研究者詳細 - 那須　保友

生体腎移植レシピエントにおける予防的抗菌薬と周術期感染症に関する後ろ向き調査

和田耕一郎, 荒木元朗, 西村慎吾, 山下里美, 河村香澄, 光井洋介, 吉岡貴史, 有吉勇一, 小林泰之, 渡邉豊彦, 北川正史, 田邊克幸, 杉山斉, 和田淳, 那須保友

移植 52 ( 総会臨時 ) 467 - 467 2017年8月

岡山大学病院における鏡視下ドナー腎採取術の検討

西村慎吾, 荒木元朗, 小林泰之, 山下里美, 河村香澄, 光井洋介, 吉岡貴史, 有吉勇一, 和田耕一郎, 渡辺豊彦, 那須保友

移植 52 ( 総会臨時 ) 422 - 422 2017年8月

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

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

Successful microscopic renal autotransplantation for left renal aneurysm associated with segmental arterial mediolysis 国際誌

Yoshioka T, Araki M, Ariyoshi Y, Wada K, Tanaka N, Nasu Y

Journal of Vascular Surgery 66 ( 1 ) 261 - 264 2017年7月

Tracking and Imaging of Tumor Progression and Immune Function in a Preclinical Mouse Model

Peng Huang, Naijin Xu, Eiji Matsuura, Masami Watanbe, Hiromi Kumon, Yasutomo Nasu, Chunxiao Liu

MOLECULAR THERAPY 25 ( 5 ) 98 - 98 2017年5月

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

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

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

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

A Combination Therapy of Partial Nephrectomy and Cryoablation Achieved Good Cancer Control and Renal Function in Bilateral Synchronous Renal Cell Carcinoma 査読

Atsushi Takamoto, Motoo Araki, Koichiro Wada, Morito Sugimoto, Yasuyuki Kobayashi, Katsumi Sasaki, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 71 ( 2 ) 187 - 190 2017年4月

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 report the case of a 58-year-old Japanese man with bilateral synchronous renal cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69 mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic embolization was performed for the left tumor, and 1 month later, a right open partial nephrectomy was performed. No recurrence was observed during a 16-month follow-up, and the serum creatinine level has been stable. The prognosis of bilateral synchronous RCC is better than that of dialysis patients. The novel approach of combining cryoablation and partial nephrectomy can achieve good cancer control and renal function in bilateral RCC.

DOI： 10.18926/AMO/54989

Evaluation of urinary stone composition and differentiation between urinary stones and phleboliths using single-source dual-energy computed tomography

Ogawa N, Sato S, Ida K, Kato K, Ariyoshi Y, Wada K, Nasu Y, Kanazawa S

Acta Med. Okayama 71 ( 2 ) 91 - 96 2017年4月

Impact of Surgeon and Hospital Volume on the Safety of Robot-Assisted Radical Prostatectomy: A Multi-Institutional Study Based on a National Database

Yosuke Hirasawa, Kunihiko Yoshioka, Yasutomo Nasu, Masumi Yamamoto, Shiro Hinotsu, Atsushi Takenaka, Masato Fujisawa, Ryoichi Shiroki, Keiichi Tozawa, Satoshi Fukasawa, Akira Kashiwagi, Katsunori Tatsugami, Masaaki Tachibana, Toshiro Terachi, Momokazu Gotoh

Urologia Internationalis 98 ( 3 ) 334 - 342 2017年4月

掲載種別：研究論文（学術雑誌）

© 2017 S. Karger AG, Basel. Introduction: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP). Materials and Methods: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra-A nd perioperative complications were collected. Results: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors. Conclusions: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP.

DOI： 10.1159/000460304

Scopus

ロボット手術の最前線

荒木元朗, 小林泰之, 和田耕一郎, 渡辺豊彦, 那須保友

IVR: Interventional Radiology 32 ( Suppl. ) 101 - 101 2017年4月

岡山大学病院におけるロボット支援腎部分切除術の経験

小林泰之, 荒木元朗, 谷本竜太, 西村慎吾, 高本篤, 堀川雄平, 和田耕一郎, 杉本盛人, 佐々木克己, 渡邊豊彦, 那須保友

日本泌尿器科学会総会 105回 SKH12 - 3 2017年4月

BENEFICAL EFFECT OF HYDROGEN SULFIDE ON RENAL ISCHEMIA-REPERFUSION INJURY IN CLAWN MINIATURE SWINE

Yuichi Ariyoshi, Mitsuhiro Sekijima, Takahiro Murokawa, Hisashi Sahara, Motoo Araki, Yasutomo Nasu, Kazuhiko Yamada

JOURNAL OF UROLOGY 197 ( 4 ) E77 - E78 2017年4月

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

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

Reality of nerve sparing and surgical margins in surgeons' early experience with robot-assisted radical prostatectomy in Japan

Tatsugami K, Yoshioka K, Shiroki R, Eto M, Yoshino Y, Tozawa K, Fukasawa S, Fujisawa M, Takenaka A, Nasu Y, Kashiwagi A, Gotoh M, Terachi T

Int J Urol 24 ( 3 ) 191 - 196 2017年3月

Interfractional Seminal Vesicle Motion Relative to the Prostate Gland for Image-guided Radiotherapy for Prostate Cancer with/without Androgen Deprivation Therapy: A Retrospective Cohort Study 査読

Takahiro Waki, Kuniaki Katsui, Toshiharu Mitsuhashi, Takeshi Ogata, Norihisa Katayama, Mitsuhiro Takemoto, Yasutomo Nasu, Hiromi Kumon, Susumu Kanazawa

ACTA MEDICA OKAYAMA 71 ( 1 ) 31 - 39 2017年2月

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 differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs' length and motion by computed tomography (CT) to determine the ADT's effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients' SV length was significantly shorter than the non-ADT patients'. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.111.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and nonADT patients in terms of interfractional motion of the SV tips and the SVs' center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used.

DOI： 10.18926/AMO/54823

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, Koichiro Wada, Motoo Araki, Ayano Ishii, Atsushi Takamoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 72 ( 2 ) 529 - 534 2017年2月

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 UNIV 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, beta-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 59 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.

DOI： 10.1093/jac/dkw424

The Prostate in Female? Clear Cell Adenocarcinoma in a Female Urethral Diverticulum 査読

Takuya Sadahira, Yuuki Maruyama, Motoo Araki, Yasuyuki Kobayashi, Toyohiko Watanabe, Yasutomo Nasu

UROLOGY 99 E25 - E26 2017年1月

記述言語：英語出版者・発行元：ELSEVIER SCIENCE INC

Urethral diverticular clear cell adenocarcinoma in a female patient is extremely rare. This tumor sometimes displays a characteristic image on magnetic resonance imaging, surrounding the urethra like the prostate does in men. We report a patient with this tumor who underwent cystourethrectomy and ileal conduit diversion. We think that imaging studies could be useful to make the appropriate diagnosis. UROLOGY 99: e25-e26, 2017. (C) 2016 Elsevier Inc.

DOI： 10.1016/j.urology.2016.10.021