Faculty Profiles - NASU Yasutomo

Papers - NASU Yasutomo

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Retroperitoneal bronchogenic cyst: a rare incidentaloma discovered in a juvenile hypertensive patient. International journal

Tomohiro Terasaka, Fumio Otsuka, Kanako Ogura-Ochi, Tomoko Miyoshi, Kenichi Inagaki, Yasuyuki Kobayashi, Yasutomo Nasu, Hirofumi Makino

Hypertension research : official journal of the Japanese Society of Hypertension 37 ( 6 ) 595 - 7 2014.6

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

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 2014.5

Language：English Publishing type：Research paper (scientific journal) Publisher：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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岡山大学泌尿器科におけるpreemptive腎移植症例の検討

有吉勇一, 荒木元朗, 宗石理沙, 吉岡貴史, 和田耕一郎, 小林泰之, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 清水千聖, 赤木滋, 森永裕士, 田邊克幸, 北川正史, 杉山斉, 和田淳, 槇野博史

移植 49 ( 1 ) 167 - 167 2014.5

多発転移を伴ったXp11.2転座型腎癌の1例

有吉勇一, 江原伸, 小林泰之, 賀来春紀, 那須保友, 公文裕巳, 田中健大, 柳井広之, 黒田直人

泌尿器外科 27 ( 別冊号 ) 76 - 76 2014.5

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

Masami Watanabe, Yasutomo Nasu, Hiromi Kumon

ONCOLOGY LETTERS 7 ( 3 ) 595 - 601 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：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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A novel gene expression system strongly enhances the anticancer effects of a REIC/Dkk-3-encoding adenoviral vector Reviewed

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 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：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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Retroperitoneal bronchogenic cyst: a rare incidentaloma discovered in a juvenile hypertensive patient

Terasaka T, Otsuka F, Ogura-Ochi K, Miyoshi T, Inagaki K, Kobayashi Y, Nasu Y, Makino H

Hypertens Res 37 ( 6 ) 595 - 597 2014.3

A Rare Complication: Misdirection of an Indwelling Urethral Catheter into the Ureter Reviewed

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

ACTA MEDICA OKAYAMA 68 ( 1 ) 47 - 51 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/52144

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

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 ) 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：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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Other Link： http://orcid.org/0000-0003-1761-6314

Robot-Assisted Radical Prostatectomy: Modified Ultradissection Reduces pT2 Positive Surgical Margins on the Bladder Neck Reviewed

Motoo Araki, Wooju Jeong, Sung Yul Park, Young Hoon Lee, Yasutomo Nasu, Hiromi Kumon, Sung Joon Hong, Koon Ho Rha

ACTA MEDICA OKAYAMA 68 ( 1 ) 35 - 41 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The purpose of this study was to compare the positive surgical margin (PSM) rates of 2 techniques of robot-assisted radical prostatectomy (RARP) for pT2 (localized) prostate cancer. A retrospective analysis was conducted of 361 RARP cases, performed from May 2005 to September 2008 by a single surgeon (KHR) at our institution (Yonsei University College of Medicine). In the conventional technique, the bladder neck was transected first. In the modified ultradissection, the lateral border of the bladder neck was dissected and then the bladder neck was transected while the detrusor muscle of the bladder was well visualized. Perioperative characteristics and outcomes and PSM rates were analyzed retrospectively for pT2 patients (n = 217), focusing on a comparison of those undergoing conventional (n = 113) and modified ultradissection (n = 104) techniques. There was no difference between the conventional and modified ultradissection group in mean age, BMI, PSA, prostate volume, biopsy Gleason score, and D'Amico prognostic criteria distributions. The mean operative time was shorter (p < 0.001) and the estimated blood loss was less (p < 0.01) in the modified ultradissection group. The PSM rate for the bladder neck was significantly reduced by modified ultradissection, from 6.2% to 0% (p < 0.05). In conclusion, modified ultradissection reduces the PSM rate for the bladder neck.

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

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 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：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.

DOI： 10.1507/endocrj.EJ13-0203

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腹腔鏡下膀胱全摘除術における初期経験に関する報告

佐々木克己, 小林泰之, 倉橋寛明, 和田耕一郎, 杉本盛人, 荒木元朗, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

Japanese Journal of Endourology 26 ( 3 ) 299 - 299 2013.11

腎盂尿管移行部狭窄症に対するAnderson-Hynes法によるロボット支援腹腔鏡下腎盂形成術

小林泰之, 荒木元朗, 倉橋寛明, 和田耕一郎, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

Japanese Journal of Endourology 26 ( 3 ) 227 - 227 2013.11

限局性前立腺癌における治療法別PSA非再発生存期間の検討、過去10年間での治療成績

高本篤, 谷本竜太, 小林泰之, 江原伸, 那須保友, 公文裕己

日本癌治療学会誌 48 ( 3 ) 1095 - 1095 2013.9

尿路上皮癌に対する術後補助療法としてのGCP療法

小林泰之, 谷本竜太, 江原伸, 那須保友, 公文裕巳

日本癌治療学会誌 48 ( 3 ) 2468 - 2468 2013.9

Predictive factors for acute and late urinary toxicity after permanent interstitial brachytherapy in Japanese patients

KANIMOTO Ryuta, BEKKU Kensuke, KATAYAMA Norihisa, KOBAYASHI Yasuyuki, EBARA Shin, ARAKI Motoo, TAKEMOTO Mitsuhiro, YANAI Hiroyuki, NASU Yasutomo, KUMON Hiromi

20 ( 8 ) 812 - 817 2013.8

岡山大学泌尿器科における腎移植症例の検討

宗石理沙, 荒木元朗, 和田耕一郎, 有吉勇一, 吉岡貴史, 上松克利, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 清水千聖

移植 48 ( 総会臨時 ) 357 - 357 2013.8

拡張型心筋症を合併した生体腎移植の1例

有吉勇一, 荒木元朗, 宗石理沙, 吉岡貴史, 清水千聖, 和田耕一郎, 佐々木克己, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

移植 48 ( 総会臨時 ) 396 - 396 2013.8

Clinical significance of CD24 as a predictor of bladder cancer recurrence. Reviewed

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 96 - 100 2013.7

多発転移を伴ったXp11.2転座型腎癌の1例

有吉勇一, 江原伸, 小林泰之, 賀来春紀, 那須保友, 公文裕巳, 田中健大, 柳井広之, 黒田直人

腎癌研究会会報 ( 43 ) 49 - 49 2013.7

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Papers - NASU Yasutomo