研究等業績 - その他 - 成田　伸太郎

LOW PERCENTAGE (< 10%) OF POSITIVE BIOPSY CORE (PBC) IS NOT A PREDICTOR OF LOWER RISK FOR PSA RECURRENCE IN CT1C PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY IN CONTEMPORARY JAPANESE POPULATION

Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Shintaro Narita, Norihiko Tsuchiya, Koji Mitsuzuka, Sadafumi Kawamura, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  189 ( 4 ) E795 - E795   2013年04月

研究発表要旨（国際会議）  

PREDICTION OF PROGRESSION-FREE SURVIVAL IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR LOCALLY ADVANCED BLADDER CANCER USING A SNP PANEL OF CANCER-ASSOCIATED GENES

Takamitsu Inoue, Shigeyuki Matsui, Norihiko Tsuchiya, Kazuyuki Numakura, Susumu Akihama, Mitsuru Saito, Shintaro Narita, Shigeru Satoh, Wun-Jae Kim, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  189 ( 4 ) E379 - E380   2013年04月

研究発表要旨（国際会議）  

SINGLE POSITIVE BIOPSY AND PSA LEVEL < 10NG/ML WITH PROSTATE CANCER PATIENTS CAN NOT PREDICT UNILATERAL LESION IN RADICAL PROSTATECTOMY SPECIMENS IN CONTEMPORARY JAPANESE POPULATION

Takuya Koie, Koji Mitsuzuka, Takahiro Yoneyama, Shintaro Narita, Sadafumi Kawamura, Yuki Tobisawa, Tohru Yoneyama, Kazuyuki Mori, Akiko Okamoto, Hayato Yamamto, Atsushi Imai, Shingo Hatakeyma, Yasuhiro Hashimoto, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  189 ( 4 ) E791 - E792   2013年04月

研究発表要旨（国際会議）  

CYP3A5遺伝子多型に基づくグラセプタ個別投与による移植後早期の薬物動態と腎機能への影響

佐藤 滋, 沼倉 一幸, 斎藤 満, 井上 高光, 秋濱 晋, 成田 伸太郎, 土谷 順彦, 羽渕 友則, 加賀谷 英彰, 新岡 丈典, 三浦 昌朋

日本腎臓学会誌 ( (一社)日本腎臓学会 )  55 ( 3 ) 323 - 323   2013年04月

Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis.

Norihiko Tsuchiya, Shintaro Narita, Takamitsu Inoue, Mitsuru Saito, Kazuyuki Numakura, Mingguo Huang, Shingo Hatakeyama, Shigeru Satoh, Seiichi Saito, Chikara Ohyama, Yoichi Arai, Osamu Ogawa, Tomonori Habuchi

BMC cancer   13   150 - 150   2013年03月

BACKGROUND: The insulin-like growth factor-1 (IGF-1) plays an important role in growth of prostate cancer (PCa) cells and facilitating the development and progression of PCa. This study aimed to evaluate the association of polymorphisms in three linkage disequilibrium (LD) blocks of the IGF-1 on the survival of metastatic PCa patients. METHODS: A total of 215 patients with bone metastases at initial presentation were included in this study. The cytosine-adenine (CA) repeat polymorphism and rs12423791 were selected as representative polymorphisms in the LD blocks 1 and 2, respectively. Haplotype in the LD block 3 was analyzed using two tag single nucleotide polymorphisms (SNPs), rs6220 and rs7136446. Cancer-specific survival rate was estimated from the Kaplan-Meier curve, and the survival data were compared using the log-rank test. RESULTS: Cancer-specific survival was significantly associated with the CA repeat polymorphism, rs12423791, and rs6220 (P = 0.013, 0.014, and 0.014, respectively). Although rs7136446 had no significant association with survival, the haplotype in the LD block 3 was significantly associated with cancer-specific survival (P = 0.0003). When the sum of the risk genetic factors in each LD block (19-repeat allele, C allele of rs12423791, or C-T haplotype) was considered, patients with all the risk factors had significantly shorter cancer specific-survival than those with 0-2 risk factors (P = 0.0003). CONCLUSIONS: Polymorphisms in the IGF-1, especially a haplotype in the LD block 3, are assumed to be genetic markers predicting the outcome of metastatic PCa.

DOI PubMed

Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma.

Norihiko Tsuchiya, Shintaro Narita, Takamitsu Inoue, Naoko Hasunuma, Kazuyuki Numakura, Yohei Horikawa, Shigeru Satoh, Takeshi Notoya, Naohito Fujishima, Shingo Hatakeyama, Chikara Ohyama, Tomonori Habuchi

Anti-cancer drugs   24 ( 3 ) 310 - 4   2013年03月

The aim of this study was to evaluate the clinical factors, drug-related genetic polymorphisms, and human leukocyte antigen (HLA) types to determine the association with sorafenib-induced high-grade skin rash (HGSR) in Japanese patients with advanced renal cell carcinoma (RCC). A total of 55 patients with advanced RCC treated with sorafenib were analyzed retrospectively. Of these, 33 patients were subjected to HLA typing and polymorphism analyses of CYP3A5, ABCB1, ABCC2, and UGT1A1, which are involved in the metabolism and membrane transport of sorafenib. Grade 3 or higher SR developed in 12 (22%), and a higher incidence was observed in female patients than in male patients (40 vs. 15%, P=0.046). The initial dose, initial dose per body weight, and initial dose per body surface area in patients with HGSR were significantly higher than those in patients without HGSR. Patients with the ABCC2 -24CC genotype were at a significantly higher risk of SR than those with the CT genotype (35 vs. 0%, P=0.032). HLA-A*24 was significantly associated with the occurrence of HGSR (P=0.049). Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.

DOI PubMed

高脂肪食摂取下の前立腺癌増殖におけるFatty Acid Synthase(FASN)の役割

黄 明国, 成田 伸太郎, 土谷 順彦, 井上 高光, 佐藤 滋, 佐々木 雄彦, 羽渕 友則

日本泌尿器科学会雑誌 ( (一社)日本泌尿器科学会 )  104 ( 2 ) 411 - 411   2013年03月

CYP3A5遺伝子多型に基づくグラセプタ個別投与による移植後早期の薬物動態と腎機能への影響

佐藤 滋, 新岡 丈典, 加賀谷 英彰, 沼倉 一幸, 斎藤 満, 井上 高光, 小峰 直樹, 秋濱 晋, 成田 伸太郎, 土谷 順彦, 羽渕 友則, 三浦 昌朋

日本泌尿器科学会雑誌 ( (一社)日本泌尿器科学会 )  104 ( 2 ) 242 - 242   2013年03月

進行性腎細胞癌患者におけるsunitinib薬物治療モニタリング

土谷 順彦, 藤山 信弘, 成田 伸太郎, 井上 高光, 齋藤 満, 沼倉 一幸, 秋濱 晋, 佐藤 滋, 三浦 昌朋, 羽渕 友則

日本泌尿器科学会雑誌 ( (一社)日本泌尿器科学会 )  104 ( 2 ) 240 - 240   2013年03月

Laparoendoscopic single-site plus one trocar donor nephrectomy using the GelPort: initial clinical experience.

Takamitsu Inoue, Norihiko Tsuchiya, Shintaro Narita, Mitsuru Saito, Shinya Maita, Kazuyuki Numakura, Takashi Obara, Hiroshi Tsuruta, Yohei Horikawa, Shigeru Satoh, Tomonori Habuchi

Urology   81 ( 2 ) 308 - 12   2013年02月

OBJECTIVE: To achieve better cosmesis, less invasiveness, and less morbidity in donor nephrectomy without using specialized instruments, which is usually required in the laparoendoscopic single-site (LESS) procedure, we performed laparoendoscopic plus one trocar donor nephrectomy (LEPODN). METHODS: From October 2010 to December 2011, 20 living renal transplantation donors underwent the LEPODN procedure. Their mean age, body mass index (BMI), and preoperative creatinine clearance were 55.7 years, 23.2, and 118.4 mg/min, respectively. The GelPort laparoscopic system was inserted through a 5-6 cm pararectal incision at the umbilicus level. A subcostal 5-mm right-hand working trocar was placed under the left costal arch. The graft kidney was extracted using a retrieval bag. A 5-mm diameter drain was placed via a right-hand working trocar. Operative data of LEPODN were retrospectively compared to those of standard laparoscopic donor nephrectomy (standard-LDN, n = 27) previously performed at our hospital. RESULTS: The procedure was technically successful in all 20 patients. The mean operative time in the LEPODN group was significantly shorter than that in the standard-LDN group (229.1 vs 249.8 minutes, P = .033). Mean blood loss and warm ischemic time in the LEPODN group were 39.4 mL and 272.4 seconds, respectively. The mean serum creatinine concentrations of the recipients 7 and 30 days after operation were 1.57 and 1.13 mg/dL, respectively. These results were not significantly different from those in the standard-LDN group. CONCLUSION: The LEPODN procedure was feasible and performed without specialized instruments by surgeons experienced in only standard laparoscopic nephrectomy.

DOI PubMed

Impact of body mass index on clinicopathologic outcome and biochemical recurrence after radical prostatectomy in 1,257 Japanese patients with prostate cancer

Shintaro Narita, Koji Mitsuzuka, Takahiro Yoneyama, Sadafumi Kawamura, Yoichi Arai, Chikara Ohyama, Tatsuo Tochigi, Takuhiro Yamaguchi, Tomonori Habuchi

JOURNAL OF CLINICAL ONCOLOGY ( AMER SOC CLINICAL ONCOLOGY )  31 ( 6 )   2013年02月

研究発表要旨（国際会議）  

A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease.

Ali Amin Al Olama, Zsofia Kote-Jarai, Fredrick R Schumacher, Fredrik Wiklund, Sonja I Berndt, Sara Benlloch, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, David J Hunter, Brian E Henderson, Michael J Thun, Michael Gaziano, Edward L Giovannucci, Afshan Siddiq, Ruth C Travis, David G Cox, Federico Canzian, Elio Riboli, Timothy J Key, Gerald Andriole, Demetrius Albanes, Richard B Hayes, Johanna Schleutker, Anssi Auvinen, Teuvo L J Tammela, Maren Weischer, Janet L Stanford, Elaine A Ostrander, Cezary Cybulski, Jan Lubinski, Stephen N Thibodeau, Daniel J Schaid, Karina D Sorensen, Jyotsna Batra, Judith A Clements, Suzanne Chambers, Joanne Aitken, Robert A Gardiner, Christiane Maier, Walther Vogel, Thilo Dörk, Hermann Brenner, Tomonori Habuchi, Sue Ingles, Esther M John, Joanne L Dickinson, Lisa Cannon-Albright, Manuel R Teixeira, Radka Kaneva, Hong-Wei Zhang, Yong-Jie Lu, Jong Y Park, Kathleen A Cooney, Kenneth R Muir, Daniel A Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Nadiya Mahmud, Michelle Guy, Koveela Govindasami, Lynne T O'Brien, Rosemary A Wilkinson, Amanda L Hall, Emma J Sawyer, Tokhir Dadaev, Jonathan Morrison, David P Dearnaley, Alan Horwich, Robert A Huddart, Vincent S Khoo, Christopher C Parker, Nicholas Van As, Christopher J Woodhouse, Alan Thompson, Tim Dudderidge, Chris Ogden, Colin S Cooper, Artitaya Lophatonanon, Melissa C Southey, John L Hopper, Dallas English, Jarmo Virtamo, Loic Le Marchand, Daniele Campa, Rudolf Kaaks, Sara Lindstrom, W Ryan Diver, Susan Gapstur, Meredith Yeager, Angela Cox, Mariana C Stern, Roman Corral, Markus Aly, William Isaacs, Jan Adolfsson, Jianfeng Xu, S Lilly Zheng, Tiina Wahlfors, Kimmo Taari, Paula Kujala, Peter Klarskov, Børge G Nordestgaard, M Andreas Røder, Ruth Frikke-Schmidt, Stig E Bojesen, Liesel M FitzGerald, Suzanne Kolb, Erika M Kwon, Danielle M Karyadi, Torben Falck Orntoft, Michael Borre, Antje Rinckleb, Manuel Luedeke, Kathleen Herkommer, Andreas Meyer, Jürgen Serth, James R Marthick, Briony Patterson, Dominika Wokolorczyk, Amanda Spurdle, Felicity Lose, Shannon K McDonnell, Amit D Joshi, Ahva Shahabi, Pedro Pinto, Joana Santos, Ana Ray, Thomas A Sellers, Hui-Yi Lin, Robert A Stephenson, Craig Teerlink, Heiko Muller, Dietrich Rothenbacher, Norihiko Tsuchiya, Shintaro Narita, Guang-Wen Cao, Chavdar Slavov, Vanio Mitev, Stephen Chanock, Henrik Gronberg, Christopher A Haiman, Peter Kraft, Douglas F Easton, Rosalind A Eeles

Human molecular genetics   22 ( 2 ) 408 - 15   2013年01月

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

DOI PubMed

Comparison of surgical stress in patients undergoing open versus laparoscopic radical prostatectomy by measuring perioperative serum cytokine levels.

Shintaro Narita, Norihiko Tsuchiya, Teruaki Kumazawa, Shinya Maita, Kazuyuki Numakura, Takashi Obara, Hiroshi Tsuruta, Mitsuru Saito, Takamitsu Inoue, Yohei Horikawa, Shigeru Satoh, Tomonori Habuchi

Journal of laparoendoscopic & advanced surgical techniques. Part A   23 ( 1 ) 33 - 7   2013年01月

PURPOSE: We evaluated the perioperative serum levels of inflammatory cytokines in patients with prostate cancer (PCa) treated with open or laparoscopic radical prostatectomy (RP) and assessed the surgical stress based on the cytokine levels in addition to conventional clinical stress markers after surgery. PATIENTS AND METHODS: One hundred sixty-five patients who received RP for clinically localized PCa were enrolled. Serum levels of interleukin (IL)-10, IL-6, tumor necrosis factor-α, IL-1β, IL-8, and IL-12p70 were quantitatively measured using a multiplex bead array at three time points (i.e., before the operation [pre-OP], immediately after the operation [post-OP], and on postoperative Day 1 [POD1]). The perioperative changes in serum stress markers, including cytokines, were compared between patients who underwent open and laparoscopic RP, and the predictors for high levels of postoperative cytokines were assessed. RESULTS: The median age and estimated blood loss were significantly lower in the laparoscopic RP group than in the open RP group (P=.003 and P<.01, respectively). In all patients, body temperature, white blood cell count, and serum IL-10 and IL-6 levels were significantly higher at post-OP and POD1 than at pre-OP. Patients who underwent laparoscopic RP had significantly lower levels of serum IL-10, IL-6, and IL-1β at post-OP and POD1 than those who underwent open RP. Multivariate regression analyses showed that the surgical group (open versus laparoscopic) was an independent influencing factor on the levels of serum IL-6 and IL-10 at POD1 (P=.031 and P<.004, respectively) among various clinical perioperative parameters. CONCLUSIONS: Several inflammatory cytokines, particularly IL-6 and IL-10, are potential surgical stress markers in patients with PCa treated with RP. Based on cytokine production, our data support the view that laparoscopic RP is less invasive than open RP.

DOI PubMed

Distinct cancer-specific survival in metastatic prostate cancer patients classified by a panel of single nucleotide polymorphisms of cancer-associated genes.

Norihiko Tsuchiya, Shigeyuki Matsui, Shintaro Narita, Tomomi Kamba, Koji Mitsuzuka, Shingo Hatakeyama, Yohei Horikawa, Takamitsu Inoue, Seiichi Saito, Chikara Ohyama, Yoich Arai, Osamu Ogawa, Tomonori Habuchi

Genes & cancer   4 ( 1-2 ) 54 - 60   2013年01月

Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. A total of 185 PCa patients with bone metastasis at the initial diagnosis were analyzed. Germline DNA in each patient was genotyped using a cancer SNP panel that contained 1,421 SNPs in 408 cancer-related genes. SNPs associated with survival were screened by a log-rank test. Fourteen SNPs in 6 genes, XRCC4, PMS1, GATA3, IL13, CASP8, and IGF1, were identified to have a statistically significant association with cancer-specific survival. The cancer-specific survival times of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 v. 2-3 v. 4-6 risk genotypes; P = 7.20 × 10(-8)). The high-risk group was independently associated with survival in a multivariate analysis that included conventional clinicopathological variables (P = 0.0060). We identified 14 candidate SNPs in 6 cancer-related genes, which were associated with poor survival in patients with metastatic PCa. A panel of SNPs may help predict the survival of those patients.

DOI PubMed

A high-fat diet enhances proliferation of prostate cancer cells and activates MCP-1/CCR2 signaling.

Mingguo Huang, Shintaro Narita, Kazuyuki Numakura, Hiroshi Tsuruta, Mitsuru Saito, Takamitsu Inoue, Yohei Horikawa, Norihiko Tsuchiya, Tomonori Habuchi

The Prostate   72 ( 16 ) 1779 - 88   2012年12月

BACKGROUND: Dietary patterns including high-fat diet (HFD) and high-carbohydrate diet (HCD) play an important role in prostate cancer progression. However, which of these diets have the greatest effect on tumor progression and its underlying mechanisms remains unclear. METHODS: We investigated the effects of different diets on prostate cancer cell growth and the relevant circulating factors including serum insulin, growth factors, and inflammatory cytokines using the in vivo and ex vivo model. RESULTS: The tumor growth of prostate cancer LNCaP xenograft was significantly higher in the HFD group than in the HCD and control diet (CD) groups (P = 0.01; HFD vs. HCD, P = 0.025; HFD vs. CD, P = 0.003). The mean level of the serum monocyte chemoattractant protein-1 (MCP-1) in the HFD group was significantly higher than that in the HCD and CD groups (P = 0.024; HFD vs. HCD, P = 0.033; HFD vs. CD, P = 0.001). The mRNA levels of CC chemokine receptor 2 (CCR2), which is an MCP-1 receptor, and the expression of activated Akt were the highest in the HFD group. Furthermore, serum from HFD-fed mice enhanced the proliferation of two PCa cells and CCR2 knockdown inhibited HFD-induced proliferation of LNCaP cells. CONCLUSIONS: An HFD enhanced prostate cancer cell growth more strongly than an HCD or CD. MCP-1/CCR2 signaling may be involved in an HFD-induced prostate cancer progression.

DOI PubMed

Comparison of pharmacokinetics and pharmacogenetics of once- and twice-daily tacrolimus in the early stage after renal transplantation.

Takenori Niioka, Shigeru Satoh, Hideaki Kagaya, Kazuyuki Numakura, Takamitsu Inoue, Mitsuru Saito, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Masatomo Miura

Transplantation   94 ( 10 ) 1013 - 9   2012年11月

BACKGROUND: This study investigated pharmacokinetic and pharmacogenetic differences between a modified-release once-daily formulation of tacrolimus (Tac-QD) and the original formulation requiring twice-daily intake (Tac-BID) in de novo renal transplant recipients. METHODS: Forty-seven and 25 patients who received Tac-BID and Tac-QD, respectively, were enrolled. The pharmacokinetics and CYP3A5 6986A>G and ABCB1 3435C>T pharmacogenetics of each formulation were analyzed on day 28 posttransplantation. RESULTS: The dose-adjusted trough level (C0) and area under the concentration-time curve (AUC0-24) of tacrolimus were approximately 25% lower for Tac-QD than Tac-BID. However, there was a good correlation between the AUC0-24 and C0 in the Tac-BID and Tac-QD groups (r=0.575, P<0.001; and r=0.638, P<0.001, respectively) and a similar coefficient in each regression equation. The dose-adjusted AUC0-24 was approximately 25% lower in carriers of the CYP3A*1 allele (CYP3A5 expressers), but not individuals with the CYP3A*3/*3 genotype (nonexpressers), for TAC-QD than Tac-BID. In the Tac-QD group, the interpatient variability for dose-adjusted parameters was small, and the interquatile ranges of dose-adjusted parameters differed between CYP3A5 expressers and nonexpressers and did not overlap. The ABCB1 polymorphism was not associated with any pharmacokinetic parameters of Tac-QD. CONCLUSIONS: C0-guided monitoring may lead to similar AUC0-24 values for both formulations. However, to maintain the same AUC0-24 value, a higher dose of Tac-QD than Tac-BID may be needed, especially for CYP3A5 expressers, in the early stage posttransplantation. The narrow interindividual variability of Tac-QD pharmacokinetics and its difference between CYP3A5 expressers and nonexpressers might contribute to a dosing strategy based on CYP3A5 genotype.

DOI PubMed

日本人前立腺癌患者における全摘術後のPSA再発および臨床病理学的因子とBMIの関係

成田 伸太郎, 三塚 浩二, 米山 高弘, 川村 貞文, 荒井 陽一, 大山 力, 栃木 達夫, 羽渕 友則

日本癌治療学会誌 ( (一社)日本癌治療学会 )  47 ( 3 ) 1942 - 1942   2012年10月

最近10年間における限局性前立腺癌の腫瘍学的特徴の変化 前立腺全摘1268例の解析

三塚 浩二, 成田 伸太郎, 古家 琢也, 栫井 成彦, 海法 康裕, 土谷 順彦, 米山 高広, 川村 貞文, 栃木 達夫, 羽渕 友則, 大山 力, 荒井 陽一

日本癌治療学会誌 ( (一社)日本癌治療学会 )  47 ( 3 ) 1954 - 1954   2012年10月

薬物治療モニタリングに向けた進行性腎細胞癌患者におけるsunitinibの薬物動態の検討

土谷 順彦, 藤山 信弘, 成田 伸太郎, 井上 高光, 沼倉 一幸, 秋濱 晋, 佐藤 滋, 三浦 昌朋, 羽渕 友則

日本癌治療学会誌 ( (一社)日本癌治療学会 )  47 ( 3 ) 1052 - 1052   2012年10月

LAPARO-ENDOSCOPIC SINGLE-SITE (LESS) DONOR NEPHRECTOMY USING GELPOINT (R): AN INITIAL CLINICAL EXPERIENCE

Takamitsu Inoue, Shintaro Narita, Kazuyuki Numakura, Susumu Akihama, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi

JOURNAL OF ENDOUROLOGY ( MARY ANN LIEBERT INC )  26   A64 - A65   2012年09月

研究発表要旨（国際会議）