Faculty Profiles - NASU Yasutomo

Papers - NASU Yasutomo

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早期前立腺がんの治療戦略前立腺癌に対する根治療法前立腺全摘除術or密封小線源療法単一施設における検討

枝村康平, 雑賀隆史, 上杉達也, 能勢宏幸, 小林泰之, 真鍋大輔, 小武家誠, 江原伸, 那須保友, 公文裕巳

日本癌治療学会誌 45 ( 2 ) 492 - 492 2010.9

岡山大学における低、中リスク限局性前立腺癌に対するI-125永久密封小線源療法の成績

岸本涼, 枝村康平, 能勢宏幸, 上杉達也, 小武家誠, 小林泰之, 賀来春紀, 雑賀隆史, 那須保友, 公文裕巳

日本癌治療学会誌 45 ( 2 ) 677 - 677 2010.9

進行尿路上皮癌に対する化学療法奏功例におけるSalvage Surgeryの臨床的意義

雑賀隆史, 別宮謙介, 岸本涼, 枝村康平, 小林泰之, 賀来春紀, 那須保友, 公文裕巳

日本癌治療学会誌 45 ( 2 ) 1045 - 1045 2010.9

Two instillations of epirubicin as prophylaxis for recurrence after transurethral resection of Ta and T1 transitional cell bladder cancer: a prospective, randomized controlled study Reviewed

Takashi Saika, Tomoyasu Tsushima, Yasutomo Nasu, Yoshiyuki Miyaji, Michihisa Saegusa, Katsuji Takeda, Hiromi Kumon

WORLD JOURNAL OF UROLOGY 28 ( 4 ) 413 - 418 2010.8

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

Although transurethral resection (TUR) is the standard treatment for non-muscle-invasive bladder tumors, 40-80% of tumors recur in spite of complete resection.
To evaluate the efficacy, dose effectiveness and safety of early short-duration intravesical instillation therapy using epirubicin (EPI) administered immediately after TUR and on the next day following TUR.
Between 1995 and 2001, 303 patients with Ta and T1 non-muscle-invasive bladder carcinoma were enrolled in this study. Patients were randomized into three groups. Group A patients were treated with two intravesical infusions of EPI 20 mg/40 ml saline immediately after TUR and within 24 h. Group B patients were treated with EPI 50 mg/100 ml on the same schedule as group A. Group C patients were treated by TUR alone as a control group. The primary endpoint was a duration to the first recurrence.
Of the 303 patients, 79 in Group A, 84 in Group B, and 77 in Group C could be evaluated for recurrence. Median follow-up was 44 months. Median recurrence-free survival durations for Groups A, B, and C were 24, 38, and 13 months, respectively. The difference between Groups B and C was statistically significant (p = 0.04). Adverse reactions related to instillation were observed in about 30% of the patients. These reactions included micturition pain and frequency. These toxicities were mild and transient.
Intravesical instillation of EPI 50 mg twice within 24 h after TUR was effective as prophylactic therapy for non-muscle-invasive bladder cancer with tolerable toxicity problems.

DOI： 10.1007/s00345-009-0502-1

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5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer. International journal

Motohide Uemura, Seijiro Honma, Suyoun Chung, Ryo Takata, Mutsuo Furihata, Kazuo Nishimura, Norio Nonomura, Yasutomo Nasu, Tsuneharu Miki, Taro Shuin, Tomoaki Fujioka, Akihiko Okuyama, Yusuke Nakamura, Hidewaki Nakagawa

Cancer science 101 ( 8 ) 1897 - 1904 2010.8

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

Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

DOI： 10.1111/j.1349-7006.2010.01620.x

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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 Reviewed

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 2010.7

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

DOI： 10.1038/cgt.2010.5

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A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer

Masanori Noguchi, Tatsuyuki Kakuma, Hirotsugu Uemura, Yasutomo Nasu, Hiromi Kumon, Yasuhiko Hirao, Fukuko Moriya, Shigetaka Suekane, Kei Matsuoka, Nobukazu Komatsu, Shigeki Shichijo, Akira Yamada, Kyogo Itoh

CANCER IMMUNOLOGY IMMUNOTHERAPY 59 ( 7 ) 1001 - 1009 2010.7

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

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

DOI： 10.1007/s00262-010-0822-4

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Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3 Reviewed

Ryuta Tanimoto, Masakiyo Sakaguchi, Fernando Abarzua, Ken Kataoka, Kaoru Kurose, Hitoshi Murata, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

INTERNATIONAL JOURNAL OF CANCER 126 ( 7 ) 1562 - 1569 2010.4

Language：English Publishing type：Research paper (scientific journal) Publisher：JOHN WILEY & SONS INC

We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad-REIC. First, we isolated resistant clones from a human prostate cancer cell line, PC3, after repeated exposure to Ad-REIC. Infection efficiency of the adenovirus vector and expression level of REIC/Dkk-3 in the resistant clones were similar to those in the parental PC3 cells. By screening for alteration in levels and functional status of proteins involved in Ad-REIC-induced apoptosis, we found that BiP/GRP78, an ER-residing chaperone protein, was expressed at higher levels consistently among resistant cells. Expression levels of BiP and rates of apoptosis induced by Ad-REIC were inversely correlated. Down-regulation of BiP with siRNA sensitized the resistant cells to Ad-REIC in vivo as well as in culture. These results indicate that BiP is a major determinant of resistance to Ad-REIC-induced apoptosis. Thus BiP is useful for diagnosis of inherent and acquired resistance of cancers and also as a target molecule to overcome resistance to the gene therapeutic Ad-REIC.

DOI： 10.1002/ijc.24764

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Frequent silencing of tumor suppressive MicroRNA-34b/c by aberrant methylation in malignant mesothelioma Reviewed

Takafumi Kubo, Shinichi Toyooka, Kazunori Tsukuda, Hiroaki Asano, Masakiyo Sakaguchi, Junichi Soh, Tsuyoshi Ueno, Hiromasa Yamamoto, Masaomi Yamane, Takahiro Oto, Yasutomo Nasu, Hideki Matsui, Nam Ho Huh, Shinichro Miyoshi

CANCER RESEARCH 70 2010.4

CLITORIAL BLOOD FLOW CHANGES AFTER SURGERY WITH TENSION-FREE VAGINAL MESH FOR PELVIC ORGAN PROLAPSE Reviewed

Watanabe Toyohiko, Inoue Miyabi, Ishii Ayano, Yamato Toyoko, Nose Hiroyuki, Uematsu Katsutoshi, Sasaki Katsumi, Araki Motoo, Uehara Shinya, Saika Takashi, Nasu Yasutomo, Kumon Hiromi

JOURNAL OF UROLOGY 183 ( 4 ) E583 2010.4

Prognostic Factors Influencing Survival after Nephroureterectomy for Transitional Cell Carcinoma of the Upper Urinary Tract Reviewed

Yasuyuki Kobayashi, Takashi Saika, Daisuke Manabe, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 64 ( 1 ) 27 - 31 2010.2

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

We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of cause-specific survival. The prognostic significance wits tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p < 0.0001), tumor grade (p = 0.0324), and venous invasion (p < 0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p = 0.0205). Venous invasion wits the only independent prognostic factor in pathologrically localized UUT-UC.

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PP-416 新しい遠隔操作装置を用いた超音波ドプラ排尿動態検査(発表・討論,第98回日本泌尿器科学会総会)

上松克利, 渡辺豊彦, 鬼武万由子, 太田尚子, 宗宮昌子, 佐々木克己, 能勢宏幸, 小澤秀夫, 矢吹孝之, 谷本圭司, 山内博明, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 101 ( 2 ) 472 - 472 2010

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

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 2009.12

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

DOI： 10.3892/ijmm_00000293

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

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 2009.12

Language：English Publishing type：Research paper (scientific journal) Publisher：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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腹腔鏡下尿膜管遺残摘出術の4例

荒木元朗, 雑賀隆史, 上原慎一, 那須保友, 小林泰之, 渡邊豊彦, 公文裕巳

日本内視鏡外科学会雑誌 14 ( 7 ) 344 - 344 2009.12

A comparison of proteomic profiles changes during 17beta-estradiol treatment in human prostate cancer PC-3 cell line. Reviewed

Chen J,Huang P, Kaku H, Zhang K, Watanabe M, Saika T, Nasu Y, Kumon H

Cancer Genomics Proteomics 2009.11

Overexpression of the potential kinase serine/threonine/tyrosine kinase 1 (STYK 1) in castration-resistant prostate cancer

CHUNG Suyoun, TAMURA Kenji, FURIHATA Mutsuo, UEMURA Motohide, DAIGO Yataro, NASU Yasutomo, MIKI Tsuneharu, SHUIN Taro, FUJIOKA Tomoaki, NAKAMURA Yusuke, NAKAGAWA Hidewaki

100 ( 11 ) 2109 - 2114 2009.11

CTガイド下RFAが困難であったVHL随伴腎癌に対する腹腔鏡補助下RFAの経験

上松克利, 雑賀隆史, 郷原秀夫, 三村秀文, 荒木元朗, 石井亜矢乃, 小林泰之, 那須保友, 金澤右, 公文裕巳

Japanese Journal of Endourology and ESWL 22 ( 3 ) 165 - 165 2009.11

陰茎原発epithelioid sarcomaに対し陰茎全摘除術後に尿道陰茎再建術行った1例

西村慎吾, 枝村康平, 小林泰之, アバラズア・フェルナンド, 石井和史, 雑賀隆史, 那須保友, 公文裕巳

西日本泌尿器科 71 ( 増刊 ) 132 - 132 2009.10

右心房・右心室への進展をみとめる血栓患者に対する根治的腎摘出術(Radical Nephrectomy for a patient with a thrombus extending into the right atrium and ventricle)

Fernando Abarzua, 小林泰之, 西村慎吾, 雑賀隆史, 那須保友, 公文裕巳

西日本泌尿器科 71 ( 増刊 ) 168 - 168 2009.10

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Papers - NASU Yasutomo