Nam-ho Huh, Yasutomo Nasu, Hiromi Kumon

    ACTA MEDICA OKAYAMA   66 ( 1 )   7 - 16   2012年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer.

    DOI: 10.18926/AMO/48076

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  • Single Nucleotide Polymorphism WRN Leu1074Phe Is Associated with Prostate Cancer Susceptibility in Chinese Subjects 査読

    Lei Wang, Haruki Kaku, Peng Huang, Kexin Xu, Kai Yang, Jiheng Zhang, Ming Li, Liping Xie, Xiaofeng Wang, Akiko Sakai, Masami Watanabe, Yasutomo Nasu, Kenji Shimizu, Hiromi Kumon, Yanqun Na

    ACTA MEDICA OKAYAMA   65 ( 5 )   315 - 323   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR = 0.58, 95% CI: 0.35-0.97, p = 0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age <= 72 yr (OR = 0.27, 95% CI: 0.12-0.61, p = 0.002) and in patients with localized diseases (OR = 0.36, 95% CI: 0.19-0.70, p = 0.003). However, no statistically significant difference was found in the subgroup with age > 72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects.

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  • Advanced two-step transcriptional amplification as a novel method for cancer-specific gene expression and imaging 査読

    Masami Watanabe, Hideo Ueki, Kazuhiko Ochiai, Peng Huang, Yasuyuki Kobayashi, Yasutomo Nasu, Katsumi Sasaki, Haruki Kaku, Yuji Kashiwakura, Hiromi Kumon

    ONCOLOGY REPORTS   26 ( 4 )   769 - 775   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The two-step transcriptional amplification (TSTA) system was previously reported to enhance the tissue-specific gene expression driven by weak promoters, but the enhancement of the gene expression is limited to use in in vitro and in vivo experimental situations. To achieve robust tissue-specific gene expression using the TSTA system, we developed an advanced TSTA system which includes polyglutamines and rat glucocorticoid receptor sequences between the GAL4 and VP16 sequences in the region of the first step of transcription. We evaluated the advanced TSTA system as a method to enhance the human telomerase reverse transcriptase (hTERT) promoter-driving cancer-specific transcription in various cancer cell lines. As a result, the advanced TSTA enhanced cancer-specific luciferase gene expression in all of the examined cancer cell lines, when compared with both the one-step and conventional TSTA systems (an similar to 6- and similar to 17-fold enhancement, respectively). Notably, the enhancement of the hTERT driven expression by the conventional TSTA system was modest and even inferior to the one-step system in several cancer cell lines. We then constructed a luciferase gene encoding the adeno-associated virus vector in which the hTERT promoter-mediated expression was driven by the advanced TSTA or control systems. In an orthotopic liver tumor model, mice were treated with the vector via tail vein injection. An optical imaging device was used to visualize the in vivo luciferase expression in the orthotopic tumor. The advanced TSTA system significantly enhanced the luciferase expression compared with the one-step and conventional TSTA systems (18.0+/-1.0- and 15.9+/-0.85-fold gain, respectively). Therefore, the advanced TSTA system significantly improves hTERT-dependent cancer-specific gene expression both in vitro and in vivo when compared with the previous systems. Since the advanced TSTA method can also be applied to other site-specific gene expression systems using tissue-specific promoters, this approach is expected to become a valuable tool enabling in vivo site-specific targeting in the field of gene therapy and molecular imaging.

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  • Tumor growth and metastasis suppression by Glipr1 gene-modified macrophages in a metastatic prostate cancer model 査読

    K. Tabata, S. Kurosaka, M. Watanabe, K. Edamura, T. Satoh, G. Yang, E. Abdelfattah, J. Wang, A. Goltsov, D. Floryk, T. C. Thompson

    GENE THERAPY   18 ( 10 )   969 - 978   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We previously identified the mouse and human Glipr1 and GLIPR1/RTVP-1 genes, respectively, as direct p53 targets with proapoptotic activities in various cancer cell lines, including prostate cancer (PCa). Intratumoral injection of an adenoviral vector capable of efficient transduction and expression of Glipr1 (AdGlipr1) yielded promising therapeutic results in an orthotopic, metastatic mouse model of PCa. AdGlipr1-transduced macrophages (M phi/Glipr1) generated greater surface expression of CD40, CD80 and major histocompatibility complex class II molecules and greater production of interleukin 12 (IL-12) and IL-6 in vitro than control macrophages did. Mechanistic analysis indicated that increased production of IL-12 in M phi/Glipr1 depends on activation of the p38 signaling cascade. M phi/Glipr1 injected into orthotopic 178-2BMA tumors in vivo resulted in significantly suppressed prostate tumor growth and spontaneous lung metastases and longer survival relative to those observed in control-treated mice. Furthermore, these preclinical data indicate the generation of systemic natural killer cell activity and tumor-specific cytotoxic T lymphocyte responses. Trafficking studies confirmed that intratumorally injected M phi/Glipr1 could migrate to draining lymph nodes. Overall, our data suggest that this novel gene-modified cell approach is an effective treatment avenue that induces antitumor immune responses in preclinical studies. Gene Therapy (2011) 18, 969-978; doi:10.1038/gt.2011.51; published online 21 April 2011

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  • Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1 査読

    Kazuhiko Ochiai, Masami Watanabe, Hideo Ueki, Peng Huang, Yasuyuki Fujii, Yasutomo Nasu, Hirofumi Noguchi, Takeshi Hirata, Masakiyo Sakaguchi, Nam-ho Huh, Yuji Kashiwakura, Haruki Kaku, Hiromi Kumon

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   412 ( 2 )   391 - 395   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    REIC/Dkk-3 is a member of the Dickkopf family proteins known as Wnt-antagonists, and REIC/Dkk-3 expression is downregulated in a broad range of cancer types. REIC/Dkk-3 acts as a tumor suppressor in multiple cancer cell lines by inducing apoptosis through endoplasmic reticulum (ER) stress signaling. However, the intracellular interaction partners of REIC/Dkk-3 have not been fully elucidated. By employing yeast two-hybrid screening, we identified the human dynein light chain, Tctex-1, as a novel interaction partner of REIC/Dkk-3. We further disclosed that the interaction involves the 136-157 amino acid region of REIC/Dkk-3 by using the mammalian two-hybrid system. Interestingly, this binding region of REIC/Dkk-3 with Tctex-1 contains an amino acid sequence motif [-(E) under bar -X-(G) under bar-(R) under bar-(R) under bar -X-(H) under bar-] which was previously reported as the Tctex-1 binding domain of dynein intermediate chain (DIC). Immunocytochemistry demonstrated that both REIC/Dkk-3 and Tctex-1 were localized around the ER of human fibroblasts, and the similar distribution pattern of the proteins suggests that their interaction occurs around the ER. This is the first study showing the interaction of a Dickkopf family protein with a dynein motor complex protein. The link between REIC/Dkk-3 and Tctex-1 may be of significance for understanding the molecular functions of the proteins in ER stress signaling and intracellular dynein motor dynamics, respectively. (C) 2011 Elsevier Inc. All rights reserved.

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  • [REIC/Dkk-3 gene therapy]. 査読

    Masami Watanabe, Haruki Kaku, Peng Huang, Hiromi Kumon, Yasutomo Nasu

    Nihon rinsho. Japanese journal of clinical medicine   69 Suppl 5   559 - 63   2011年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • A PHASE I/II STUDY OF ADENOVIRUS-MEDIATED INTERLEUKIN-12 GENE THERAPY FOR HORMONE REFRACTORY PROSTATE CANCER; A REPORT OF INITIAL 6 CASES 査読

    Sasaki Katsumi, Nasu Yasutomo, Kaku Haruki, Watanabe Masami, Edamura Kohei, Saika Takashi, Kumon Hiromi, Brenner Malcolm K

    JOURNAL OF GENE MEDICINE   12 ( 12 )   1025   2010年12月

  • Expression pattern of REIC/Dkk-3 in various cell types and the implications of the soluble form in prostatic acinar development 査読

    Kai Zhang, Masami Watanabe, Yuji Kashiwakura, Shun-Al Li, Kohei Edamura, Peng Huang, Ken Yamaguchi, Yasutomo Nasu, Yasuyuki Kobayashi, Masakiyo Sakaguchi, Kazuhiko Ochiai, Hiroshi Yamada, Kohji Takei, Hideo Ueki, Nam-Ho Huh, Ming Li, Haruki Kaku, Yanqun Na, Hiromi Kumon

    INTERNATIONAL JOURNAL OF ONCOLOGY   37 ( 6 )   1495 - 1501   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The tumor suppressor REIC/Dkk-3 is a secretory protein which was originally identified to be downregulated in human immortalized cells In the present study, we investigated the expression pattern of REIC/Dkk-3 in various cell types to characterize its physiological functions We first examined the expression level of REIC/Dkk-3 in a broad range of cancer cell types and confirmed that it was significantly downregulated in all of the cell types We also examined the tissue distribution pattern in a variety of normal mouse organs Ubiquitous REIC/Dkk-3 protein expression was observed in the organs The expression was abundant in the liver, heart and brain tissue, but was absent in the spleen and peripheral blood mononuclear cells The immunohistochemical analyses revealed that the subcellular localization of REIC/Dkk-3 had a punctate pattern around the nucleus, indicating its association with secretory vesicles In cancer cells stably transfected with REIC/Dkk-3 the protein was predominantly localized to the endoplasmic reticulum (ER) under observation with confocal microscopy Because REIC/ Dkk-3 was found to be abundantly expressed in the acinar epithelial cells of the mouse prostate, we analyzed the effects of recombinant REIC/Dkk-3 protein on the acinar morphogenesis of RWPE-1 cells, which are derived from human normal prostate epithelium Statistically significant acinar growth was observed in the culture condition with 10 mu g/m1 REIC/Dkk-3 protein, implicating the soluble form m prostatic acinar development Current results suggest that REIC/Dkk-3 may play a role in regulating the morphological process of normal tissue architecture through an autocrine and/or paracrine manner

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  • Potent antitumor effects of combined therapy with a telomerase-specific, replication-competent adenovirus (OBP-301) and IL-2 in a mouse model of renal cell carcinoma 査読

    P. Huang, H. Kaku, J. Chen, Y. Kashiwakura, T. Saika, Y. Nasu, Y. Urata, T. Fujiwara, M. Watanabe, H. Kumon

    CANCER GENE THERAPY   17 ( 7 )   484 - 491   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    OBP-301 (a telomerase-specific, replication-competent adenovirus with hTERT promoter) was constructed in a previous study and it showed a strong anticancer effect by inducing cell lysis in human lung and prostate cancer cells. This study investigated the effectiveness of a combination therapy of OBP-301 and interleukin-2 (IL-2) in a mouse model of renal cell carcinoma (RCC). The cell-killing effect of OBP-301 was confirmed in vitro in the RENCA cancer cells. In in vivo experiment, luciferase-expressing RENCA cells were implanted in the left kidney and lung of BALB/c mice to prepare the RCC metastatic model. The animals were randomly divided into four treatment groups: PBS, IL-2 alone, OBP-301 alone and the combination. The analyses of orthotopic tumor weight, lung metastasis and luciferin-stained tumor images 14 days after each treatment showed significant tumor growth inhibition in the combination group in comparison with that in the OBP-301- or IL-2-treated groups. In addition, the percentage of regulatory T-cells (Tregs) in the combination group was significantly suppressed in comparison with that in the PBS and single-agent treatment groups. The outcomes of this study suggest that tumor-specific oncolytic immunovirotherapy may become an attractive strategy for the treatment of human RCC. Cancer Gene Therapy (2010) 17, 484-491; doi:10.1038/cgt.2010.5; published online 19 February 2010

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  • The role of caveolin-1 in prostate cancer: clinical implications 査読

    T. C. Thompson, S. A. Tahir, L. Li, M. Watanabe, K. Naruishi, G. Yang, D. Kadmon, C. J. Logothetis, P. Troncoso, C. Ren, A. Goltsov, S. Park

    PROSTATE CANCER AND PROSTATIC DISEASES   13 ( 1 )   6 - 11   2010年3月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    Caveolin-1 (cav-1) is reportedly overexpressed in prostate cancer cells and is associated with disease progression. Specific oncogenic activities of cav-1 associated with Akt activation also occur in prostate cancer. A membrane-associated protein, cav-1, is nonetheless secreted by prostate cancer cells; results of recent studies showed that secreted cav-1 can stimulate cell survival and angiogenic activities, defining a role for cav-1 in the prostate cancer microenvironment. Serum cav-1 levels were also higher in prostate cancer patients than in control men without prostate cancer, and the preoperative serum cav-1 concentration had prognostic potential in men undergoing radical prostatectomy. Secreted cav-1 is therefore a potential biomarker and therapeutic target for prostate cancer. Prostate Cancer and Prostatic Diseases (2010) 13, 6-11; doi:10.1038/pcan.2009.29; published online 7 July 2009

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  • Dynasore, a dynamin inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments 査読

    Hiroshi Yamada, Tadashi Abe, Shun-Ai Li, Yuki Masuoka, Mihoko Isoda, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Akira Asai, Kohji Takei

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   390 ( 4 )   1142 - 1148   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Dynamic remodeling of actin filaments are bases for a variety of cellular events including cell motility and cancer invasion, and the regulation of actin dynamics implies dynamin, well characterized endocytotic protein. Here we report that dynasore, a inhibitor of dynamin GTPase, potently destabilizes F-actin in vitro, and it severely inhibits the formation of pseudopodia and cancer cell invasion, both of which are supported by active F-actin formation. Dynasore rapidly disrupted F-actin formed in brain cytosol in vitro, and the dynasore's effect on F-actin was indirect. Dynasore significantly suppressed serum-induced lamellipodia formation in U2OS cell. Dynasore also destabilized F-actin in resting cells, which caused the retraction of the plasma membrane. A certain amount of dynamin 2 in U2OS cells localized along F-actin, and co-localized with cortactin, a physiological binding partner of dynamin and F-actin. However. these associations of dynamin were partially disrupted by dynasore treatment. Furthermore, invasion activity of H1080 cell, a lung cancer cell line, was suppressed by approximately 40% with dynasore treatment. These results strongly suggest that dynasore potently destabilizes F-actin, and the effect implies dynamin. Dynasore or its derivative would be suitable candidates as potent anti-cancer drugs. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2009.10.105

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  • REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells 査読

    Jie Chen, Masami Watanabe, Peng Huang, Masakiyo Sakaguchi, Kazuhiko Ochiai, Yasutomo Nasu, Mamoru Ouchida, Nam-Ho Huh, Kenji Shimizu, Yuji Kashiwakura, Haruki Kaku, Hiromi Kumon

    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE   24 ( 6 )   789 - 794   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3. a member of the Dkk gene family, is a tumor suppressor in a broad range of cancers. REIC/Dkk-3 transfected stable clones of mouse prostate cancer RM9 cells (RM9-REIC) and the empty vector-transfected control clone cells (RM9-EV) were established. Clones were used to evaluate the anti-cancer effects and a proteomics analysis of REIC/Dkk-3 continuous expression was performed. The RM9-REIC cells show a feeble appearance and the cell membrane shows irregular buds known as blebs. In vitro cell proliferation was significantly suppressed in RM9-REIC clones in comparison to the control. The apoptosis assay was done under standard culture conditions and RM9-REIC showed a higher incidence of apoptosis. The RM9-EV and RM9-REIC cells were orthotopically implanted into a C57BL/6 mouse prostate. After 2 weeks, the tumor growth was significantly inhibited in RM9-REIC cells in comparison to the control. Two-dimensional gel electrophoresis was used to examine the modification of protein expression by the gene transfection. The analysis with mass spectrometry disclosed that expression of peroxiredoxin-l, GST-P1. transgelin-2, MRP-L12, ARD, GRP78 and Sorcin were increased and eEF1A-1 and cyclophilin-40 protein were decreased in RM9-REIC cells. Therefore, REIC/Dkk-3 stable transfectants show a reduction of malignancy in mouse prostate cancer RM9 cells in vitro and in vivo. The result of the proteomics analysis might provide important clues to clarify the anti-cancer molecular mechanism of REIC/Dkk-3 gene transfer.

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  • Therapeutic effects of gelatin matrix-embedded IL-12 gene-modified macrophages in a mouse model of residual prostate cancer 査読

    K. Tabata, M. Watanabe, K. Naruishi, K. Edamura, T. Satoh, G. Yang, E. Abdel Fattah, J. Wang, A. Goltsov, D. Floryk, S. D. Soni, D. Kadmon, T. C. Thompson

    PROSTATE CANCER AND PROSTATIC DISEASES   12 ( 3 )   301 - 309   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We evaluated the potential use of intraoperative gelatin matrix hemostatic sealant (GMHS; FloSeal; Baxter Healthcare) embedded with macrophages (M phi) transduced with murine interleukin (IL)-12 recombinant adenoviral vector (G/M phi/AdmIL-12) for prevention of recurrence of prostate cancer following radical prostatectomy. Application of G/M phi/AdmIL-12 resulted in significant suppression of tumor growth and spontaneous lung metastases, a statistically significant survival advantage of the G/M phi/AdmIL-12-treated animals, more efficient trafficking of M phi to lymph nodes draining from the prostate and generation of systemic natural killer cell activity and tumor-specific cytolytic T lymphocyte responses compared to the controls in a preclinical mouse model of residual prostate cancer. Our data recommend this treatment as a novel adjuvant for prevention of local recurrence of prostate cancer following radical prostatectomy. Prostate Cancer and Prostatic Diseases (2009) 12, 301-309; doi: 10.1038/pcan.2008.57; published online 23 December 2008

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  • Functional Analysis of Secreted Caveolin-1 in Mouse Models of Prostate Cancer Progression 査読

    Masami Watanabe, Guang Yang, Guangwen Cao, Salahaldin A. Tahir, Koji Naruishi, Ken-ichi Tabata, Elmoataz Abdel Fattah, Kartik Rajagopalan, Terry L. Timme, Sanghee Park, Shinji Kurosaka, Kohei Edamura, Ryuta Tanimoto, Francesco J. Demayo, Alexei A. Goltsov, Timothy C. Thompson

    MOLECULAR CANCER RESEARCH   7 ( 9 )   1446 - 1455   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Previously, we reported that caveolin-1 (cav-1) is overexpressed in metastatic prostate cancer and that virulent prostate cancer cells secrete biologically active cav-1. We also showed that cav-1 expression leads to prosurvival activities through maintenance of activated Akt and that cav-1 is taken up by other cav-1-negative tumor cells and/or endothelial cells, leading to stimulation of angiogenic activities through PI-3-K-Akt-eNOS signaling. To analyze the functional consequences of cav-1 overexpression on the development and progression of prostate cancer in vivo, we generated PBcav-1 transgenic mice. Adult male PBcav-1 mice showed significantly increased prostatic wet weight and higher incidence of epithelial hyperplasia compared with nontransgenic littermates. Increased immunostaining for cav-1, proliferative cell nuclear antigen, P-Akt, and reduced nuclear p27(KiP1) staining occurred in PBcav-1 hyperplastic prostatic lesions. PBcav-1 mice showed increased resistance to castration-induced prostatic regression and elevated serum cav-1 levels compared with nontransgenic littermates. Intraprostatic injection of androgen-sensitive, cav-1-secreting RM-9 mouse prostate cancer cells resulted in tumors that were larger in PBcav-1 mice than in nontransgenic littermates (P = 0.04). Tall vein inoculation of RM-9 cells produced significantly more experimental lung metastases in PBcav-1 males than in nontransgenic male littermates (P = 0.001), and in cav-1(+/+) mice than in cav-1(-/-) mice (P = 0.041). Combination treatment with surgical castration and systemic cav-1 antibody dramatically reduced the number of experimental metastases. These experimental data suggest a causal association of secreted cav-1 and prostate cancer growth and progression. (Mol Cancer Res 2009;7(9):1446-55)

    DOI: 10.1158/1541-7786.MCR-09-0071

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  • Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7 査読

    Masakiyo Sakaguchi, Ken Kataoka, Fernando Abarzua, Ryuta Tanimoto, Masami Watanabe, Hitoshi Murata, Swe Swe Than, Kaoru Kurose, Yuji Kashiwakura, Kazuhiko Ochiai, Yasutomo Nasu, Hiromi Kumon, Nam-ho Huh

    JOURNAL OF BIOLOGICAL CHEMISTRY   284 ( 21 )   14236 - 14244   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    We previously showed that the tumor suppressor gene REIC/Dkk-3, when overexpressed by an adenovirus (Ad-REIC), exhibited a dramatic therapeutic effect on human cancers through a mechanism triggered by endoplasmic reticulum stress. Adenovirus vectors show no target cell specificity and thus may elicit unfavorable side effects through infection of normal cells even upon intra-tumoral injection. In this study, we examined possible effects of Ad-REIC on normal cells. We found that infection of normal human fibroblasts (NHF) did not cause apoptosis but induced production of interleukin (IL)-7. The induction was triggered by endoplasmic reticulum stress and mediated through IRE1 alpha, ASK1, p38, and IRF-1. When Ad-REIC-infected NHF were transplanted in a mixture with untreated human prostate cancer cells, the growth of the cancer cells was significantly suppressed. Injection of an IL-7 antibody partially abrogated the suppressive effect of Ad-REIC-infected NHF. These results indicate that Ad-REIC has another arm against human cancer, an indirect host-mediated effect because of overproduction of IL-7 by mis-targeted NHF, in addition to its direct effect on cancer cells.

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  • Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression 査読

    Masami Watanabe, Yuji Kashiwakura, Peng Huang, Kazuhiko Ochiai, Junichiro Futami, Shun-Ai Li, Munenori Takaoka, Yasutomo Nasu, Masakiyo Sakaguchi, Nam-Ho Huh, Hiromi Kumon

    INTERNATIONAL JOURNAL OF ONCOLOGY   34 ( 3 )   657 - 663   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The REIC/Dkk-3 gene has been reported to be a tumor suppressor and the expression is significantly down-regulated in a broad range of cancer cell types. The protein is secretory, but the physiological function remains unclear. This study demonstrated that recombinant REIC/Dkk-3 protein induced the differentiation of human CD14(+) monocytes into a novel cell type ((REIC/Dkx-3)Mo). (REIC/Dkk-3)Mo resembles immature dendritic cells generated with IL-4 and GM-CSF. Both these cell populations exhibit similar proportions of CD11c(+), CD40(+), CD86(+) and HLA-DR(+) cells and endocytic capacity, but (REIC/Dkk-3)Mo is negative for CD1a antigen. An analysis of the signal transducers and activators of transcription (STAT) pathways revealed that REIC/Dkk-3 induces phosphorylation of STAT 1 and STAT 3. Furthermore, intratumoral administration of REIC/Dkk-3 protein significantly suppressed tumor growth with CD11c(+) and CD8(+) (dendritic and killer T cell marker, respectively) cell accumulation and enhanced anticancer cytolytic activity of splenocytes. These data indicated a cytokine-like role of REIC/Dkk-3 protein in monocyte differentiation that might be exploited therapeutically.

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  • REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer 査読

    K. Kawasaki, M. Watanabe, M. Sakaguchi, Y. Ogasawara, K. Ochiai, Y. Nasu, H. Doihara, Y. Kashiwakura, N-h Huh, H. Kumon, H. Date

    CANCER GENE THERAPY   16 ( 1 )   65 - 72   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    The overexpression of reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in human prostatic and testicular cancer cells. The aim of this study is to examine the potential of REIC/Dkk-3 as a therapeutic target against breast cancer. First, the in vitro apoptotic effect of Ad-REIC treatment was investigated in breast cancer cell lines and the adenovirus-mediated overexpression of REIC/Dkk-3 was thus found to lead to apoptotic cell death in a c-Jun-NH(2)-kinase (JNK) phosphorylaion-dependent manner. Moreover, an in vivo apoptotic effect and MCF/Wt tumor growth inhibition were observed in the mouse model after intratumoral Ad-REIC injection. As multidrug resistance (MDR) is a major problem in the chemotherapy of progressive breast cancer, the in vitro effects of Ad-REIC treatment were investigated in terms of the sensitivity of multidrug-resistant MCF7/ADR cells to doxorubicin and of the P-glycoprotein expression. Ad-REIC treatment in MCF7/ADR cells also downregulated P-glycoprotein expresssion through JNK activation, and sensitized its drug resistance against doxorubicin. Therefore, not only apoptosis induction but also the reversal of anticancer drug resistance was achieved using Ad-REIC. We suggest that REIC/Dkk-3 is a novel target for breast cancer treatment and that Ad-REIC might be an attractive agent against drug-resistant cancer in combination with conventional antineoplastic agents.

    DOI: 10.1038/cgt.2008.58

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  • Dynamin 2 is required for actin assembly in phagocytosis in Sertoli cells 査読

    Atsushi Otsuka, Tadashi Abe, Masami Watanabe, Hitoshi Yagisawa, Kohji Takei, Hiroshi Yamada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   378 ( 3 )   478 - 482   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Dynamin 2 has been reported to be implicated in phagocytosis. However, the mode of action of dynamin is Poorly understood. In this Study, we examined whether dynamin 2 participates in actin assembly during phagocytosis in Sertoli cells. In the presence of dynasore, a dynamin inhibitor, phagocytosis was reduced by 60-70% in Sertoli cells and macrophages. Scanning electron microscopy revealed that Sertoli cells treated with dynasore were unable to form phagocytic cups. In addition, dysfunction of dynamin 2 reduced both actin polymerization and recruitment of actin and dynamin 2 to phosphatidylinositol (4,5) bisphosphate [ PI(4,5)P(2)]-containing liposomes. The formation of dynamin 2-positive ruffles of Sertoli cells was decreased by 60-70% by sequestering PI(4,5)P2 either by expression of PH domain of PLC delta or treatment with neomycin. These results strongly Suggest that dynamin 2 is involved in actin dynamics and the formation of dynamin 2-positive ruffles during phagocytosis. (C) 2008 Elsevier Inc. All rights reserved.

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  • A comparison of proteomic profiles changes during 17β-estradiol treatment in human prostate cancer PC-3 cell line 査読

    Jie Chen, Peng Huang, Haruki Kaku, Kai Zhang, Masami Watanabe, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

    Cancer Genomics and Proteomics   6 ( 6 )   331 - 335   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Institute of Anticancer Research  

    Human telomerase reverse transcriptase (hTERT) is overexpressed in prostate cancer. Estrogen plays a central role in the development of prostate cancer. hTERT activity has been shown to be increased after estrogen treatment. Although significant efforts have been made to understand the role of estrogen, the telomerase connection with estrogen is poorly understood. In this report, we describe a proteomics approach for investigating the global changes in protein expression in estrogen-treated human prostate cancer PC-3 cells. PC-3 cells were seeded in medium and then treated with estrogen
    the protein extract from these cells was used for two-dimensional (2D) gel electrophoresis. The protein spots were subjected to comparative analysis by liquid chromatography/mass spectrometry (LC/MS). We observed that the expression of 17 proteins, including stress-induced phosphoprotein 1 and lamin-A/C was down-regulated, and that the expression of proteins such as subunit a of T-complex protein 1, tubulin alpha-1B, and other 13 proteins was up-regulated. These proteins may have been closely associated with estrogen-induced hTERT activity. The expression level of these proteins could be a useful parameter for evaluating the estrogen-induced hTERT activity in clinical specimens of human prostate cancer.

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  • Dynamin 2 Cooperates with Amphiphysin 1 in Phagocytosis in Sertoli Cells 査読

    Akira Nakanishi, Tadashi Abe, Masami Watanabe, Kohji Takei, Hiroshi Yamada

    ACTA MEDICA OKAYAMA   62 ( 6 )   385 - 391   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Testicular Sertoli cells highly express dynamin 2 and amphiphysin 1. Here we demonstrate that dynamin 2 is implicated in phosphatidylserine (PS)-dependent phagocytosis in Sertoli cells. Immunofluorescence and dual-live imaging revealed that dynamin 2 and amphiphysin 1 accumulate simultaneously at ruffles. These proteins are specifically bound in vitro. Over-expression of dominant negative dynamin 2 (K44A) inhibits liposome-uptake and leads to the mis-localization of amphiphysin 1. Thus, the cooperative function of dynamin 2 and amphiphysin 1 in PS-dependent phagocytosis is strongly suggested.

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  • Down-regulation of Inhibition of Differentiation-1 via Activation of Activating Transcription Factor 3 and Smad Regulates REIC/Dickkopf-3-Induced Apoptosis 査読

    Yuji Kashiwakura, Kazuhiko Ochiai, Masami Watanabe, Fernando Abarzua, Masakiyo Sakaguchi, Munenori Takaoka, Ryuta Tanimoto, Yasutomo Nasu, Nam-ho Hub, Hiromi Kumon

    CANCER RESEARCH   68 ( 20 )   8333 - 8341   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, has been investigated in gene therapy studies. Our previous study suggested that REIC/Dkk-3-induced apoptosis mainly resulted from phosphorylation of c-Jun-NH2 kinase (JNK) in prostate cancer cells. However, the precise mechanisms, especially the molecular mechanisms regulating JNK phosphorylation, remain unclear. In this study, we investigated the mechanisms participating in JNK phosphorylation in the context of a refractory cancer disease, malignant mesothelioma (MM). Adenovirus-mediated overexpression of REIC/Dkk-3 induced apoptosis mainly through JNK activation in immortalized MM cells (211H cells). Interestingly, transcriptional down-regulation of inhibition of differentiation-1 (Id-1) was detected in REIC/Dkk-3-overexpressed 211H cells. Moreover, restoration of Id-1 expression antagonized REIC/Dkk-3-induced JNK phosphorylation and apoptosis. Mutagenesis experiments with the 2.1-kb human Id-1 promoter revealed that activating transcription factor 3 (ATF3) and Smad interaction, with their respective binding motifs, was essential for REIC/Dkk-3-mediated suppression of Id-1 promoter activity. ATF3 activation was probably induced by endoplasmic reticulum stress. Finally, we showed strong antitumor effects from REIC/Dkk-3 gene transfer into the pleural cavity in an orthotopic MM mouse model. Relative to control tumor tissue, REIC/Dkk-3-treated tumor tissue showed down-regulated expression of Id-1 mRNA, enhanced expression of phosphorylated JNK, and an increased number of apoptotic cells. In summary, we first showed that both ATF3 and Smad were crucially and synergistically involved in down-regulation of Id-1, which regulated JNK phosphorylation in REIC/Dkk-3-induced apoptosis. Thus, gene therapy with REIC/Dkk-3 may be a promising therapeutic tool for MM. [Cancer Res 2008;68(20):8333-41]

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  • An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis 査読

    Fernando Abarzua, Yuji Kashiwakura, Munenori Takaoka, Masami Watanabe, Kazuhiko Ochiai, Masakiyo Sakaguchi, Takao Iwawaki, Ryuta Tanimoto, Yasutomo Nasu, Nam-ho Huh, Hiromi Kumon

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   375 ( 4 )   614 - 618   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 ((1-78) REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated (1-78)REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy. (C) 2008 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2008.08.079

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  • Direct and distant antitumor effects of a telomerase-selective oncolytic adenoviral agent, OBP-301, in a mouse prostate cancer model 査読

    P. Huang, M. Watanabe, H. Kaku, Y. Kashiwakura, J. Chen, T. Saika, Y. Nasu, T. Fujiwara, Y. Urata, H. Kumon

    CANCER GENE THERAPY   15 ( 5 )   315 - 322   2008年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We previously constructed OBP-301 ( Telomelysin, a telomerase-specific replication-competent adenovirus with human telomerase reverse transcriptase ( hTERT) promoter), which showed a strong anticancer effect by inducing cell lysis of human non-small cell lung cancer and colorectal cancer cells. To investigate the utility of OBP-301 for prostate cancer treatment, we herein evaluate the cell killing and antitumor effects. First, in vitro hTERT-specific adenovirus transduction in human prostate cancer cells ( LNCaP, PC3, DU145) was confirmed using OBP-401 ( Telomelysin-green fluorescent protein ( GFP)). There was no detectable GFP transduction in the human prostate normal cells ( PrEC, PrSC). Consistently, the cell-killing effect of OBP-301 was observed only in the cancer cells. Second, using an in vivo subcutaneous LNCaP tumor model in nude mice, we demonstrated that three intratumoral OBP-301 injections ( 10(7) PFU per tumor x 3 days) were sufficient to eradicate the detectable LNCaP prostate tumor. We also demonstrated that the ispilateral treatment with OBP-301 significantly suppressed contralateral LNCaP tumor growth in both sides of the tumor model. Histological and immunohistochemical analyses revealed diffuse oncolytic degeneration and adenoviral E1A protein expression in both sides of the tumors. Therefore, in situ OBP-301 administration could be a promising therapeutic strategy against prostate cancer and its metastatic lesions.

    DOI: 10.1038/cgt.2008.3

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  • Adenovirus-mediated REIC/DKK-3 gene transfer prevented mesothelioma tumor progressions in orthotopic mice model 査読

    Kashiwakura Yuji, Watanabe Masami, Abarzua Fernando, Sakaguchi Masakiyo, Takaoka Munenori, Tanimoto Ryuta, Nasu Yasutomo, Huh Nam-ho, Kumon Hiromi

    JOURNAL OF GENE MEDICINE   10 ( 4 )   469 - 470   2008年4月

  • Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer 査読

    Salahaldin A. Tahir, Guang Yang, Alexei A. Goltsov, Masami Watanabe, Ken-ichi Tabata, Josephine Addai, El Moataz Abdel Fattah, Dov Kadmon, Timothy C. Thompson

    CANCER RESEARCH   68 ( 3 )   731 - 739   2008年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Caveolin, a major structural component of specialized plasma membrane invaginations (caveolae) that participate in diverse cellular activities, has been implicated in the pathogenesis of several human diseases, including cancer. We showed in earlier studies that caveolin-1 (cav-1) is consistently and strongly overexpressed in metastatic prostate cancer and is secreted in a biologically active form by virulent prostate cancer cells. Using both in vitro and in vivo model systems, we now present evidence supporting a proangiogenic role for cav-1 in prostate cancer development and progression. Recombinant cav-1 (rcav-1) was taken up by cav-1(-/-) endothelial cells through either a lipid raft/caveolae- or clathrin-dependent mechanism, leading to specific angiogenic activities (tubule formation, cell migration, and nitric oxide production) that were mediated by rcav-1 stimulation of the PI3K-Akt-eNOS signaling module. Pathologic angiogenesis induced by cav-1 in prostate cancer-bearing mice correlated with an increased frequency, number, and size of lung metastases. We propose that in addition to its antiapoptotic role, cav-1 secreted by prostate cancer cells functions critically as a proangiogenic factor in metastatic progression of this tumor. These new insights into cav-1 function in prostate cancer may provide a base for the design of clinically applicable therapeutic strategies.

    DOI: 10.1158/0008-5472.CAN-07-2668

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  • Amphiphysin 1 is important for actin polymerization During phagocytosis 査読

    Hiroshi Yamada, Emiko Ohashi, Tadashi Abe, Norihiro Kusumi, Shun-AI Li, Yumi Yoshida, Masami Watanabe, Kazuhito Tomizawa, Yuji Kashiwakura, Hiromi Kumon, Hideki Matsui, Kohji Takei

    MOLECULAR BIOLOGY OF THE CELL   18 ( 11 )   4669 - 4680   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Amphiphysin 1 is involved in clathrin-mediated endocytosis. In this study, we demonstrate that amphiphysin 1 is essential for cellular phagocytosis and that it is critical for actin polymerization. Phagocytosis in Sertoli cells was induced by stimulating phosphatidylserine receptors. This stimulation led to the formation of actin-rich structures, including ruffles, phagocytic cups, and phagosomes, all of which showed an accumulation of amphiphysin 1. Knocking out amphiphysin 1 by RNA interference in the cells resulted in the reduction of ruffle formation, actin polymerization, and phagocytosis. Phagocytosis was also drastically decreased in amph 1(-/-) Sertoli cells. In addition, phosphatidylinositol-4,5-bisphosphate-induced actin polymerization was decreased in the knockout testis cytosol. The addition of recombinant amphiphysin 1 to the cytosol restored the polymerization process. Ruffle formation in small interfering RNA-treated cells was recovered by the expression of constitutively active Rac1, suggesting that amphiphysin 1 functions upstream of the protein. These findings support that amphiphysin 1 is important in the regulation of actin dynamics and that it is required for phagocytosis.

    DOI: 10.1091/mbc.E07-04-0296

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  • Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model 査読

    K. Edamura, Y. Nasu, M. Takaishi, T. Kobayashi, F. Abarzua, M. Sakaguchi, Y. Kashiwakura, S. Ebara, T. Saika, M. Watanabe, N-H Huh, H. Kumon

    CANCER GENE THERAPY   14 ( 9 )   765 - 772   2007年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We had previously reported that REIC/Dkk-3, a member of the Dickkopf ( Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene ( Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.

    DOI: 10.1038/sj.cgt.7701071

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  • Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3 査読

    Fernando Abarzua, Masakiyo Sakaguchi, Ryuta Tanimoto, Hiroyuki Sonegawa, Dai-Wei L, Kohei Edamura, Tomoko Kobayashi, Masami Watanabe, Yuji Kashiwakura, Haruki Kaku, Takashi Saika, Keiichiro Nakamura, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE   20 ( 1 )   37 - 43   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    We recently showed that overexpression of REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in a tumor cell-specific manner. The aim of the present study was to determine the mechanisms underlying the selective induction of apoptosis. At first, we found a mouse renal carcinoma cell line, RENCA, to be extremely sensitive to an adenovirus carrying REIC/Dkk-3 (Ad-REIC), and we showed that activation of c-Jun N-terminal kinase (JNK) was a critical step in cell death, i.e. a process similar to that in human prostate and testicular cancer observed in our previous studies. Among the proteins interfering with the activation of JNK, heat shock protein (Hsp)70/72 was reduced in expression in RENCA cells compared with that in NIH3T3 cells. An Hsp70/72 inducer protected RENCA cells from Ad-REIC-induced apoptosis, while an Hsp70/72 inhibitor sensitized NIH3T3 cells for apoptosis induction. These results indicate that functionally active Hsp70/72 is a key factor in tumor cell-specific induction of apoptotic cell death and that analyses of the expression levels of Hsp70/72 may be essential in determining the significance of Ad-REIC-based gene therapy against human cancer.

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  • テロメラーゼ特異的複製:前立腺癌に対する選択的ウイルス療法(Telomerase-Specific Replication: Selective Virotherapy for Prostate Cancer) 査読

    黄 鵬, 渡部 昌実, 陳 潔, 賀来 春紀, 那須 保友, 雑賀 隆史, 藤原 俊義, 浦田 泰生, 公文 裕巳

    日本泌尿器科学会雑誌   98 ( 2 )   458 - 458   2007年2月

  • Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer 査読

    T. Fujita, T. L. Timme, K. Tabata, K. Naruishi, N. Kusaka, M. Watanabe, E. Abdelfattah, J. X. Zhu, C. Ren, C. Ren, G. Yang, A. Goltsov, H. Wang, M. T. Vlachaki, B. S. Teh, E. B. Butler, T. C. Thompson

    GENE THERAPY   14 ( 3 )   227 - 236   2007年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We investigated the potential benefits of combining adenoviral vector mediated in situ interleukin-12 (AdmIL-12) gene therapy with radiation therapy (XRT) to enhance therapeutic efficacy. In a metastatic mouse prostate cancer cell line, 1782 BMA, AdmIL-12+XRT demonstrated enhanced therapeutic activities in vitro as determined by clonogenic survival, apoptosis, and mIL-12 levels. At the molecular level, increased expression of tumor necrosis factor-alpha mRNA was specific for the combined therapy. In a subcutaneous 178-2 BMA in vivo model, the combination of AdmIL-12+XRT produced statistically significant tumor growth suppression compared to control vector Ad beta gal, Ad beta gal XRT, or AdmIL-12 as monotherapy. In addition, significant prolongation of survival was demonstrated for the combination of AdmIL-12+XRT. The combination of AdmIL-12+XRT significantly suppressed both spontaneous and pre-established lung metastases, and led to a prolonged elevation of serum IL-12 and significantly increased natural killer (NK) activities. Importantly, in vivo depletion of NK cells resulted in significant attenuation of the antimetastatic activities of AdmIL-12 alone or AdmIL-12+XRT. These combined effects suggest that AdIL-12 gene therapy together with radiotherapy may achieve maximal tumor control (both local and systemic) in selected prostate cancer patients via radio-gene therapy induced local cytotoxicity and local and systemic antitumor immunity.

    DOI: 10.1038/sj.gt.3302788

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  • Implication of amphiphysin 1 and dynamin 2 in tubulobulbar complex formation and spermatid release 査読

    Norihiro Kusumi, Masami Watanabe, Hiroshi Yamada, Shun-Ai Li, Yuji Kashiwakura, Takashi Matsukawa, Atsushi Nagai, Yasutomo Nasu, Hiromi Kumon, Kohji Takei

    CELL STRUCTURE AND FUNCTION   32 ( 2 )   101 - 113   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC CELL BIOLOGY  

    Tubulobulbar complexes (TBCs) are composed of several tubular invaginations formed at the plasma membrane of testicular Sertoli cells. TBCs are transiently formed at the contact region with spermatids at spermatogenic stage VII in rat and mouse, and such TBC formation is prerequisite for spermatid release. Since the characteristic structure of TBCs suggests that the molecules implicated in endocytosis could be involved in TBC formation, we here investigated the localization and physiological roles of endocytic proteins, amphiphysin 1 and dynamin 2, at TBCs. We demonstrated by immunofluorescence that the endocytic proteins were concentrated at TBCs, where they colocalized with cytoskeletal proteins, such as actin and vinculin. Immunoelectron microscopy disclosed that both amphiphysin 1 and dynamin 2 were localized on TBC membrane. Next, we histologically examined the testis from amphiphysin 1 deficient {Amph(-/-)} mice. Morphometric analysis revealed that the number of TBCs was significantly reduced in Amph(-/-). The ratio of stage VIII seminiferous tubules was increased, and the ratio of stage IX was conversely decreased in Amph(-/-). Moreover, unreleased spermatids in stage VIII seminiferous tubules were increased in Amph(-/-), indicating that spermatid release and the following transition from stage VIII to IX was prolonged in Amph(-/-) mice. These results suggest that amphiphysin 1 and dynamin 2 are involved in TBC formation and spermatid release at Sertoli cells.

    DOI: 10.1247/csf.07024

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  • Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer 査読

    K. Naruishi, T. L. Timme, N. Kusaka, T. Fujita, G. Yang, A. Goltsov, T. Satoh, X. Ji, W. Tian, E. Abdelfattah, T. Men, M. Watanabe, K. Tabata, T. C. Thompson

    CANCER GENE THERAPY   13 ( 7 )   658 - 663   2006年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We previously identified a novel p53 target gene, RTVP-1, that possesses unique cytotoxic and immunostimulatory activities which make it potentially useful for cancer gene therapy. To test the therapeutic potential of RTVP-1 in a gene- modified tumor cell-based vaccine model, we used an adenoviral vector capable of efficient transduction and expression of RTVP-1 (AdRTVP-1), together with a highly metastatic mouse prostate cancer cell line (178-2 BMA). A vaccine was prepared with 178-2 BMA cells transduced with AdRTVP-1 or a control adenoviral vector expressing beta-galactosidase (Ad beta gal). After irradiation of the cells, syngeneic 129/Sv mice were vaccinated three times at weekly intervals. After 3 weeks, they were challenged with orthotopic 178-2 BMA cells. After 21 days, fewer than 60% of the RTVP-1-cell-vaccinated mice developed tumors compared to 100% of the control mice. The RTVP-1-cell vaccine significantly reduced primary tumor wet weight compared with control Ad beta gal-cell vaccine (P < 0.0001 at 7 and 14 days). Experimental metastasis to lung was also significantly reduced (P = 0.0377), and survival significantly increased (P = 0.0002). In addition, significantly increased NK and CTL activities were demonstrated in the AdRTVP-1-cell-vaccinated mice. These findings indicate that RTVP-1 gene-modified cell-based vaccines may be useful in the prevention of recurrent prostate cancer.

    DOI: 10.1038/sj.cgt.7700919

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  • Extensive biopsy using a combined transperineal and transrectal approach to improve prostate cancer detection 査読

    M Watanabe, T Hayashi, T Tsushima, S Irie, T Kaneshige, H Kumon

    INTERNATIONAL JOURNAL OF UROLOGY   12 ( 11 )   959 - 963   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Purpose: Previous studies have indicated that 6-core transrectal prostate biopsy misses a considerable number of cancers. We performed an extensive biopsy protocol of 12-core sampling using both transperineal and transrectal approaches to determine the impact on the cancer detection rate.
    Materials and methods: We prospectively evaluated 402 men who underwent 6-core transperineal and 6-core transrectal biopsies simultaneously due to abnormal digital rectal examination (DRE) and/or elevated prostate-specic antigen (PSA) levels of 4.0 ng/mL or greater. Using the transperineal approach we obtained four cores from the bilateral peripheral zone targeting the lateral and parasagittal areas and two cores from the bilateral transition zone. The following transrectal biopsy was performed traditionally. We compared cancer detection rate between the extended 12-core procedure and conventional 6-core transperineal and transrectal groups in terms of total PSA and DRE ndings.
    Results: Using the extensive combined method, prostate cancer was detected in 195 cases (48.5%) and the detection rate signicantly increased 7.2% and 8.5% compared to the transperineal and transrectal groups, respectively. According to PSA levels and DRE ndings, the cancer detection rate by the combined method was signicantly improved in patients with PSA levels of 4-10 ng/mL and negative DRE: 10.3% and 11.6% compared to the transperineal and transrectal groups, respectively.
    Conclusions: The extensive 12-core method signicantly improved the overall cancer detection rate and was especially efcient for men with PSA levels of 4-10 ng/mL accompanied by a negative DRE nding.

    DOI: 10.1111/j.1442-2042.2005.01186.x

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  • Minimal invasiveness and effectivity of subinguinal microscopic varicocelectomy: a comparative study with retroperitoneal high and laparoscopic approaches 査読

    M Watanabe, A Nagai, N Kusumi, H Tsuboi, Y Nasu, H Kumon

    INTERNATIONAL JOURNAL OF UROLOGY   12 ( 10 )   892 - 898   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Aim: The standard management of varicocele repair is the subject of ongoing controversy. We retrospectively evaluated three surgical methods of varicocele treatment to determine the minimally invasive and most effective procedure.
    Methods: We performed 144 varicocelectomies on infertile patients with left clinical varicocele. Of the patients, 50 were treated with retroperitoneal high ligation under lumbar anesthesia, 33 with laparoscopic ligation under general anesthesia, and 61 with subinguinal microscopic ligation under local anesthesia. Operative time, hospital days, and clinical outcomes were compared between these techniques.
    Results: The operating time and hospitalization period required for subinguinal microscopic ligation was signicantly shorter compared to those for the other procedures. All patients treated with subinguinal microscopic ligation could achieve normal activity as soon as they returned to their rooms. Postoperative complications were observed in ve (10.0%) cases treated with high ligation and three (9.1%) laparoscopic cases, but were not observed after the subinguinal procedure. There were six cases (12.0%) of recurrence in the high ligation group and six (6.1%) in the laparoscopic group, but none in the subinguinal group. Sperm density was signicantly improved in all procedures postoperatively, but sperm motility was not improved. The two-year pregnancy rate calculated by the Kaplan-Meier method was 35.8% for high ligation, 40.4% for laparoscopic ligation and 50.9% for subinguinal microscopic ligation, although there were no statistical differences between the three groups.
    Conclusion: We concluded that subinguinal microscopic varicocelectomy could be a minimally invasive procedure compared to the other two techniques and a worthy method for treating male infertility due to clinical varicocele.

    DOI: 10.1111/j.1442-2042.2005.01142.x

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  • Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis 査読

    M Watanabe, Y Kashiwakura, N Kusumi, K Tamayose, Y Nasu, A Nagai, T Shimada, H Daida, H Kumon

    GENE THERAPY   12 ( 14 )   1126 - 1132   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Testicular germ cell-induced autoimmune orchitis is characterized by inflammatory cell infiltration followed by disturbance of spermatogenesis. Experimental autoimmune orchitis (EAO) is an animal model for human immunological male infertility; delayed-type hypersensitivity (DTH) response plays a key role in its induction. Interleukin-10 (IL-10) is a regulatory cytokine that is critical in preventing organ-specific autoimmune inflammation. To determine the effects on EAO of human IL-10 (hIL-10) gene transfer, C3H/He mice immunized by unilateral testicular injury were administered intramuscular ( i.m.) injections of adeno-associated viral (AAV) vector-encoding hIL-10 on the day of immunization. Serum hIL-10 was detected beginning at 1 week postinjection, and peaked at 3 weeks. Histological examinations showed a significantly low incidence of orchitis and disturbance of spermatogenesis in AAV hIL-10-treated mice, and the DTH response to autologous testicular cells was significantly suppressed. Immunohistochemical analysis of IFN-gamma and IL-2, T-cell-associated cytokines, in the spleen and testes revealed significantly fewer cytokine-expressing cells after treatment. We conclude that a single i.m. administration of AAV hIL-10 significantly suppresses EAO and hypospermatogenesis by regulating cell-mediated immunity in the testes.

    DOI: 10.1038/sj.gt.3302463

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  • Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: Long-term maspin expression efficiently suppresses tumor growth 査読

    M Watanabe, Y Nasu, Y Kashiwakura, N Kusumi, K Tamayose, A Nagai, T Sasano, T Shimada, H Daida, H Kumon

    HUMAN GENE THERAPY   16 ( 6 )   699 - 710   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT INC  

    Maspin is a member of the serine protease inhibitors and the maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of prostate cancers. We evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding maspin as a means for in vivo gene therapy for human prostate cancer. TUNEL assay of subcutaneously formed LNCaP or DU145 tumors in nude mice showed that intratumoral AAV-mediated maspin expression significantly upregulated the number of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double staining for maspin protein and apoptosis in LNCaP tumors showed that the percentage of apoptotic cells in AAV-maspin-mediated maspin-expressing cells was significantly high compared with that in AAV-GFP-mediated GFP-expressing cells. Moreover, significantly fewer CD31-positive microvessels were observed in AAV-maspin-treated tumors compared with the control tumors. These therapeutic responses were highly correlated to persistent maspin expression in tumors, confirmed by Western blot analysis until at least day 56 after treatment. Finally, intratumoral delivery of AAV-maspin significantly suppressed growth of LNCaP and DU145 tumors and improved survival of mice. We conclude that AAV-mediated prolonged maspin expression efficiently suppresses human prostate tumor growth in vivo by apoptosis induction and inhibition of angiogenesis.

    DOI: 10.1089/hum.2005.16.699

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  • Varicocele rupture due to sexual intercourse 査読

    Y Nishiyama, A Nagai, Y Nasu, M Watanabe, N Kusumi, K Monden, H Kumon

    INTERNATIONAL JOURNAL OF UROLOGY   12 ( 6 )   585 - 587   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    Varicocele rupture was diagnosed in a 23-year-old man who presented with swelling and pain in the left scrotum after sexual intercourse. Color Doppler ultrasonography revealed blood flowing into the space surrounding the left testis, a hematoma and reflux of blood in the left spermatic vein. Varicocele rupture is a very rare condition and there have been only five reported cases.

    DOI: 10.1111/j.1442-2042.2005.01096.x

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  • Clinical results of one-stage urethroplasty with parameatal foreskin flap for hypospadias 査読

    A Nagai, Y Nasu, M Watanabe, N Kusumi, H Tsuboi, H Kumon

    ACTA MEDICA OKAYAMA   59 ( 2 )   45 - 48   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We investigated the usefulness of one-stage urethroplasty by the parameatal foreskin flap method (OUPF procedure), which is useful for repairing all types of hypospadias. Between June 1992 and March 2001, the OUPF procedure was performed on 18 patients with hypospadias: 10 patients with distal and 8 with proximal hypospadias. The follow-up periods ranged from 33-75 months, with an average of 52 months. The duration of surgery, the catheter indwelling period, and the postoperative complications of each patient were analyzed. The median age of the patients at the time of surgery was 3 years and 8 months. The length of surgery for OUPF II ranged from 150-230 min (average 186 min), and from 190-365 min (average 267 min) for OUPF IV. Postoperative complications were confirmed in 3 of the 18 patients (16.6%). Two patients had fistulas, and one had a meatal regression. The fistulas were successfully closed by the simple multilayered closure method. After adopting DuoDerm dressings instead of elastic bandages for protection of the wound, no fistulization occurred. DuoDerm dressings are useful in the healing of wounds without complications. To date, the longest follow-up period has been 75 months, and during that time there have been no late complications such as urethral stenosis or penile curvature. OUPF is a useful method in the treatment of hypospadias with a low incidence of early and late complications.

    DOI: 10.18926/AMO/31964

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  • Analysis of human ejaculation using color Doppler ultrasonography: A comparison between antegrade and retrograde ejaculation 査読

    A Nagai, M Watanabe, Y Nasu, H Iguchi, N Kusumi, H Kumon

    UROLOGY   65 ( 2 )   365 - 368   2005年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Objectives. To observe the phenomenon of human ejaculation dynamically using color Doppler ultrasonography.
    Methods. Human ejaculation was observed using transrectal color Doppler ultrasonography in a healthy man and a patient with retrograde ejaculation. Ejaculation was induced manually with audiovisual sexual stimulation. The ejaculatory phenomenon was analyzed and compared with that of retrograde ejaculation.
    Results. In the healthy man, the prostatic urethra flattened slightly and the bladder neck contracted just before expulsion. The ejaculatory stream spurted from the seminal vesicles to the bulbous urethra through the ejaculatory duct. In the patient with retrograde ejaculation, the ejaculatory stream from the seminal vesicles and inframontanal and distal prostatic urethras distended into a globular-shaped sac filled with semen. No seminal flow toward the bulbous urethra occurred. The semen remaining in the prostatic urethra began flowing slowly into the bladder.
    Conclusions. Differences between antegrade and retrograde ejaculation can be clearly detected by color Doppler ultrasonography, providing a noninvasive method to diagnose ejaculatory disorders. UROLOGY 65: 365-368, 2005. (C) 2005 Elsevier Inc.

    DOI: 10.1016/j.urology.2004.09.016

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  • Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection 査読

    Y Kashiwakura, K Tamayose, K Iwabuchi, Y Hirai, T Shimada, K Matsumoto, T Nakamura, M Watanabe, K Oshimi, H Daida

    JOURNAL OF VIROLOGY   79 ( 1 )   609 - 614   2005年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    After the first attachment of virus to the cell surface through a primary receptor, efficient entry of virus requires the presence of a coreceptor. For adeno-associated virus type 2 (AAV2) infection, heparan sulfate proteoglycan is supposed as the primary receptor, and alphavbeta5 integrin and FGFR1 are reported to act as coreceptors. In this study, we were able to demonstrate that hepatocyte growth factor receptor, e-Met, is also a coreceptor for AAV2 infection. AAV2-mediated transgene analyses revealed that c-Met expression significantly up-regulated transgene expression without increasing AAV2 cell binding. Moreover, a viral overlay assay elucidated the physical interaction between AAV2 and the beta subunit of c-Met. These data suggest that c-Met plays the role of coreceptor for AAV2 infection by facilitating AAV2 internalization into the cytoplasm.

    DOI: 10.1128/JVI.79.1.609-614.2005

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  • Cytosolic Ca2+ responses to sub-picomolar and nanomolar PACAP in pancreatic beta-cells are mediated by VPAC2 and PAC1 receptors 査読

    H Yamada, M Watanabe, T Yada

    REGULATORY PEPTIDES   123 ( 1-3 )   147 - 153   2004年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates glucose-induced insulin release and increases cytosolic Ca2+ concentration ([Ca2+](i)) in islet beta-cells in a concentration-dependent manner with two peaks at 10(-13) and 10(-9) M. PAC1 receptor (PAC1-R) and VPAC2 receptor (VPAC2-R) are expressed in pancreatic beta-cells and thought to be involved in insulin release. We aimed to determine the receptor types involved in the [Ca-2](i) responses to 10(-13) and 10(-9) M PACAP. We measured [Ca2+](i) in beta-cells and examined comparative effects of PAC1-R-selective agonist maxadilan, its antagonist M65, VPAC2-R-selective agonist Ro25-1553, and native ligands of PACAP and VIP. In the presence of 8.3 mM glucose, maxadilan, Ro25-1553, PACAP, and VIP at 10(-13) and 10(-9) M all increased [Ca2+](i). PACAP and maxadilan elicited greater effects at 10(-9) M than at 10(-13) M both in the incidence and amplitude of [Ca2+](i) responses. For VIP and Ro25-1553, in contrast, the effects at 10(-9) and 10(-13) M were comparable. Furthermore, the amplitude of [Ca2+](i) responses to 10(-9) M PACAP, but not 10(-13) M PACAP, was suppressed by M65. The results suggest that VPAC2-R and PAC1-R contribute equally to [Ca2+](i) responses to sub-picomolar concentrations of PACAP, while PAC1-R has greater contribution to [Ca2+](i) responses to nanomolar concentrations of this peptide. (C) 2004 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.regpep.2004.03.020

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  • Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice 査読

    SA Li, M Watanabe, H Yamada, A Nagai, M Kinuta, K Takei

    CELL STRUCTURE AND FUNCTION   29 ( 4 )   91 - 99   2004年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC CELL BIOLOGY  

    Klotho mutant mouse (kl-/-), a mouse model for human aging. exhibits various phenotypes in a wide range of organs including arteriosclerosis, neural degeneration. skin and gonadal atrophy, pulmonary emphysema, calcification of soft tissues, and cognition impairment. Klotho mRNA. however. is expressed only in brain, kidney, reproductive organs, pituitary gland, and parathyroid gland. Therefore it remains to be elucidated how lack of Klotho protein in these limited organs leads to the variery of phenotypes. To shed light on mechanisms by which Klotho protein acts on distant targets, we examined localization of Klotho protein in brain. kidney. and reproductive organs, and analyzed brain and kidney in kl-/- mice searching for changes in target regions in these organs. In brain, Klotho proteins were localized at choroid plexus, where the proteins were dominantly localized at the apical plasma membrane of ependymal cells. In kl-/- brain, reduction of synapses was evident in hippocampus, suggesting a role of Klotho as a humoral factor in cerebrospinal fluid. Klotho proteins in kidney localized at distal renal tubules. Interestingly, in kl-/- mice, type IIa Na/phosphate (Pi) cotransporters, which function at the proximal renal tubules in reabsorption of phosphate ions. were translocated. This suggests that Klotho protein in kidney is implicated in calcium homeostasis which regulates localization of type IIa Na/Pi cotransporters via parathyroid hormone (PTH). Klotho proteins in reproductive organs were expressed only in mature germ cells, although in kl-/- mice germ cell maturation was arrested at earlier stages. Thus, Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation. which may explain why mutation of klotho gene results in a variety of phenotypes.

    DOI: 10.1247/csf.29.91

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  • Dynamin-2 regulates oxidized low-density lipoprotein-induced apoptosis of vascular smooth muscle cell 査読

    Y Kashiwakura, M Watanabe, N Kusumi, K Sumiyoshi, Y Nasu, H Yamada, T Sawamura, H Kumon, K Takei, H Daida

    CIRCULATION   110 ( 21 )   3329 - 3334   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Background-On exposure to oxidized low-density lipoprotein (oxLDL), vascular cells generally undergo apoptosis, which is one of the major pathogenic factors of atherosclerosis. In this study, we examined the role of dynamin ( a crucial GTPase protein in endocytosis) in oxLDL-induced apoptosis of vascular smooth muscle cells (VSMC).
    Methods and Results-After oxLDL stimulation, dynamin-2 colocalized with LOX-1 around the cell surface, as well as oxLDL in the cytoplasm, suggesting that dynamin-2 was involved in scavenger receptor-mediated oxLDL endocytosis. Downregulation of dynamin-2 induced by dynamin-2 dominant negative plasmid (K44A) resulted in a decrease of oxLDL uptake and thereby in a reduction of apoptosis. These data demonstrated that dynamin-2 was involved in oxLDL-induced apoptosis via the oxLDL endocytotic pathway. On the other hand, dynamin-2 wild-type plasmid transfection promoted oxLDL-induced apoptosis without increasing oxLDL uptake. Interestingly, the p53 inhibitor pifithrin-alpha (PFT) significantly reduced apoptosis promoted by wild-type dynamin-2 (78% reduction compared with the PFT[-] condition). These results indicated that dynamin-2 enhanced oxLDL-induced apoptosis of VSMC by participating in the p53 pathway, probably as a signal transducer. Moreover, we demonstrated that, in advanced plaques of apolipoprotein E-/- mice, dynamin-2 expression was often enhanced in apoptotic VSMC, suggesting that dynamin-2 might participate in apoptosis of VSMC even in vivo.
    Conclusions - Our data demonstrated that dynamin-2 at least partially regulated oxLDL-induced apoptosis of VSMC by participating in 2 independent pathways: the oxLDL endocytotic pathway and the p53 pathway. These findings suggest that dynamin-2 may serve as a new research or therapeutic target in vascular disease.

    DOI: 10.1161/01.CIR.0000147828.86593.85

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  • Analysis of retrograde ejaculation using color Doppler ultrasonography before and after transurethral collagen injection 査読

    A Nagai, Y Nasu, M Watanabe, M Tsugawa, H Iguchi, H Kumon

    INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH   16 ( 5 )   456 - 458   2004年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Transurethral bladder neck collagen injection therapy was performed in a patient with retrograde ejaculation. The phenomenon of retrograde ejaculation and its correction after the therapy were clearly demonstrated by color Doppler ultrasonography. To our knowledge this is the first report showing successful observation of retrograde ejaculation using color Doppler ultrasonography.

    DOI: 10.1038/sj.ijir.3901202

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  • Localization of dynamin 2 in rat seminiferous tubules during the spermatogenic cycle 査読

    H Iguchi, M Watanabe, A Kamitani, A Nagai, O Hosoya, K Tsutsui, H Kumon

    ACTA MEDICA OKAYAMA   56 ( 4 )   205 - 209   2002年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Dynamin is a protein essential to endocytosis. Dynamin 2, a dynamin isoform, is expressed most intensely in testicular tissue; however, precise localization has never been studied. Therefore, we investigated the expression of dynamin 2 in rat testicular tissue using immunohistochemical methods, and discuss here the physiological function of this protein. Testicular tissues were obtained from Wistar rats at 10, 21 and 63 days of age. Immunohistochemistrical examination and Western blot analysis were conducted using dynamin 2 specific antibody. Western blot analysis showed that expression in 21- and 63-day-old rats was more intense than that in 10-day-old rats. Dynamin 2 expression was observed using immunohistochemical method in the seminiferous tubules of all rats. In the 63-day-old rats, the expression was intense, especially in spermatids in the earlier maturation stages and in spermatocytes, and was observed in Sertoli cells. However, in spermatids, the expression gradually declined as spermatids matured to spermatozoa. In the 21-day-old rats, the expression was evident in spermatocytes and Sertoli cells, but that in the 10-day-old rats was weak. Intense expression of dynamin 2 during spermatogenesis suggests that this protein plays an important role in this process.

    DOI: 10.18926/AMO/31681

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  • Distribution of dynamins in testis and their possible relation to spermatogenesis 査読

    A Kamitani, H Yamada, M Kinuta, M Watanabe, SA Li, T Matsukawa, M McNiven, H Kumon, K Takei

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   294 ( 2 )   261 - 267   2002年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Dynamin 2 and dynamin 3 are highly expressed in testis. However, their functions in the tissue remain unclear. Considering that dynamin 1, neuron-specific isoform of dynamin, plays a pivotal role in endocytosis, functions of dynamin 2 and dynamin 3 in testis must be essential. Cellular expression and subcellular localization of dynamin 2 and dynamin 3 in testis were investigated. Dynamin 2 and dynainin 3 were highly expressed in germ cells and Sertoli cells, constituents of seminiferous tubules. By immunofluorescence it was revealed that dynamin 2 colocalizes with clathrin both at the plasmamembrane and at Golgi in a cell line of Sertoli cells. Immuno reactivity for dynamin 3, on the other hand, appeared as finer puncta, which did not colocalize with clathrin, suggesting that these two dynamins have distinct functions in Sertoli cells. In the klotho deficient mouse testis, which demonstrates disorder in spermatogenesis, expression of dynamin 2 and dynamin 3 was drastically reduced indicating possible association of these proteins with spermatogenesis. (C) 2002 Elsevier Science (USA). All rights reserved.

    DOI: 10.1016/S0006-291X(02)00470-9

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  • Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture 査読

    H Yamada, M Hayashi, S Uehara, M Kinoshita, A Muroyama, M Watanabe, K Takei, Y Moriyama

    JOURNAL OF NEUROCHEMISTRY   81 ( 3 )   533 - 540   2002年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    5-Hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin synthesis in mammalian pinealocytes. 5-HT is present in organelles distinct from L-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance serotonin N-acetyltransferase activity via the 5-HT2 receptor. However, the mechanism underlying the secretion of 5-HT from pinealocytes is unknown. In this study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat pinealocytes in culture. Omission of Ca2+ from the medium and incubation of pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE-evoked 5-HT release, respectively. Phenylephrine also triggered the Ca2+-dependent release of 5-HT, which was blocked by phentolamine, an alpha antagonist, but not by propranolol, a beta antagonist. Botulinum neurotoxin type E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE-evoked 5-HT release. Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5-HT release. Agents that trigger L-glutamte exocytosis such as acetylcholine did not trigger any Ca2+-dependent 5-HT release. Vice versa neither NE nor phenylephrine caused synaptic-like microvesicle-mediated L-glutamate exocytosis. These results indicated that upon stimulation of a adrenoceptors pinealocytes secrete 5-HT through a Ca-2-dependent exocytotic mechanism, which is distinct from the exocytosis of synaptic-like microvesicles.

    DOI: 10.1046/j.1471-4159.2002.00839.x

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  • Phosphatidylinositol 4,5-bisphosphate stimulates vesicle formation from liposomes by brain cytosol 査読

    M Kinuta, H Yamada, T Abe, M Watanabe, SA Li, A Kamitani, T Yasuda, T Matsukawa, H Kumon, K Takei

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   99 ( 5 )   2842 - 2847   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    As a step toward the elucidation of mechanisms in vesicle budding, a cell-free assay that measures cytosol-induced vesicle generation from liposomes was established. This assay then was used to explore the role of phosphoinositides in vesicle formation. Liposomes incubated with brain cytosol in the presence of ATP and GTP massively generated small vesicles, as assessed both quantitatively and qualitatively by a dynamic light-scattering assay. Both ATP and GTP were required. Vesicle formation was inhibited greatly by the immunodepletion of dynamin 1 from the cytosol, indicating a major contribution of this GTPase in this reaction and suggesting that it mimics endocytic vesicle fission. Increasing the concentration Of L-alpha-phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] but not of L-alpha-phosphatidylinositol 4-monophosphate or L-alpha-phosphatidylinositol in the lipid membranes enhanced vesicle formation. Lipid analysis revealed rapid degradation of PtdIns(4,5)P-2 to L-alpha-phosphatidylinositol during the incubation with the reaction reaching a maximum within 5 sec, whereas vesicle formation proceeded with a longer time course. PtdIns(4,5)P-2 degradation was independent of vesicle formation and occurred also in the presence of guanosine 5'-O-(thiotriphosphate), where few vesicle formations occurred. These results suggest that PtdIns(4,5)P-2 plays a critical role in the early step of vesicle formation, possibly in the recruitment of coats and fission factors to membranes.

    DOI: 10.1073/pnas.261715599

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  • Primary gastric T-cell lymphoma without human T-lymphotropic virus type 1: Report of a case 査読

    M Watanabe, Y Moriyama

    SURGERY TODAY   32 ( 6 )   525 - 530   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER-VERLAG  

    Although primary gastric malignant lymphoma accounts for slightly more than 10% of all lymphomas at extranodular sites, it is relatively rare clinically, representing only 1% of all malignant diseases of the stomach. In addition, most such diseases tend to be B-cell lymphoma, while T-cell lymphoma is extremely rare. We encountered a patient with primary gastric T-cell malignant lymphoma who, although demonstrating a very rare phenomenon, was negative for antihuman T-lymphotropic virus type 1 antibody. A 73-year-old man was admitted to the hospital with the chief complaint of upper abdominal pain. The primary lesion was a type 3 tumor located at the cardia to the posterior wall of the upper body of the stomach, which had invaded the tail of the pancreas and a part of the transverse colon. A total gastrectomy, pancreatosplenectomy, and partial resection of the transverse colon were performed. The surgical section contained a giant ulcerative lesion with its bank cleaved, and a histological examination revealed a diffuse, small cell (Lymphoma Study Group classification) malignant lymphoma. An immunohistochemical analysis of the surgical specimen was positive for LCA/CD45, UCLH-1/CD45RO, and Leu-4/CD3, and negative for L-26/CD20, and it was diagnosed to be primary gastric T-cell malignant lymphoma.

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  • Identification and Characterization of a Synaptojanin 2 Splice Isoform Predominantly Expressed in Nerve Terminals 査読

    Yasuo Nemoto, Markus R. Wenk, Masami Watanabe, Laurie Daniell, Tomoe Murakami, Niels Ringstad, Hiroshi Yamada, Kohji Takei, Pietro De Camilli

    Journal of Biological Chemistry   276 ( 44 )   41133 - 41142   2001年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have previously identified synaptojanin 1, a phosphoinositide phosphatase predominantly expressed in the nervous system, and synaptojanin 2, a broadly expressed isoform. Synaptojanin 1 is concentrated in nerve terminals, where it has been implicated in synaptic vesicle recycling and actin function. Synaptojanin 2A is targeted to mitochondria via a PDZ domain-mediated interaction. We have now characterized an alternatively spliced form of synaptojanin 2 that shares several properties with synaptojanin 1. This isoform, synaptojanin 2B, undergoes further alternative splicing to generate synaptojanin 2B1 and 2B2. Both amphiphysin and endophilin, two partners synaptojanin 1, bind synaptojanin 2B2, whereas only amphiphysin binds synaptojanin 2B1. Sequence similar to the endophilin-binding site in synaptojanin 1 is present only in synaptojanin 2B2, and this sequence was capable of affinity purifying endophilin from rat brain. The Sac1 domain of synaptojanin 2 exhibited phosphoinositide phosphatase activity very similar to that of the Sac1 domain of synaptojanin 1. Site-directed mutagenesis further illustrated its functional similarity to the catalytic domain of Sac1 proteins. Antibodies raised against the synaptojanin 2B-specific carboxyl-terminal region identified a 160-kDa protein in brain and testis. Immunofluorescence showed that synaptojanin 2B is localized at nerve terminals in brain and at the spermatid manchette in testis. Active Rac1 GTPase affects the intracellular localization of synaptojanin 2, but not of synaptojanin 1. These results suggest that synaptojanin 2B has a partially overlapping function with synaptojanin 1 in nerve terminals, with additional roles in neurons and other cells including spermatids.

    DOI: 10.1074/jbc.M106404200

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  • Expression of amphiphysin I in sertoli cells and its implication in spermatogenesis 査読

    M Watanabe, K Tsutsui, O Hosoya, K Tsutsui, H Kumon, A Tokunaga

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   287 ( 3 )   739 - 745   2001年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Amphiphysin I is a protein concentrated in nerve terminals and involved in the endocytosis of synaptic vesicle membrane. We show here that amphiphysin I is expressed in the rat testis, localized exclusively in the Sertoli cells. In the postnatal testicular development, expression of amphiphysin I was not evident at birth, but became significant at postnatal day 15 (P15), coinciding with the onset of spermatogenesis. The expression level of amphiphysin I increased 10-fold between P15 and P25 to reach the adult level. In adult testes reversibly damaged by ethane dimethane sulphonate administration, expression of amphiphysin I did not change following the damage, whereas the protein was transiently converted into its phosphorylated form. The increase in levels of phosphorylated amphiphysin I was closely associated with the severe histological damage to germ cells. The present findings suggest that amphiphysin I in Sertoli cells is involved in spermatogenesis, probably through endocytic processes. (C) 2001 Academic Press.

    DOI: 10.1006/bbrc.2001.5650

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  • 腎移植後の尿細胞診で6ヵ月以上持続するDecoy細胞陽性所見はBKウイルス腎症の発症予測に有効である

    関戸 崇了, 荒木 元朗, 吉永 香澄, 丸山 雄樹, 定平 卓也, 西村 慎吾, 和田 耕一郎, 渡部 昌実, 渡邉 豊彦, 田邊 克幸, 竹内 英実, 和田 淳, 柳井 広之, 那須 保友

    移植   56 ( 総会臨時 )   O17 - 3   2021年9月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本移植学会  

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  • 腎部分切除術を施行した巨大類上皮型腎血管筋脂肪腫の1例

    横山 周平, 富永 悠介, 高本 篤, 定平 卓也, 関戸 崇了, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 柳井 広之, 那須 保友

    西日本泌尿器科   83 ( 3 )   175 - 180   2021年8月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

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  • 腎門部に発生した粘液嚢胞腺癌の1例

    三宅 修司, 岩田 健宏, 長尾 賢太郎, 河田 達志, 富永 悠介, 定平 卓也, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 久保 寿夫, 柳井 広之, 那須 保友

    西日本泌尿器科   83 ( 2 )   100 - 105   2021年6月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

    症例は79歳,男性。2年前に検診にて左腎嚢胞と診断され近医で経過観察となっていたが,増大傾向であったため当科紹介となった。造影CT検査でBosniak分類category IVの左嚢胞性腎癌を疑い,腹腔鏡下左腎摘除術を施行した。術後病理結果から,粘液嚢胞腺癌(Mucinous cystadenocarcinoma)と診断した。術後補助化学療法は行わずに経過観察としていたが,術後3ヵ月後に多発肺転移が出現し,化学療法(カルボプラチン+パクリタキセル)を開始した。5コース投与後の肺転移はSDであったため,一旦化学療法中止で経過観察の方針としたが,5ヵ月後に肺転移は増大傾向を認めたため術後14ヵ月目よりニボルマブの投与を開始した。ニボルマブ2コース投与後のCTで肺転移は縮小し,5コース投与後もPRを維持しているため現在も投与継続中である。(著者抄録)

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  • 若年発症の前立腺炎症性偽腫瘍の1例

    佐久間 貴文, 丸山 雄樹, 定平 卓也, 高本 篤, 和田 耕一郎, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡辺 豊彦, 那須 保友

    西日本泌尿器科   83 ( 1 )   54 - 58   2021年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

    症例は19歳,男性。抗菌薬投与で改善しない排尿障害,排尿時痛を主訴に前医を受診。MRIで前立腺のT1強調像,T2強調像ともに低信号で,造影効果を伴う膀胱内に突出する腫瘤を指摘され当院紹介となった。血液,尿検査では特記事項なく,尿培養,尿細胞診は陰性であった。PSAを含め腫瘍マーカーの有意な上昇を認めなかった。膀胱鏡検査では前立腺部尿道に約35mmの非乳頭状広基性腫瘍を認めた。造影CTでは前立腺部にMRI同様の所見を認め,リンパ節腫大及び遠隔転移は認めなかった。排尿障害改善及び組織検査目的に経尿道的前立腺切除術(TUR-P)を施行した。切除組織は長紡錘形細胞の束状の増殖とリンパ球,形質細胞浸潤を認め,免疫染色でALK(anaplastic lymphoma kinase)陽性,α-smooth muscle actinが少数の細胞で陽性であり,前立腺炎症性偽腫瘍(inflammatory pseudtumor:IPT)と診断した。局所再発の可能性はあるものの,遠隔転移の可能性は低く,排尿状態の改善を得られたため経過観察の方針とした。術後10ヵ月現在で腫瘍の再燃を認めていない。(著者抄録)

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  • 高血圧・糖尿病に焦点を当てたマージナルドナーからの生体腎移植

    吉永 香澄, 荒木 元朗, 関戸 崇了, 和田里 章悟, 丸山 雄樹, 定平 卓也, 窪田 理沙, 西村 慎吾, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 竹内 英実, 田邉 克幸, 森永 裕士, 杉山 斉, 和田 淳, 渡部 昌実, 渡邉 豊彦, 那須 保友

    日本臨床腎移植学会プログラム・抄録集   54回   193 - 193   2021年2月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本臨床腎移植学会  

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  • 神経線維腫症1型に合併した後腹膜悪性末梢神経鞘腫瘍の1例

    宗田 大二郎, 岩田 健宏, 定平 卓也, 富永 悠介, 片山 聡, 西村 慎吾, 高本 篤, 佐古 智子, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友, 中田 英二, 柳井 広之

    西日本泌尿器科   82 ( 6 )   596 - 600   2021年2月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

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  • 【腎盂・尿管癌の治療を考える】腎盂・尿管癌における腹腔鏡下腎尿管全摘除術の適応

    吉永 香澄, 荒木 元朗, 和田里 章悟, 丸山 雄樹, 光井 洋介, 窪田 理沙, 定平 卓也, 岩田 健宏, 西村 慎吾, 高本 篤, 和田 耕一郎, 佐古 智子, 枝村 康平, 小林 泰之, 渡部 昌実, 渡辺 豊彦, 那須 保友

    泌尿器外科   33 ( 5 )   455 - 461   2020年5月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:医学図書出版(株)  

    切除可能な腎盂・尿管癌において、外科的治療の標準術式は腎尿管全摘除術・膀胱部分切除術である。腹腔鏡手術は開放手術と比較して低侵襲であり、低リスク症例では前者が選択される傾向にあるが、pT3以上やリンパ節転移が疑われる症例では開放手術が推奨されている。また、腎機能に問題がある場合などに腎温存療法や化学療法が選択されることもある。本稿では腎盂・尿管癌における腹腔鏡手術の適応について考察する。(著者抄録)

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  • 後腹膜悪性末梢神経鞘腫の1例

    宗田 大二郎, 高本 篤, 荒木 元朗, 角南 亮輔, 関戸 崇了, 佐久間 貴文, 和田里 章悟, 吉永 香澄, 丸山 雄樹, 光井 洋介, 富永 悠介, 大岩 裕子, 窪田 理沙, 定平 卓也, 片山 聡, 岩田 健宏, 西村 慎吾, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   82 ( 1 )   173 - 173   2020年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

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  • 岡山大学病院における進行性尿路上皮癌に対するpembrolizumabの治療経験

    富永 悠介, 高本 篤, 角南 亮輔, 関戸 崇了, 和田里 章悟, 河村 香澄, 丸山 雄樹, 光井 洋介, 大岩 裕子, 窪田 理沙, 定平 卓也, 片山 聡, 岩田 健宏, 西村 慎吾, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   81 ( 6 )   656 - 656   2019年12月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

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  • S100A11 contributes to tumor progression with cross talking between muscle invasive bladder cancer cells and fibroblasts

    光井 洋介, 定平 卓也, 渡部 昌実, 丸山 雄樹, 荒木 元朗, 渡邉 豊彦, 阪口 政清, 那須 保友

    西日本泌尿器科   81 ( 増刊 )   138 - 138   2019年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

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  • 症例から学ぶ 治療変遷から読み解く腎癌治療 何を、どこまで、どのように? 下大静脈腫瘍塞栓を伴う腎腫瘍の新しい手術アプローチ

    荒木 元朗, 小林 泰之, 枝村 康平, 角南 亮輔, 関戸 崇了, 和田里 章悟, 河村 香澄, 丸山 雄樹, 光井 洋介, 大岩 裕子, 窪田 理沙, 定平 卓也, 片山 聡, 岩田 健宏, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 渡辺 豊彦, 渡部 昌実, 那須 保友, 楳田 佑三, 八木 孝仁

    西日本泌尿器科   81 ( 増刊 )   113 - 113   2019年10月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:西日本泌尿器科学会  

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  • ロボット補助腹腔鏡下前立腺全摘術後尿失禁の予測因子としての骨盤MRIパラメーターの有用性

    定平 卓也, 河村 香澄, 丸山 雄樹, 光井 洋介, 和田 耕一郎, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友

    日本排尿機能学会誌   30 ( 1 )   321 - 321   2019年9月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本排尿機能学会  

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  • 前立腺癌に対するロボット支援前立腺全摘除術における前方・後方アプローチ間での術後QOLの比較

    丸山 雄樹, 定平 卓也, 荒木 元朗, 河村 香澄, 光井 洋介, 和田 耕一郎, 谷本 竜太, 小林 泰之, 渡部 昌実, 渡邊 豊彦, 那須 保友

    日本排尿機能学会誌   30 ( 1 )   255 - 255   2019年9月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本排尿機能学会  

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  • サルコペニアが前立腺全摘除後の排尿関連QoLに与える影響 Expanded Prostate Cancer Index Compositeを用いた経時的変化

    光井 洋介, 渡邉 豊彦, 定平 卓也, 丸山 雄樹, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 那須 保友

    日本排尿機能学会誌   30 ( 1 )   255 - 255   2019年9月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本排尿機能学会  

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  • 当院におけるニボルマブ+イピリムマブの初期経験

    片山 聡, 高本 篤, 関戸 崇了, 角南 亮輔, 佐久間 貴文, 和田里 章悟, 河村 香澄, 丸山 雄樹, 光井 洋介, 窪田 理沙, 大岩 裕子, 定平 卓也, 岩田 健宏, 西村 慎吾, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   81 ( 4 )   483 - 484   2019年8月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

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  • 消化器癌による転移性尿管腫瘍の2例

    河村 香澄, 荒木 元朗, 定平 卓也, 丸山 雄樹, 光井 洋介, 西村 慎吾, 高本 篤, 和田 耕一郎, 谷本 竜太, 杉本 盛人, 小林 泰之, 渡部 昌実, 渡辺 豊彦, 那須 保友, 柳井 広之

    西日本泌尿器科   81 ( 4 )   461 - 466   2019年8月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:西日本泌尿器科学会  

    消化器癌を原発とする転移性尿管腫瘍の2例を経験したため報告する。【症例1】64歳、男性。2007年9月、下行結腸癌に対して下行結腸切除術を施行した。2014年、術後のCTで右尿管腫瘍を指摘され当科へ紹介となった。右尿管鏡検査時の生検病理結果より下行結腸癌の尿管転移と診断し、開腹腫瘍摘出術を行った。術後4ヵ月の時点で肝転移を認めたためTS-1 120mg内服療法を14ヵ月行い、様々な変更を経て現在はXELIRI + Bevacizumab療法8コース目を行っている。肝転移は緩徐に増大中である。【症例2】62歳、男性。2014年12月、多発胃癌に対して幽門側胃切除術、胆嚢摘出術およびRoux-en-Y再建術を施行し、術後TS-1 100mg内服療法を1年間行った。2017年、CTで右水腎症と尿管壁肥厚を指摘され、右尿管鏡検査を行うも狭窄が強く組織は採取できず、検査時の分腎尿細胞診はclass IVであった。再施行した右尿管鏡検査において狭窄尾側を生検したところ浸潤性尿路上皮癌の診断であったため、後腹膜鏡下右腎尿管摘除術を施行した。右尿管は腹膜およびS状結腸と著しく癒着し、漿膜ごと摘除した。病理結果は胃癌の右尿管転移であった。術後weekly PTX 100mgを開始したが骨転移の出現や腹膜転移の進行を認め、PTX + Ramucirumab 1コース施行した後に抗PD-1抗体180mgを5コース行ったが全身状態は徐々に悪化した。術後7ヵ月で緩和療法に移行し、術後11ヵ月で永眠された。転移性尿管腫瘍は術前生検しても診断が難しい場合がある。予後不良な疾患であり、悪性疾患の既往のある尿管腫瘍は転移性尿管腫瘍も鑑別に挙げる必要がある。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01004&link_issn=&doc_id=20190823210008&doc_link_id=%2Fer9niuro%2F2019%2F008104%2F008%2F0461-0466%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2019%2F008104%2F008%2F0461-0466%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 経尿道的砕石術(TUL)を施行した小児腎結石症の1例

    佐久間貴文, 和田耕一郎, 本郷智拡, 前原貴典, 高本篤, 坪井一朗, 松尾聡子, 三井將雄, 和田里章悟, 河村香澄, 丸山雄樹, 光井洋介, 窪田理沙, 大岩裕子, 定平卓也, 西村慎吾, 佐古智子, 枝村康平, 小林泰之, 石井亜矢乃, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

    西日本泌尿器科   81 ( 2 )   243‐244   2019年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

    J-GLOBAL

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  • がん・生殖の現状と今後の展望地域ネットワークにおける泌尿器科医の役割は何か? 岡山大学病院におけるがん生殖医療の現状と課題

    佐古 智子, 杉本 盛人, 高山 修, 中塚 幹也, 和田 耕一郎, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡辺 豊彦, 那須 保友

    日本泌尿器科学会総会   107回   SY20 - 4   2019年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 前立腺全摘除術前における針生検病理標本second-lookの有用性

    定平 卓也, 丸山 雄樹, 光井 洋介, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友

    日本泌尿器科学会総会   107回   PP1 - 070   2019年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 胚細胞腫瘍におけるブレオマイシン関連薬剤性肺障害の炎症性バイオマーカーの探索

    丸山 雄樹, 定平 卓也, 荒木 元朗, 光井 洋介, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 渡部 昌実, 渡邉 豊彦, 那須 保友

    日本泌尿器科学会総会   107回   PP1 - 137   2019年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • PNにおける腎機能温存は生命予後に寄与しているのか? 腎部分切除術における腎機能温存と心血管イベントの関連性の検討

    枝村 康平, 窪田 理沙, 大岩 裕子, 定平 卓也, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 小林 泰之, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友

    日本泌尿器科学会総会   107回   SY15 - 3   2019年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • ロボット支援腎部分切除術における切除皮質体積の重要性 切除組織からの3D再構築による精密測定を用いて

    光井 洋介, 定平 卓也, 荒木 元朗, 丸山 雄樹, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 枝村 康平, 小林 泰之, 渡部 昌実, 渡邉 豊彦, 那須 保友

    日本泌尿器科学会総会   107回   AOP - 105   2019年4月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 尿道腫瘤を認めたメトトレキサート関連リンパ増殖性疾患の1例

    河村香澄, 丸山雄樹, 定平卓也, 光井洋介, 西村慎吾, 高本篤, 甲斐誠二, 和田耕一郎, 谷本竜太, 杉本盛人, 小林泰之, 荒木元朗, 渡部昌実, 渡辺豊彦, 那須保友, 田中健大

    西日本泌尿器科   80 ( 12 )   678‐683 - 683   2018年12月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

    症例は64歳、女性。2007年に関節リウマチの診断を受け、2008年よりメトトレキサート(MTX)内服中であった。2015年に繰り返す発熱で近医を受診。CTで子宮頸癌および両肺多発転移を疑われた。当院婦人科で子宮頸部パンチ生検を施行するも悪性所見なく、肺結節も自然消退したため経過観察となっていた。2017年2月、症状が再燃し近医を受診した。CTで左下葉結節影、右肺門リンパ節腫脹、腹腔内リンパ節腫脹および左腎盂拡張を認め、PET-CTで左腎門部リンパ節、尿道、上咽頭に高集積を認めた。MTX関連リンパ増殖性疾患(MTX-LPD)を疑い、施行した上咽頭生検はHodgkinリンパ腫の像を呈し、EBER-ISH陽性であった。MTX中止後は左尿管病変および尿道病変に著変はないものの、肺腫瘤とリンパ節は縮小傾向で現在経過観察中である。(著者抄録)

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  • 超細径HDIGスコープを用いた直視下腎杯穿刺とPCNLの初期成績

    和田耕一郎, 公文裕巳, 谷本竜太, 荒木元朗, 本郷智拡, 三井將雄, 松尾聡子, 坪井一朗, 佐久間貴文, 和田里章悟, 河村香澄, 丸山雄樹, 光井洋介, 前原貴典, 窪田理沙, 大岩裕子, 定平卓也, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 杉本盛人, 小林泰之, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友

    西日本泌尿器科   80 ( 12 )   700 - 700   2018年12月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

    J-GLOBAL

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  • 新規抗癌ウイルス医薬の開発とその局所投与法の最適化

    渡部 昌実

    上原記念生命科学財団研究報告集   32   1 - 4   2018年12月

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:日本語   出版者・発行元:(公財)上原記念生命科学財団  

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  • 再発性尿路感染症に対するプロバイオティクスの有効性

    定平卓也, 和田耕一郎, 三井將雄, 石井亜矢乃, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

    西日本泌尿器科   80 ( 10 )   505‐509 - 509   2018年10月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

    尿路感染症に対する治療として中心的な役割を果たしてきた抗菌化学療法は大きな転機を迎えている。世界的な時流として耐性菌の問題や医療経済的にも抗菌薬の使用量を減少させる方向に移行している。尿路感染症においても例外ではなく、そのマネジメントに関して治療法の見直しだけでなく予防の重要性についての議論がなされている。そのうち、これまでに様々な臨床研究において有効性が確認されつつあるプロバイオティクスが抗菌薬とは異なる尿路感染症対策として注目されている。健常な閉経前の女性の腟内においては、基本的に乳酸菌が細菌叢(フローラ)を形成しているが、月経中や閉経後は乳酸菌が減少して腸内細菌が腟内に定着することとなる。その腟がリザーバーとなって細菌を供給し、頻繁に尿路の逆行性感染を引き起こすと考えられている。すなわち、腟内を乳酸菌中心のフローラに保つことで尿路感染症の再発(反復)リスクが低くなることが期待でき、実際にプロバイオティクスを用いた多くの研究が行われている。我々が現在行っている乳酸菌製剤のほか、プロバイオティクスの経口摂取が腟内フローラに与える影響に関しても検証が進んでおり、プロバイオティクスが尿路感染症の予防や治療に寄与することが期待されている。(著者抄録)

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  • 前立腺に発生したSFT(Solitary fibrous tumor)の1例

    本郷 智拡, 高本 篤, 三井 將雄, 松尾 聡子, 坪井 一朗, 佐久間 貴文, 和田里 章悟, 河村 香澄, 丸山 雄樹, 光井 洋介, 前原 貴典, 窪田 理沙, 大岩 裕子, 定平 卓也, 西村 慎吾, 佐古 智子, 和田 耕一郎, 谷本 竜太, 杉本 盛人, 小林 泰之, 石井 亜矢乃, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   80 ( 9 )   497 - 497   2018年9月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 排尿障害を伴う女性尿道憩室に対して手術治療を行った1例

    松尾 聡子, 杉本 盛人, 佐久間 貴文, 坪井 一朗, 本郷 智拡, 三井 將雄, 河村 香澄, 和田里 章悟, 丸山 雄樹, 光井 洋介, 定平 卓也, 前原 貴典, 大岩 裕子, 西村 慎吾, 高本 篤, 佐古 智子, 和田 耕一郎, 谷本 竜太, 小林 泰之, 荒木 元朗, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友, 中村 あや, 津島 知靖

    西日本泌尿器科   80 ( 9 )   495 - 495   2018年9月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 尿路感染を契機とした化膿性脊椎炎の3例

    森 聰博, 和田 耕一郎, 定平 卓也, 西村 慎吾, 藤尾 圭, 高本 篤, 堀川 雄平, 谷本 竜太, 杉本 盛人, 小林 泰之, 佐々木 克己, 荒木 元朗, 渡部 昌実, 江原 伸, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   80 ( 8 )   428 - 433   2018年8月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

    化膿性脊椎炎は尿路感染症や尿性敗血症(ウロセプシス)が原因の一つとなる。今回、尿路感染症の治療経過中に発症し、保存的加療により治癒した化膿性脊椎炎の3例を経験した。いずれの症例も腎盂腎炎に対する抗菌薬の投与中に腰背部痛が遷延もしくは増強し、発症から9日以上経過した複数回目のMRIで診断し得た。尿路感染症治療中に持続、または増強する背部痛、腰痛には注意が必要であり、化膿性脊椎炎を疑って複数回の画像診断を行う必要があると考えられた。(著者抄録)

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  • 膵がん進展に導く膵がん細胞 間質線維芽細胞クロストークを介在する分泌性S100A11 受容体RAGE連携の役割

    光井 洋介, 山本 健一, Sumardika I Wayan, 木下 理恵, 村田 等, 二見 淳一郎, 高松 仁, 山本 靖彦, 西堀 正洋, 豊岡 伸一, 渡部 昌実, 那須 保友, 阪口 政清

    日本がん免疫学会総会プログラム・抄録集   22回   156 - 156   2018年7月

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    記述言語:日本語   出版者・発行元:日本がん免疫学会  

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  • 岡山大学におけるロボット支援腹腔鏡下前立腺全摘除術の治療成績

    谷本 竜太, 小林 宏州, 河村 香澄, 和田里 章悟, 丸山 雄樹, 光井 洋介, 前原 貴典, 大岩 裕子, 定平 卓也, 岩田 健宏, 西村 慎吾, 高本 篤, 松本 裕子, 甲斐 誠二, 和田 耕一郎, 杉本 盛人, 荒木 元朗, 小林 泰之, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   80 ( 5 )   246 - 246   2018年5月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 転移性尿管腫瘍の2例

    河村 香澄, 杉本 盛人, 小林 宏州, 和田里 章悟, 丸山 雄樹, 光井 洋介, 前原 貴典, 大岩 裕子, 定平 卓也, 岩田 健宏, 西村 慎吾, 高本 篤, 甲斐 誠二, 和田 耕一郎, 谷本 竜太, 荒木 元朗, 小林 泰之, 石井 亜矢乃, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   80 ( 5 )   242 - 242   2018年5月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 岡山大学病院泌尿器科における腹腔鏡下尿膜管摘出術の治療経験

    前原 貴典, 杉本 盛人, 和田里 章悟, 河村 香澄, 小林 宏州, 丸山 雄樹, 光井 洋介, 大岩 裕子, 定平 卓也, 岩田 健宏, 西村 慎吾, 高本 篤, 甲斐 誠二, 和田 耕一郎, 谷本 竜太, 小林 泰之, 石井 亜矢乃, 荒木 元朗, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   80 ( 4 )   181 - 181   2018年4月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • INDUCTION OF PROSTATE CANCER STEM CELL PROPERTIES IN MOUSE INDUCED PLURIPOTENT STEM CELLS VIA DEFINED CARCINOMA NICHE AND TRACKING DRUG RESPONSE IN PRECLINICAL RESEARCH

    Naijin Xu, Xiezhao Li, Aibai Xu, Masami Watanabe, Peng Huang, Yasutomo Nasu, Chunxiao Liu

    JOURNAL OF UROLOGY   197 ( 4 )   E540 - E540   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

    Web of Science

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  • IMMUNE CHECKPOINT INHIBITOR COMBINED WITH THE GROWTH INHIBITOR LYCORINE SYNERGISTICALLY FUNCTION TO MEDIATE ANTI-TUMOR EFFECTS IN A MOUSE MODEL OF RENAL CELL CARCINOMA

    Xiezhao Li, Naijin Xu, Aibai Xu, Masami Watanabe, Peng Huang, Yasutomo Nasu, Chunxiao Liu

    JOURNAL OF UROLOGY   197 ( 4 )   E963 - E963   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

    Web of Science

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  • REAL-TIME MONITORING OF TUMOR PROGRESSION AND DRUG RESPONSES IN A PRECLINICAL MOUSE MODEL OF PROSTATE CANCER

    Peng Huang, Peng Xu, Xiezhao Li, Naijin Xu, Abai Xu, Masami Watanabe, Hiromi Kumon, Chunxiao Liu, Yasutomo Nasu

    JOURNAL OF UROLOGY   197 ( 4 )   E598 - E598   2017年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

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  • 後腹膜線維症に対し尿管剥離術および大網ラッピングを施行した1例

    児島 宏典, 荒木 元朗, 藤尾 圭, 吉岡 貴史, 森 聰博, 高本 篤, 堀川 雄平, 杉本 盛人, 和田 耕一郎, 佐々木 克己, 小林 康之, 江原 伸, 渡部 昌実, 渡邉 豊彦, 那須 保友

    西日本泌尿器科   79 ( 1 )   12 - 15   2017年1月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

    症例は62歳、男性。全身倦怠感で来院。CT、MRIにて後腹膜線維症による両側水腎症、腹部大動脈瘤(35mm)、左総腸骨動脈瘤(23mm)、右総腸骨動脈瘤(16mm)を認めた。血清Crは5.3mg/dLで腎後性腎不全の状態であったため両側尿管ステントを留置したところ血清Crは1.6mg/dLに低下した。その後3ヵ月ごとの尿管ステント交換を20ヵ月行った。経過中プレドニゾロン内服(30mg/dからの漸減5mg/d、11ヵ月)を行ったがステント抜去不可であった。またステロイド糖尿病を発症した。経過中両側尿管の狭窄が悪化、ガイドワイヤー挿入困難となった。将来的な尿管動脈瘻の出現も懸念されたため右尿管剥離、大網ラッピングを行った。Mag3腎シンチで左腎は無機能腎であったため同時に腎摘した。術後6週で尿管ステント抜去。術後9週において血清Crは1.3mg/dL、腎エコーで水腎grade II、Mag3腎シンチで3相形成が見られた。術後14ヵ月において血清Crは1.5mg/dL、腎エコーで水腎なく経過している。後腹膜線維症による水腎症に尿管剥離、大網ラッピングは有効な外科的治療である。(著者抄録)

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  • Ureterolysis with omental wrap for bilateral hydronephrosis secondary to retroperitoneal fibrosis

    Hironori Kojima, Motoo Araki, Kei Fujio, Takashi Yoshioka, Akihiro Mori, Atsushi Takamoto, Yuhei Horikawa, Morito Sugimoto, Koichiro Wada, Katsumi Sasaki, Yasuyuki Kobayashi, Shin Ebara, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

    Nishinihon Journal of Urology   79 ( 1 )   12 - 15   2017年

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  • 【新前立腺癌学-最新の基礎研究と診断・治療-】 臨床応用を目指した基礎研究 新規治療開発 遺伝子治療

    渡部 昌実, 定平 卓也, 那須 保友

    日本臨床   74 ( 増刊3 新前立腺癌学 )   221 - 225   2016年5月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • 2.新規治療開発 (2)遺伝子治療

    渡部昌実, 定平卓也, 那須保友

    新前立腺癌学―最新の基礎研究と診断・治療―   74 ( 3 )   221 - 225   2016年5月

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    記述言語:日本語  

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  • ADVANCED TWO-STEP TRANSCRIPTIONAL AMPLIFICATION AS A NOVEL SYSTEM FOR DETECTING VIABLE BLADDER CANCER CELLS

    Takuya Sadahira, Masami Watanabe, Motoo Araki, Shin Ebara, Toyohiko Watanabe, Yasutomo Nasu

    JOURNAL OF UROLOGY   195 ( 4 )   E610 - E610   2016年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

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  • ロボット補助腹腔鏡下前立腺全摘除術と前立腺密封小線源永久挿入療法後の排尿関連QOLの検討

    宗政 修平, 定平 卓也, 高本 篤, 藤尾 圭, 和田 耕一郎, 杉本 盛人, 佐々木 克己, 小林 泰之, 荒木 元朗, 渡部 昌実, 江原 伸, 渡辺 豊彦, 那須 保友

    日本泌尿器科学会総会   104回   PP3 - 240   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 緑色蛍光タンパク質発現プラスミドによる膀胱癌に対する新たな診断の有用性

    定平 卓也, 渡部 昌実, 荒木 元朗, 江原 伸, 渡辺 豊彦, 那須 保友

    日本泌尿器科学会総会   104回   PP2 - 042   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 精管結紮術27年後に精管精管吻合による精路再建を行い再疎通認められた一例

    杉本 盛人, 石井 和史, 倉橋 寛明, 松本 裕子, 渡部 昌実, 荒木 元朗, 渡邉 豊彦, 那須 保友

    日本生殖医学会雑誌   61 ( 1-2 )   72 - 72   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本生殖医学会  

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  • ロボット支援・開腹術における腎部分切除の工夫

    荒木 元朗, 小林 泰之, 井上 陽介, 児島 宏典, 光井 洋介, 宗政 修平, 定平 卓也, 吉岡 貴史, 有吉 勇一, 森 聰博, 藤尾 圭, 高本 篤, 松本 裕子, 堀川 雄平, 和田 耕一郎, 杉本 盛人, 佐々木 克己, 石井 亜矢乃, 渡部 昌実, 江原 伸, 渡辺 豊彦, 那須 保友

    西日本泌尿器科   78 ( 4 )   194 - 195   2016年4月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 難治性前立腺癌に対するREIC遺伝子医薬の開発

    渡部昌実, 定平卓也, 有吉勇一, 那須保友

    泌尿器外科   29 ( 4 )   361 - 364   2016年4月

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    記述言語:日本語  

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  • ロボット自家腎移植の検討

    荒木 元朗, 和田 耕一郎, 有吉 勇一, 平田 武志, 小林 泰之, 吉岡 貴史, 井上 陽介, 児島 宏典, 光井 洋介, 定平 卓也, 森 聰博, 藤尾 圭, 高本 篤, 松本 裕子, 堀川 雄平, 杉本 盛人, 佐々木 克己, 石井 亜矢乃, 渡部 昌実, 江原 伸, 渡辺 豊彦, 那須 保友, 公文 裕巳

    西日本泌尿器科   78 ( 3 )   136 - 136   2016年3月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 不完全な尿管ステント留置と移植腎動脈下極枝の閉塞により尿管穿孔を生じた生体腎移植の一例

    和田耕一郎, 荒木元朗, 有森千聖, 有吉勇一, 佐々木克己, 小林泰之, 渡部昌実, 江原 伸, 渡辺豊彦, 那須保友, 公文裕巳, 吉岡貴史

    腎移植・血管外科   26 ( 1 )   2016年

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  • 成長円錐におけるPKCαのコルタクチンリン酸化によるアクチン制御の可能性

    山田 浩司, 菊池 達也, 増本 年男, 魏 范研, 阿部 匡史, 竹田 哲也, 西木 禎一, 富澤 一仁, 渡部 昌実, 松井 秀樹, 竹居 孝二

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [1P1328] - [1P1328]   2015年12月

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    記述言語:英語   出版者・発行元:(公社)日本生化学会  

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  • 悪性胸膜中皮腫に対するREIC/Dkk-3遺伝子治療

    山本 寛斉, 枝園 和彦, 牧 佑歩, 宗 淳一, 大谷 真二, 三好 健太郎, 杉本 誠一郎, 山根 正修, 大藤 剛宏, 渡部 昌実, 那須 保友, 三好 新一郎, 豊岡 伸一

    肺癌   55 ( 5 )   502 - 502   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 精嚢造影併用の経尿道的内視鏡手術が診断治療に有用であった射精障害の一例

    杉本 盛人, 石井 和史, 光井 洋介, 吉岡 貴史, 倉橋 寛明, 松本 裕子, 瀬野 祐子, 小林 泰之, 渡部 昌実, 渡邊 豊彦, 那須 保友

    日本性機能学会雑誌   30 ( 2 )   198 - 198   2015年8月

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    記述言語:日本語   出版者・発行元:(一社)日本性機能学会  

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  • テストステロンエナント酸エステル注射液の供給停止状態でのLOH症候群の治療

    倉橋 寛明, 松本 裕子, 杉本 盛人, 石井 和史, 佐々木 克己, 荒木 元朗, 江原 伸, 賀来 春紀, 渡部 昌実, 渡邉 豊彦, 那須 保友, 公文 裕巳

    日本泌尿器科学会総会   103回   479 - 479   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • ハイリスク前立腺癌に対するネオアジュバントREIC遺伝子治療

    有吉 勇一, 定平 卓也, 高本 篤, 平田 武志, 佐々木 克己, 荒木 元朗, 渡部 昌実, 江原 伸, 渡辺 豊彦, 那須 保友, 公文 裕巳

    日本泌尿器科学会総会   103回   502 - 502   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • Adenovirus-Mediated Overexpression of REIC/DKK-3 Inhibits Cell Growth and Induces Apoptosis in Pancreatic Cancer and Hepatocellular Carcinoma

    Sawahara Hiroaki, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Masami Watanabe, Hiromi Kumon, Yasutomo Nasu, Kazuhide Yamamoto

    GASTROENTEROLOGY   148 ( 4 )   S954 - S954   2015年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 前立腺癌に対する新規免疫療法としてのREIC/Dkk-3遺伝子治療

    那須保友, 渡部昌実

    泌尿器外科   28 ( 7 )   1187 - 1190   2015年

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  • Anti-cancer effects of REIC/Dkk-3-encoding adenoviral vector for the treatment of non-small cell lung cancer

    Ken Suzawa, Shinichi Toyooka, Kazuhiko Shien, Norimitsu Tanaka, Masami Watanabe, Junichi Soh, Masakiyo Sakaguchi, Keitaro Matsuo, Hiromasa Yamamoto, Masashi Furukawa, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Nam-Ho Huh, Shinichiro Miyoshi, Hiromi Kumon

    CANCER RESEARCH   74 ( 19 )   2014年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-2879

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  • 社会的性自認に対して持続的な性別違和感を有し、ジェンダーセンターを受診した性分化疾患の3例

    松本 裕子, 杉本 盛人, 渡部 昌実, 倉橋 寛明, 荒木 元朗, 江原 伸, 渡邉 豊彦, 那須 保友, 公文 裕巳, 石井 和史

    日本性科学会雑誌   32 ( 2 )   152 - 152   2014年9月

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    記述言語:日本語   出版者・発行元:日本性科学会  

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  • 勃起障害に対する陰茎海綿体自己注射の初期経験

    松本 裕子, 杉本 盛人, 渡部 昌実, 倉橋 寛明, 荒木 元朗, 江原 伸, 渡邉 豊彦, 那須 保友, 公文 裕巳, 石井 和史

    日本性機能学会雑誌   29 ( 2 )   182 - 182   2014年8月

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    記述言語:日本語   出版者・発行元:(一社)日本性機能学会  

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  • ADENOVIRUS-MEDIATED INTERLEUKIN-12 GENE THERAPY FOR CASTRATION RESISTANT PROSTATE CANCER: REPORT OF A CLINICALLY RESPONDED CASE

    Taiki Kanbara, Yasutomo Nasu, Katsumi Sasaki, Haruki Kaku, Masami Watanabe, Toyohiko Wananabe, Hiromi Kumon, Malcolm K. Brenner

    JOURNAL OF GENE MEDICINE   16 ( 7-8 )   240 - 241   2014年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • A PHASE I/II STUDY OF REDUCED EXPRESSION IN IMMORTALIZED CELLS (REIC/DKK-3) GENE THERAPY FOR PROSTATE CANCER; INTERIM REPORT

    Katsumi Sasaki, Yasutomo Nasu, Haruki Kaku, Masami Watanabe, Taiki Kanbara, Toyohiko Wananabe, Hiromi Kumon

    JOURNAL OF GENE MEDICINE   16 ( 7-8 )   239 - 240   2014年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • The Efficacy of REIC/DKK-3 Gene Therapy for Pancreatic Cancer

    Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Sigeru Horiguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

    GASTROENTEROLOGY   146 ( 5 )   S301 - S301   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • A Case Report Showing Dramatic Response With In-Situ Ad-REIC Gene Therapy in a Patient With Metastatic CRPC Following Chemotherapy

    Yuichi Ariyoshi, Kathumi Sasaki, Takao Hiraki, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon

    MOLECULAR THERAPY   22   S103 - S103   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:NATURE PUBLISHING GROUP  

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  • 超高効率遺伝子発現システムを用いた次世代REIC遺伝子治療の開発

    渡部 昌実, 阪口 政清, 賀来 春紀, 佐々木 克己, 高本 篤, 有吉 勇一, 杉本 盛人, 江原 伸, 渡辺 豊彦, 許 南浩, 那須 保友, 公文 裕巳

    日本泌尿器科学会総会   102回   621 - 621   2014年4月

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    記述言語:日本語   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 岡山大学における前立腺癌に対するReduced Expression in Immortalized Cells遺伝子治療臨床研究 CRPC著効例の報告

    佐々木 克己, 有吉 勇一, 高本 篤, 江原 伸, 渡部 昌実, 賀来 春紀, 柳井 広之, 渡辺 豊彦, 那須 保友, 公文 裕巳

    日本泌尿器科学会総会   102回   621 - 621   2014年4月

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    記述言語:日本語   出版者・発行元:(一社)日本泌尿器科学会総会事務局  

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  • 岡山大学泌尿器科における前立腺癌に対するREIC遺伝子治療臨床研究 CRPC著効例の報告

    有吉 勇一, 高本 篤, 谷本 竜太, 佐々木 克己, 江原 伸, 賀来 春紀, 渡部 昌実, 渡邉 豊彦, 那須 保友, 公文 裕巳

    西日本泌尿器科   76 ( 1 )   33 - 33   2014年1月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 小胞体ストレスにより癌細胞アポトーシスを誘導するREIC/Dkk‐3遺伝子治療が抗腫瘍免疫に及ぼす影響の検討

    有吉勇一, 定平卓也, 渡部昌実, 那須保友, 榮川伸吾, 山崎千尋, 一柳朋子, 鵜殿平一郎, 公文裕巳

    臨床ストレス応答学会大会抄録集   9th   55   2014年

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    記述言語:日本語  

    J-GLOBAL

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  • Advanced two-step transcriptional amplification as a novel method for cancer-specific gene expression and imaging

    H. Kaku, H. Ueki, Y. Ariyoshi, S. Li, P. Huang, Y. Nasu, H. Kumon, M. Watanabe

    HUMAN GENE THERAPY   24 ( 12 )   A154 - A154   2013年12月

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  • ANALYSIS OF COMBINATION THERAPY OF THE ADENOVIRUS VECTOR CARRYING REIC/Dkk-3 (Ad-REIC) AND THE INTEGRIN ANTAGONIST CILENGITIDE

    Yosuke Shimazu, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Kentaro Fujii, Manabu Onishi, Joji Ishida, Tetsuo Oka, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Isao Date

    NEURO-ONCOLOGY   15   58 - 58   2013年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS INC  

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  • DOSE-RESPONSE ANALYSIS OF TESTOSTERONE REPLACEMENT THERAPY IN PATIENTS WITH FEMALE TO MALE GENDER IDENTITY DISORDER

    Morito Sugimoto, Kazushi Ishii, Hiroaki Kurahashi, Yuko Matumoto, Tomoko Sako, Aya Nakamura, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon

    JOURNAL OF SEXUAL MEDICINE   10   236 - 236   2013年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY-BLACKWELL  

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  • PS-109-6 REIC/Dickkopf-3 shows anti-proliferative effect for non-small cell lung cancer cells with negative phosphorylated-Akt status

    Tanaka Norimitsu, Toyooka Shinichi, Watanabe Masami, Soh Junichi, Sakaguchi Masakiyo, Tsukuda Kazunori, Asano Hiroaki, Shien Kazuhiko, Furukawa Masashi, Maki Yuho, Muraoka Takayuki, Huh Nam-ho, Nasu Yasutomo, Kumon Hiromi, Miyoshi Shinichiro

    日本外科学会雑誌   113 ( 2 )   710 - 710   2012年3月

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    CiNii Article

    CiNii Books

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  • 外科領域における先端技術・治療の開発 マウス誘導膵幹細胞(Induced Pancreatic Stem(iPaS) Cells)の樹立

    野口 洋文, 齊藤 一誠, 片岡 仁美, 渡部 昌実, 藤原 俊義

    日本外科学会雑誌   113 ( 臨増2 )   124 - 124   2012年3月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • A phase I/II study of adenovirus-mediated reduced expression in immortalized cells (REIC/DKK-3) gene therapy for prostate cancer: An interim report.

    Katsumi Sasaki, Yasutomo Nasu, Masami Watanabe, Haruki Kaku, Ryuta Tanimoto, Daiki Kanbara, Toyohiko Watanabe, Hiroyuki Yanai, Hiromi Kumon

    JOURNAL OF CLINICAL ONCOLOGY   30 ( 5 )   2012年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • マウス膵幹細胞の樹立効率の検討

    野口 洋文, 齊藤 一誠, 片岡 仁美, 渡部 昌実, 藤原 俊義

    Organ Biology   18 ( 2 )   251 - 251   2011年10月

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    記述言語:日本語   出版者・発行元:(一社)日本臓器保存生物医学会  

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  • マウス膵幹細胞の培養条件の検討

    野口 洋文, 齊藤 一誠, 片岡 仁美, 渡部 昌実, 藤原 俊義

    Organ Biology   18 ( 2 )   250 - 250   2011年10月

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    記述言語:日本語   出版者・発行元:(一社)日本臓器保存生物医学会  

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  • A phase I/II study of adenovirus-mediated interleukin-12 gene therapy for hormone refractory prostate cancer: An interim report

    K. Sasaki, Y. Nasu, H. Kaku, M. Watanabe, H. Nose, D. Kanbara, T. Saika, H. Kumon

    JOURNAL OF CLINICAL ONCOLOGY   29 ( 7 )   2011年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • Ⅱ臨床 前立腺癌の治療 遺伝子治療 自殺遺伝子・免疫遺伝子を用いた遺伝子治療

    那須保友, 佐々木克己, 賀来春紀, 渡部昌実, 公文裕巳

    前立腺癌(第2版)-基礎・臨床研究のアップデート-   69 ( 5 )   554 - 558   2011年

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  • Ⅱ臨床 前立腺癌の治療 遺伝子治療 REIC/Dkk-3遺伝子治療

    渡部昌実, 賀来春紀, 黄 鵬, 那須保友, 公文裕巳

    前立腺癌(第2版)-基礎・臨床研究のアップデート-   69 ( 5 )   559 - 563   2011年

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  • 特集 専門医のための性分化疾患講座 思春期以降の「性同一性障害」とその包括的治療

    石井和史, 杉本盛人, 渡部昌実, 公文裕巳, 松本洋輔, 中塚幹也, 難波祐三郎

    臨床泌尿器科   65 ( 12 )   941 - 947   2011年

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  • REIC/DKK-3 STABLE TRANSFECTANT INDICATES ANTI-TUMOR PHENOTYPE IN MOUSE PROSTATE CANCER RM9 CELLS

    Haruki Kaku, Jie Chen, Masami Watanabe, Peng Huang, Yuji Kashiwakura, Fernando Abarzua, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

    JOURNAL OF GENE MEDICINE   11 ( 12 )   1182 - 1182   2009年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS LTD  

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  • REIC/Dkk-3 in normal fibroblasts suppresses tumor growth via induction of interleukin-7.

    Chen J, Watanabe M, Huang P, Sakaguchi M, Ochiai K, Nasu Y, Ouchida M, Huh NH, Shimizu K, Kashiwakura Y, Kaku H, Kumon H

    Int J Mol Med   24 ( 6 )   789 - 794   2009年

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  • REIC/Dkk-3遺伝子治療の正常細胞を介する抗腫瘍効果(Transduction of gene therapeutic REIC/Dkk-3 into normal cells provides another arm for tumor suppression in vivo)

    片岡 健, 阪口 政清, Fernando Abarzua, 谷本 竜太, 渡部 昌実, 村田 等, 那須 保友, 公文 裕巳, 許 南浩

    日本癌学会総会記事   67回   93 - 93   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 再燃進行前立腺がんの治療の現状と展望 再燃前立腺がんに対する遺伝子治療の現況と展望

    那須 保友, 賀来 春紀, 渡部 昌実, 枝村 康平, 谷本 竜太, Abaruz Fernando, 黄 鵬, 佐々木 克己, 雑賀 隆史, 公文 裕巳

    泌尿器外科   21 ( 8 )   1049 - 1051   2008年8月

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    記述言語:日本語   出版者・発行元:医学図書出版(株)  

    再燃前立腺がんに対する新たな治療法として遺伝子治療の基礎研究は分子生物学の進歩に伴いその成果を挙げてきた。さらにこれらの基礎研究の成果を臨床に還元するための研究(トランスレーショナルリサーチ)としてわれわれは遺伝子治療臨床研究を実施してきた。われわれが実施してきた自殺遺伝子としてのHSV-tk遺伝子、Interleukin-12遺伝子、腫瘍融解アデノウイルス、新規がん抑制遺伝子REICを用いた遺伝子治療研究の成果を概説することで再燃前立腺がんに対する遺伝子治療の現況とその展望を述べた。(著者抄録)

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  • 前立腺癌基礎研究の最前線 岡山大学における前立腺癌遺伝子治療研究の現況と展望 ベーシックリサーチからトランスレーショナルリサーチへ

    賀来 春紀, 藤原 俊義, 公文 裕巳, 渡部 昌実, 黄 鵬, 陳 潔, 谷本 竜太, フェルナンド・アバルスア, 枝村 康平, 真鍋 大輔, 江原 伸, 雑賀 隆史, 那須 保友

    西日本泌尿器科   69 ( 4 )   221 - 229   2007年4月

  • アデノ随伴ウィルスベクターを用いた局所前立腺癌遺伝子治療の可能性:マスピンの長期発現により腫瘍増殖が効率的に抑制された

    渡部昌実

    岡山医学会雑誌   第119   1 - 5   2007年

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  • PP-245 Telomerase-Specific Replication-Selective Virotherapy for Prostate Cancer

    黄 鵬, 渡部 昌実, 陳 潔, 賀来 春紀, 那須 保友, 雑賀 隆史, 藤原 俊義, 浦田 泰生, 公文 裕巳

    日本泌尿器科学会雑誌   98 ( 2 )   2007年

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    記述言語:英語   出版者・発行元:一般社団法人 日本泌尿器科学会  

    CiNii Article

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  • Therapeutic Activities of IL-12 Gene-Modified Macrophages Embedded in Gelatin Matrix Hemostatic Sealant (FloSeal (R)) in a Mouse Model of Residual Prostate Cancer

    Ken-ichi Tabata, Masami Watanabe, Takefumi Satoh, Wei-hau Tian, Hongyu Wang, ElMoataz Abdel Fattah, Guang Yang, Daniel Floryk, Dov Kadmon, Timothy C. Thompson

    MOLECULAR THERAPY   13   S106 - S106   2006年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:NATURE PUBLISHING GROUP  

    Web of Science

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  • Therapeutic activities of IL-12 gene-modified macrophages embedded in FloSeal (R) in a mouse model of residual prostate cancer

    KI Tabata, M Watanabe, K Naruishi, T Satoh, WH Tian, H Wang, EMA Fattah, G Yang, D Kadmon, TC Thompson

    JOURNAL OF UROLOGY   175 ( 4 )   90 - 90   2006年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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  • Dynamin 2 is involved in PS-dependent phagocytosis in rat Sertoli cells

    O. Hiroshi Yamada, ShunAI Li, Norihiro Kusumi, Masami Watanabe, Yuji Kashiwakura, Kazuhito Tomizawa, Hiromi Kumon, Kohji Takei

    CELL STRUCTURE AND FUNCTION   30   73 - 73   2005年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPAN SOC CELL BIOLOGY  

    Web of Science

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  • Localization of amphiphysin1 and dynamin2 in tubulobulbar complexes (TBC) formation and sperm release at Sertoli cells

    Norihiro Kusumi, Masami Watanabe, Hiroshi Yamada, Shun-Ai Li, Yuji Kashiwakura, Atsushi Nagai, Yasutomo Nasu, Hiromi Kumon, Pietro De Camilli, Kohji Takei

    CELL STRUCTURE AND FUNCTION   30   71 - 71   2005年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPAN SOC CELL BIOLOGY  

    Web of Science

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  • Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis.

    M Watanabe, A Nagai, N Kusumi, Y Nasu, H Kumon, Y Kashiwakura

    JOURNAL OF UROLOGY   173 ( 4 )   409 - 409   2005年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: Long-term maspin expression efficiently suppresses tumor growth.

    M Watanabe, Y Nasu, N Kusumi, A Nagai, H Kunion, Y Kashiwakura

    JOURNAL OF UROLOGY   173 ( 4 )   65 - 65   2005年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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  • 腹腔鏡下摘除術を施行した副腎骨髄脂肪腫の2例

    坪井啓, 渡部昌実, 藤田治, 日下信行, 妹尾孝司, 雑賀隆史, 永井敦, 那須保友, 公文裕巳

    西日本泌尿器科   67   562 - 567   2005年

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  • エンドサイトーシス関連タンパク質amphiphysin 1の精巣における機能

    久住倫宏, 渡部昌実, 坪井啓, 永井敦, 公文裕巳, 山田浩司, 竹居孝二, 柏倉祐司

    日本泌尿器科学会雑誌   96 ( 2 )   2005年

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  • Dynamin 2 is involved in PS-dependent formation of membrane ruffles and phagocytosis in rat sertoli cells

    H Yamada, S Li, M Watanabe, F Wei, N Kusumi, K Tomizawa, M McNiven, H Matsui, H Kumon, K Takei

    MOLECULAR BIOLOGY OF THE CELL   15   195A - 196A   2004年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • PGE1陰茎海綿体自己注射に関する自主臨床研究中に妊娠に至った脊髄損傷患者の1例

    永井敦, 渡部昌実, 久住倫宏, 坪井啓, 公文裕巳

    日本性機能学会雑誌   19   243 - 245   2004年

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  • 岡山大学における性同一性障害患者(GID-FTM)に対するホルモン治療

    永井敦, 渡部昌実, 久住倫宏, 坪井啓, 公文裕巳

    日本性科学会雑誌   22   16 - 20   2004年

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  • 岡山大学医学部ジェンダークリニックにおける性同一性障害患者415名の解析

    永井敦, 久住倫宏, 渡部昌実, 坪井啓, 公文裕巳, 中塚幹也, 平松祐司, 難波祐三郎, 木股敬裕, 佐藤俊樹, 黒田重利

    日本小児泌尿器科学会雑誌   13   132 - 136   2004年

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  • 腎盂尿管癌術後の予後および膀胱癌発生に影響する因子の検討

    渡部昌実, 林俊秀, 高松正武, 紙谷章弘, 井上雅, 森末浩一, 入江伸, 金重哲三

    日本泌尿器科学会雑誌   94 ( 3 )   428 - 433   2003年

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  • 岡山大学におけるPGE1陰茎海綿体自己注射に対する自主臨床研究の取り組み

    永井敦, 渡部昌実, 久住倫宏, 公文裕巳

    日本性機能学会雑誌   18   247 - 252   2003年

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  • Expression of endocytic proteins in the testis, and their implication in spermatogenesis.

    A Kamitani, M Watanabe, H Iguchi, A Nagai, H Yamada, M Kinuta, K Takei, H Kumon

    JOURNAL OF UROLOGY   167 ( 4 )   319 - 319   2002年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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  • ラット培養セルトリ細胞におけるDynamin2,3の発現

    山田浩司, 紙谷章弘, 渡部昌実, 絹田正裕, 公文裕巳, 竹居孝二

    生化学   74 ( 8 )   2002年

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  • Multiple parallel plicationを行った先天性陰茎弯曲症の2例

    井口裕樹, 永井敦, 紙谷章弘, 渡部昌実, 公文裕巳

    日本性機能学会雑誌   16   43 - 47   2001年

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  • 岡山大学泌尿器科性機能外来におけるクエン酸シルデナフィル処方の経験

    井口裕樹, 永井敦, 紙谷章弘, 渡部昌実, 公文裕巳

    日本性機能学会雑誌   16   33 - 38   2001年

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  • ラット培養セルトリ細胞におけるエンドサイトーシス関連蛋白質の発現

    紙谷章弘, 山田浩司, 渡部昌実, 絹田正裕, 公文裕巳, 竹居孝二

    日本細胞生物学会大会講演要旨集   54th   2001年

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  • Vesicle formation and membrane lipid kinetics in model synaptic endocytosis using liposomes.

    M Kinuta, H Yamada, T Abe, M Watanabe, J Ohta, K Takei

    MOLECULAR BIOLOGY OF THE CELL   11   326A - 326A   2000年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

    Web of Science

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  • 岡山大学医学部附属病院泌尿器科性機能外来におけるシルデナフィル処方の現状

    永井敦, 井口裕樹, 渡部昌実, 公文裕巳

    日本性科学会雑誌   18 ( 1 )   9 - 13   2000年

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  • 神経終末タンパク質Amphiphysin Iのヒト精巣における発現

    渡部昌実

    日本不妊学会雑誌   45   119 - 125   2000年

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  • 細胞膜のダイナミックス エンドサイトーシスにおける細胞膜脂質の動態

    竹居孝二, 絹田正裕, 阿部匡史, 山田浩司, 太田潤, 渡部昌実

    日本細胞生物学会大会講演要旨集   53rd   2000年

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  • リポソームを用いたエンドサイトーシスのモデル実験と膜脂質の動態

    絹田正裕, 阿部匡史, 山田浩司, 太田潤, 渡部昌実, ラタナクル ニシャ, 竹居孝二

    日本細胞生物学会大会講演要旨集   53rd   2000年

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  • 陰嚢内脂肪腫の1例

    黒川真輔, 大橋輝久, 近藤捷嘉, 渡部昌実, 国友忠義

    泌尿器外科   12   65 - 67   1999年

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  • 岡山大学医学部附属病院泌尿器科における新婚ED(勃起障害)の臨床的検討

    永井敦, 真鍋和史, 渡部昌実, 岡部浩典, 公文裕巳

    日本性科学会雑誌   17   24 - 29   1999年

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  • 虫垂炎による水腎症の1例

    渡部昌実, 黒川真輔, 大橋輝久, 近藤捷嘉, 内藤稔, 国友忠義

    泌尿器外科   11   1165 - 1167   1998年

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  • SRYを有するXX maleの2例

    秋山道之進, 永井敦, 真鍋和史, 渡部昌実, 大森弘之

    西日本泌尿器科   60   421 - 423   1998年

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  • 経尿道的精阜切除術により妊娠成立をみた射精管嚢胞の1例

    秋山道之進, 永井敦, 渡部昌実, 真鍋和史, 津島知靖, 公文裕巳, 大森弘之

    西日本泌尿器科   60   477 - 480   1998年

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  • 最近の男子急性尿道炎症例の臨床的検討

    近藤捷嘉, 田村賢司, 渡部昌実, 黒川真輔, 大橋輝久

    岡山赤十字医誌   8   13 - 16   1997年

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  • 自然破裂をきたした腎血管筋脂肪腫の一例

    渡部昌実, 黒川真輔, 大橋輝久, 近藤捷嘉, 内藤稔, 名和清人, 国友忠義, 田口孝爾

    岡山赤十字医誌   8   62 - 65   1997年

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  • 糖尿病における排尿障害に関する検討

    大橋輝久, 岡部浩典, 渡部昌実, 黒川真輔, 近藤捷嘉, 松岡孝, 姫井孟

    岡山赤十字医誌   7   47 - 52   1996年

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▼全件表示

産業財産権

  • 液状薬剤浸透装置の補助装置及び液状薬剤浸透システム

    渡部 昌実, 定平 卓也

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    出願人:エースメディック株式会社

    出願番号:特願2020-046824  出願日:2020年3月17日

    公開番号:特開2021-145787  公開日:2021年9月27日

    J-GLOBAL

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  • 「下肢荷重位誘導装置」

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    出願番号:特願2018-225654  出願日:2018年11月30日

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  • 「REIC遺伝子を発現する制限増殖型アデノウイルス」

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    出願番号:PCT/JP2012/06425  出願日:2015年5月26日

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  • 「溶質および/または溶媒の局所での浸透および拡散を制御する装置、システム、および方法」

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    出願番号:特願2015-211828  出願日:2015年4月9日

    特許番号/登録番号:特許第6418645号 

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  • 「融合タンパク質を含む癌治療用医薬組成物」

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    出願番号:PCT/JP2013/053613  出願日:2013年2月15日

    特許番号/登録番号:特許第6124460号 

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  • 「REIC発現アデノウイルスベクター」

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    出願番号:PCT/JP2012/064250  出願日:2012年5月12日

    特許番号/登録番号:特許第6014029号 

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  • 「REIC/Dkk-3タンパク質の部分領域ポリペプチド」

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    出願番号:PCT/JP2011/065644  出願日:2011年7月1日

    特許番号/登録番号:特許第5936129号 

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  • 「遺伝子発現を上昇させるシステム及び該システムを保持したベクター」

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    出願番号:PCT/JP2010/071196  出願日:2010年11月19日

    特許番号/登録番号:特許第5697042号 

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  • 「特異的プロモーターの活性を上昇させるシステム及び該システムを保持したベクター」

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    出願番号:PCT/JP2010/056117  出願日:2010年3月30日

    特許番号/登録番号:特許第5733705号 

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  • 「単球から樹状細胞様分化を誘導し、抗癌免疫活性を高める癌の治療又は予防のための医薬組成物」

     詳細を見る

    出願番号::PCT/JP2009/056428  出願日:2009年

    特許番号/登録番号:特許第5447861号 

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  • 「新規悪性中皮腫治療剤及び免疫賦活化剤」

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    出願番号:PCT/JP2009/063907  出願日:2009年

    特許番号/登録番号:特許第5551593号 

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  • 「医薬組成物」

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    出願番号:特願2008-114729  出願日:2008年4月25日

    特許番号/登録番号:特許第5283962号 

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  • 「抗癌剤耐性癌において抗癌剤増強作用を有する癌細胞死誘導剤」

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    出願番号:特願2007-287373  出願日:2007年11月5日

    特許番号/登録番号:特許第5279235号 

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▼全件表示

受賞

  • 岡山大学泌尿器科学教室同門会, 第16回大森賞 受賞

    2014年  

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    受賞国:日本国

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  • 公益財団法人 武田科学振興財団 医学系研究奨励

    2013年  

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    受賞国:日本国

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  • 公益財団法人 前立腺研究財団研究助成 最優秀研究課題

    2012年  

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    受賞国:日本国

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  • 財団法人 両備てい園記念財団 研究助成「生物学に係る研究」受賞

    2010年  

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    受賞国:日本国

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  • 岡山大学泌尿器科学教室同門会, 第8回白雲会奨励賞 受賞

    2010年  

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    受賞国:日本国

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  • AKUA第10回泌尿器科研究助成 最優秀賞 受賞

    2010年  

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    受賞国:日本国

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  • 岡山医学会賞(山田賞)受賞

    2006年  

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    受賞国:日本国

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  • 岡山県医師会学術奨励賞 受賞

    2005年  

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    受賞国:日本国

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  • ヤングウロロジスト リサーチエッセイコンテスト, 優勝

    2005年  

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    受賞国:日本国

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  • 岡山大学泌尿器科学教室同門会, 第4回大森賞 受賞

    2002年  

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    受賞国:日本国

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  • 日本不妊学会学術奨励賞・オルガノン学術奨励賞 受賞

    2001年  

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    受賞国:日本国

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共同研究・競争的資金等の研究

  • 骨髄由来免疫抑制細胞の抗癌免疫逃避機構の解明に基づく革新的癌創薬の探索(分担)

    研究課題/領域番号:21K09371  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    黄 鵬, 渡部 昌実, 荒木 元朗, 植木 英雄

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • Zr-89標識イメージング技術に基づく次世代抗体医薬の創生プラットフォームの形成(分担)

    研究課題/領域番号:19KK0215  2019年10月 - 2023年03月

    日本学術振興会  科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(B))  国際共同研究加速基金(国際共同研究強化(B))

    佐々木 崇了, 樋口 隆弘, 渡部 昌実

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    配分額:18070000円 ( 直接経費:13900000円 、 間接経費:4170000円 )

    本研究はドイツーヴュルツブルグ大学におけるニ重特異性を有する次世代の人工抗体作成技術を導入し、本国研究組織におけるイメージング技術と融合することで、複数のがん抗原を同時に標的とした革新的な放射標識低分子抗体プローブを作成し、2種のがん抗原の重複を可視化することで、がん特異性を飛躍的に向上させたイメージング基盤技術の創出を目的とする。2019年度はニ重特異性抗体による高特異性・強調イメージング技術の検討として、高特異性・強調メージングプローブの開発のために、モデルとして多発性骨髄腫における表面抗原CD19およびCD20に対する人工抗体のPETプローブ化の準備及び検討を行った。トレーサー化のための分子設計をドイツにて行い、分子量の設定、重合体形成のためのリンカー構造の変更、低分子抗体の等電点などの最適化の検討を始めた。また日本ではプローブ化の検討として人工抗体の安定性と親和性の検討を開始した。

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  • 細胞骨格ダイナミクスに基づく分子輸送制御システムの解明と革新的癌創薬への新展開(代表)

    2019年04月 - 2024年03月

    科学研究費補助金【基盤研究(A)】 

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    資金種別:競争的資金

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  • 膀胱再生を目指した排尿平滑筋幹細胞の創出とその応用(分担)

    研究課題/領域番号:17K11184  2017年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    渡邉 豊彦, 渡部 昌実, 植木 英雄

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    国際禁制学会標準化委員会では,排尿筋低活動あるいは排尿筋無収縮のみ定義されており,低活動膀胱の定義は現在のところ確立されているものはない。排尿筋低活動は膀胱内圧尿流検査に基づいて「排尿筋収縮力の低下あるいは収縮時間の短縮で,排尿時間が延長したり,正常時間内に膀胱内の尿を完全に排出できない」と定義されているが,低活動膀胱は排尿筋障害に限定されるものではなく,求心性知覚神経,中枢神経,遠心性運動神経および排尿筋での障害が複合的に低活動膀胱に関与し,膀胱機能のいわば終末像とも言える。低活動膀胱の定義や診断基準が確立されていないため,正確な有病率は不明であるが,本邦での40歳以上の男女を対象とした疫学調査では,尿勢低下は男女ともに加齢とともに上昇し,尿流動態検査による検討では,排尿筋低活動は男性で40%前後,女性で15%前後に存在すると報告されている。このように低活動膀胱はその実態がいまだ明らかにされてはいないため,有効的な治療は存在せず,尿道カテーテルを留置されたまま放置されている患者も多い。このような状況の下,近年,本病態のメカニズムの解明,有効な治療法の確立へ向けた動きが活発となっている。
    我々の施設では従来より,臨床化へ向けた再生医学の基礎研究を進めてきたが,低活動膀胱に対する新しいアプローチとしての膀胱再生を目指した基礎研究もそのひとつである。本研究の目的は,膀胱収縮力獲得を目的とした尿路平滑筋細胞の創出,さらに得られた平滑筋細胞移植による膀胱再生である。具体的方法論は,組織特異的幹細胞分離法を用いて間葉系幹細胞,排尿平滑筋幹細胞を誘導・分離し,膀胱機能が荒廃した膀胱に移植することにより膀胱収縮,機能改善をはかることである。本年度は,排尿平滑筋幹細胞株樹立へ向けた基礎実験を行ない,間葉系幹細胞を用いた尿路平滑筋細胞分化への基礎的な実験を行なった。

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  • 腎組織幹細胞を用いた機能的腎小体の再生(代表)

    2016年04月 - 2019年03月

    科学研究費補助金【挑戦的萌芽研究】 

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    資金種別:競争的資金

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  • 前立腺癌における悪性形質およびアンドロゲン不応性の一元的制御機構の解明(代表)

    2015年04月 - 2019年03月

    科学研究費補助金【基盤研究(B)】 

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    資金種別:競争的資金

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  • 腎組織幹細胞における病的ストレス制御機構の解明(分担)

    2015年04月 - 2019年03月

    科学研究費補助金 

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    資金種別:競争的資金

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  • 癌増悪因子:CD147 Emmprinを標的とした新規の抗癌免疫療法の基盤の確立(分担)

    2015年 - 2018年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 転移先臓器を感知する受容体群の分子制御機構の解明とその応用(分担)

    2014年 - 2017年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 悪性胸膜中皮腫を対象とする遺伝子治療用医薬品(分担)

    2014年 - 2017年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 尿路平滑筋幹細胞の創出と尿道括約筋再生のための基盤的研究(分担)

    2014年 - 2017年

    科学研究費補助金 

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    資金種別:競争的資金

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  • Theranosticsを実現する89Zr標識による新規抗体・DDSキャリアの開発(分担)

    2014年 - 2016年

    科学研究費補助金 

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    資金種別:競争的資金

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  • アンドロゲン分泌性幹細胞の創出とその応用基盤の確立(分担)

    2013年 - 2017年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 腎組織幹細胞の誘導・分離に基づく腎再生研究基盤の確立(代表)

    2013年 - 2016年

    科学研究費補助金 

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    資金種別:競争的資金

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  • がん治療遺伝子REICによるナノバイオ標的医療の創成(分担)

    2013年 - 2015年

    科学研究費補助金 

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    資金種別:競争的資金

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  • REIC/Dkk-3の抗癌免疫活性に基づく次世代癌免疫療法の創成(代表)

    2013年 - 2015年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 新規の薬剤膜輸送制御機構の解明に基づく抗癌剤耐性克服治療薬の開発のための基盤研究(分担)

    2012年 - 2015年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 前立腺癌に対する次世代癌ワクチン化療法の開発研究(代表)

    2012年 - 2013年

    科学研究費補助金 

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    資金種別:競争的資金

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  • REIC/Dkk-3遺伝子治療による自己癌ワクチン化療法の基盤解析(分担)

    2011年 - 2014年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 難治性固形がん(悪性胸膜中皮腫、前立腺がん)に対する次世代自己がんワクチン化療法としてのREIC/Dkk-3遺伝子治療臨床研究(分担)

    2011年 - 2014年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 次世代自己がんワクチン化療法-第二世代REIC遺伝子発現アデノウイルス製剤の開発-(分担)

    2011年 - 2014年

    科学研究費補助金 

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    資金種別:競争的資金

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  • iPS細胞を用いた尿道括約筋機能再生のための基盤的研究(分担)

    2011年 - 2014年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 革新的分子イメージング技法を駆使するREIC遺伝子関連医薬の基盤開発(分担)

    2011年 - 2012年

    科学研究費補助金 

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    資金種別:競争的資金

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  • ガン細胞の走化浸潤を担うダイナミンナノクリップ;新たな制ガン剤の分子標的(分担)

    2010年 - 2013年

    科学研究費補助金 

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    資金種別:競争的資金

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  • がん治療遺伝子REICによるナノバイオ標的医療の創成(サブグループ:REIC遺伝子医薬の創製−遺伝子発現とキャリアシステムの開発−)(分担)

    2010年 - 2013年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 前立腺癌の臓器転移に及ぼす歯周感染病巣の影響に関する基礎的研究(分担)

    2010年 - 2013年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 緑色蛍光タンパク質発現ウイルス製剤による膀胱癌に対する新たな診断法の開発研究(分担)

    2010年 - 2013年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 表在性難治性膀胱癌に対する癌選択的膀胱注入治療薬の開発(代表)

    2010年 - 2012年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 新規の抗癌免疫活性化タンパク質「REIC」の前立腺癌における作用機序の解明(代表)

    2010年 - 2012年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 局所がん病巣を標的とする革新的生物製剤治療システムの開発(分担)

    2010年 - 2012年

    科学研究費補助金 

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    資金種別:競争的資金

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  • OMICにおける標的医療に向けた基盤技術の創成:抗体プローブの開発とその応用(サブグループ2:抗体・タンパク質抗原の大量発現系の確立)(分担)

    2010年 - 2012年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 基礎生物学およびこれに関係する臨床医学(遺伝子治療学、泌尿器科学)分野についての学術動向の調査研究(代表)

    2010年 - 2011年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 播種性癌細胞検出・分離のための新技術の開発(代表)

    2010年 - 2011年

    科学研究費補助金 

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    資金種別:競争的資金

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  • 癌特異的プロモーター活性を飛躍的に上昇させる改良型TSTAシステムの開発(代表)

    2009年 - 2010年

    科学研究費補助金 

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    資金種別:競争的資金

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  • エンドサイトーシスの分子メカニズムの解明(分担)

    2000年 - 2002年

    科学研究費補助金 

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担当授業科目

  • レギュラトリーサイエンス入門 (2021年度) 第4学期

  • 泌尿器病態学I(演習・実習) (2021年度) 特別  - その他

  • 泌尿器病態学I(講義・演習) (2021年度) 特別  - その他

  • 泌尿器病態学II(演習・実習) (2021年度) 特別  - その他

  • 泌尿器病態学II(講義・演習) (2021年度) 特別  - その他

  • 研究方法論基礎 (2021年度) 特別

  • 泌尿器病態学I(演習・実習) (2020年度) 特別  - その他

  • 泌尿器病態学I(講義・演習) (2020年度) 特別  - その他

  • 泌尿器病態学II(演習・実習) (2020年度) 特別  - その他

  • 泌尿器病態学II(講義・演習) (2020年度) 特別  - その他

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