研究等業績 - その他 - 成田　伸太郎

Laparoscopic Versus Retroperitoneoscopic Living Donor Nephrectomy: Comparison of Two Procedures Regarding Clinical Outcome and Complication Rate

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

AMERICAN JOURNAL OF TRANSPLANTATION ( WILEY-BLACKWELL PUBLISHING, INC )  9   441 - 441   2009年

研究発表要旨（国際会議）  

Transplantation into the Long-Term Defunctionalized Bladder: Is It Cause of Vesicoureteral Reflux to the Renal Graft?

Takamitsu Inoue, Mitsuru Saito, Shigeru Satoh, Yoshiko Miura, Teruaki Kumazawa, Shintaro Narita, Yohei Horikawa, Norihiko Tsuchiya, Tomonori Habuchi

AMERICAN JOURNAL OF TRANSPLANTATION ( WILEY-BLACKWELL PUBLISHING, INC )  9   520 - 521   2009年

研究発表要旨（国際会議）  

Where Is the Most Preferable Surgical Wound Site for Living Donor Nephrectomy? A Questionnaire Assessment

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

AMERICAN JOURNAL OF TRANSPLANTATION ( WILEY-BLACKWELL PUBLISHING, INC )  9   440 - 441   2009年

研究発表要旨（国際会議）  

Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer.

Norihiko Tsuchiya, Takamitsu Inoue, Shintaro Narita, Teruaki Kumazawa, Mitsuru Saito, Takashi Obara, Hiroshi Tsuruta, Yohei Horikawa, Takeshi Yuasa, Shigeru Satoh, Tomonori Habuchi

The Journal of urology   180 ( 6 ) 2389 - 95   2008年12月

PURPOSE: There is considerable interindividual diversity in the development of adverse reactions during chemotherapy for cancers. This diversity is suggested to be attributable to differences in the disposition of chemotherapeutic agents, which is modified by genetic polymorphisms. In this study we evaluated the possible association of polymorphisms of genes involved in the metabolism, detoxification and transport of the agents with adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin therapy. MATERIALS AND METHODS: A total of 40 patients with urothelial cancer who received methotrexate, vinblastine, doxorubicin and cisplatin or high dose methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy between 1996 and 2005 at Akita University Medical Center were included in this study. Four genetic polymorphisms (ABCB1, GSTP1, CYP3A5 and MTHFR) and clinical parameters were included in the analysis to determine whether there was any association with the grade of adverse reactions at the first cycle and the worst grade of each adverse reaction throughout the chemotherapy period. RESULTS: On multivariate analysis the CYP3A5 A6986G genotype *3/*3 (OR 8.205, 95% CI 1.616-41.667, p = 0.011) and smaller number of treatment cycles (OR 0.156, 95% CI 0.037-0.659, p = 0.011) were independent factors for leukocytopenia (grade 3 or greater) throughout the period of chemotherapy. The mean white blood cell count nadir in patients with genotype *3/*3 was significantly lower than that in those with the *1 allele (1,542 +/- 903 vs 2,431 +/- 973/mm(3), p = 0.009). CONCLUSIONS: The A6986G polymorphism of CYP3A5, which is involved in the metabolism of vinblastine and doxorubicin, might be a genetic predictor of the severity of leukocytopenia induced by chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin.

DOI PubMed

Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population.

Zhiyong Ma, Norihiko Tsuchiya, Takeshi Yuasa, Takamitsu Inoue, Teruaki Kumazawa, Shintaro Narita, Yohei Horikawa, Hiroshi Tsuruta, Takashi Obara, Mitsuru Saito, Shigeru Satoh, Osamu Ogawa, Tomonori Habuchi

International journal of cancer   123 ( 11 ) 2574 - 9   2008年12月

Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand-induced tyrosine kinase activity. The Glycine (Gly) to Arginine (Arg) polymorphism at codon 388 (Gly388Arg), which encodes an amino acid in the transmembrane part of the FGFR4 gene, was reported to be associated with an increased risk in some carcinomas. We investigated the association between the Gly388Arg polymorphism or the G or A polymorphism at intron 11 (rs2011077) of FGFR4, which was located 1,213 base pairs apart from the Gly388Arg polymorphism, and the risk of prostate cancer or benign prostate hyperplasia (BPH), and the prostate cancer disease status in Japanese men. Genotypes of Gly388Arg and rs2011077 polymorphisms of FGFR4 were determined in 492 patients with prostate cancer, 165 patients with BPH and 179 male controls. Regarding the Gly388Arg polymorphism, individuals with the ArgArg genotype had a 2.207- and 1.958-fold increased risk of prostate cancer and BPH, and a 1.804-fold increased risk of metastatic prostate cancer compared with those with the GlyGly genotype. Regarding the rs2011077 polymorphism, individuals with the GG genotype had a 6.260- and 3.033-fold increased risk of prostate cancer and BPH, and a 5.550-fold increased risk of metastatic prostate cancer compared with those with the AA genotype. Our results indicate that the FGFR4 Arg allele of the Gly388Arg polymorphism and the G allele of the rs2011077 polymorphism have a significant impact on the development of prostate cancer and BPH, and the progression of prostate cancer in a Japanese population.

DOI PubMed

Characterization of prostate cancer detected at repeat biopsy.

Takeshi Yuasa, Norihiko Tsuchiya, Teruaki Kumazawa, Takamitsu Inoue, Shintaro Narita, Mitsuru Saito, Yohei Horikawa, Shigeru Satoh, Tomonori Habuchi

BMC urology   8   14 - 14   2008年11月

BACKGROUND: The aim of this study was to investigate the characteristics of prostate cancer patients who were diagnosed at repeat biopsy and compare them to non-cancerous patients or patients who were diagnosed at initial biopsy. METHODS: We carried out a retrospective analysis of clinical and pathological data from 576 patients, which included data on the period of time from radical prostatectomy to biochemical failure. RESULTS: Cancer was diagnosed in 191 (33%) of 576 patients at initial biopsy and in 23 (18%) of 127 patients who underwent a repeat biopsy. Cut-off values of 0.80 and 0.30 for prostate specific antigen velocity (PSAV) and prostate specific antigen density (PSAD), respectively, were determined using ROC curve analysis. Based on these values, PSAV and PSAD were able to predict 94% (46 of 49) of negative repeat biopsies, indicating that these patients had undergone unnecessary repeat biopsies. Although the patients who were diagnosed at repeat biopsy had a higher rate of organ-confined tumor than those who were diagnosed at initial biopsy (73% and 44%, respectively; P = 0.041), there were no differences in the recurrence rate or the duration of biochemical failure-free survival between the two groups. CONCLUSION: PSAV and PSAD may be useful indicators of the results of repeat biopsies. Although prostate cancer that was diagnosed at repeat biopsy was associated with a more favorable pathological profile, it was not associated with a better outcome after radical prostatectomy.

DOI PubMed

[Combination therapy consisting of gemcitabine, docetaxel and carboplatin as a second-line chemotherapy for patients with MVAC-treated metastatic urothelial carcinoma].

Takamitsu Inoue, Takashi Obara, Mitsuru Saito, Teruaki Kumazawa, Shintaro Narita, Yohei Horikawa, Takeshi Yuasa, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi

Hinyokika kiyo. Acta urologica Japonica   54 ( 9 ) 581 - 5   2008年09月

From 2001 to 2006, 11 patients with MVAC-treated metastatic urothelial carcinoma received as a second-line therapy GDC therapy consisting of gemcitabine (1,000 mg/m2) on day land 8, docetaxel (80 mg/m2) on day 1 and carboplatin (AUC 5) on day 1 in each 21-day cycle. The 11 patients received a total of 42 cycles. The median progression-free survival and the median overall survival were 3 months (range 0-51) and 10 months (range 2-51), respectively. The median overall survival from diagnosis of the metastasis was 13.0 months (range 7-55). Complete response and partial response rates were 1/11 (9%) and 5/11 (45%), respectively. One- and two-year survival rates were 36 and 9%, respectively. Grade 3 or 4 hematologic toxicity included neutropenia (69.0%), thrombocytopenia (47.6%) and anemia (45.2%). Non-hematologic toxicity of grade 3 or 4 consisted mainly of diarrhea (23.8%) and anorexia (21.4%). GDC regimen as a second-line chemotherapy was effective in 54% of patients with MVAC-treated metastatic urothelial carcinoma, although the high incidence of hematologic toxicities and short period of progression-free survival remain to be major problems.

PubMed

GLI2 knockdown using an antisense oligonucleotide induces apoptosis and chemosensitizes cells to paclitaxel in androgen-independent prostate cancer.

Shintaro Narita, Alan So, Susan Ettinger, Norihiro Hayashi, Mototsugu Muramaki, Ladan Fazli, Youngsoo Kim, Martin E Gleave

Clinical cancer research : an official journal of the American Association for Cancer Research   14 ( 18 ) 5769 - 77   2008年09月

PURPOSE: GLI transcription factors mediate hedgehog signaling and have been implicated in several human malignancies, including prostate cancer. The objectives of this study were to characterize GLI2 expression levels in human prostate cancer cell lines and tissues to test the effect of antisense oligonucleotide (ASO) targeting GLI2 on androgen-independent (AI) prostate cancer cell lines. EXPERIMENTAL DESIGN: A tissue microarray was used to characterize differences in GLI2 expression in benign prostate hyperplasia, prostate cancer treated by neoadjuvant hormonal therapy and AI prostate cancer. The effects of GLI2 ASO on PC-3 cell growth and paclitaxel chemosensitivity were assessed in vitro and in vivo. Oligonucleotide spotted microarray analysis was used to determine alteration in GLI2 coregulated genes after ASO treatment. RESULTS: The expression of GLI2 was significantly higher in prostate cancer than in benign prostate hyperplasia, decreased after androgen ablation in a time-dependent fashion, but became highly expressed again in AI prostate cancer. GLI2 ASO treatment of PC-3 cells reduced GLI2 mRNA and protein levels in a dose-dependent manner. GLI2 knockdown increased PC-3 cell apoptotic rates and significantly decreased cell growth and modulated levels of apoptosis-related genes, such as Bcl2, Bcl-xL, and clusterin. GLI2 knockdown also changed levels of several cell cycle regulators, such as cyclin D1, p27, and PKC-eta. Systematic administration of GLI2 ASO in athymic mice significantly delayed PC-3 tumor progression and enhanced paclitaxel chemosensitivity. CONCLUSIONS: These findings suggest that increased levels of GLI2 correlates with AI progression and that GLI2 may be a therapeutic target in castrate-resistant prostate cancer.

DOI PubMed

A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer.

Naofumi Narita, Takeshi Yuasa, Norihiko Tsuchiya, Teruaki Kumazawa, Shintaro Narita, Takamitsu Inoue, Zhiyong Ma, Mitsuru Saito, Yohei Horikawa, Shigeru Satoh, Osamu Ogawa, Tomonori Habuchi

BMC cancer   8   224 - 224   2008年08月

BACKGROUND: The purpose of this study was to evaluate the role of osteoprotegerin gene (OPG) polymorphisms as genetic modifiers in the etiology of prostate cancer (PCa) and disease progression. METHODS: Three hundred and sixty one patients with PCa and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped. RESULTS: There was no significant difference in the genotype frequencies between PCa patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic PCa patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031). CONCLUSION: Progression of PCa may be influenced by an intrinsic genetic factor of the host's bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with PCa.

DOI PubMed

Prognostic significance of HIF-1alpha polymorphisms in transitional cell carcinoma of the bladder

Junichi Nadaoka, Yohei Horikawa, Mitsuru Saito, Teruaki Kumazawa, Takamitsu Inoue, Shintaro Narita, Takeshi Yuasa, Shigeru Satoh, Hiroyuki Nishiyama, Osamu Ogawa, Norihiko Tsuchiya, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  179 ( 4 ) 320 - 320   2008年04月

研究発表要旨（国際会議）  

Prognostic significance of HIF-1 alpha polymorphisms in transitional cell carcinoma of the bladder.

Junichi Nadaoka, Yohei Horikawa, Mitsuru Saito, Teruaki Kumazawa, Takamitsu Inoue, Shintaro Narita, Takeshi Yuasa, Shigeru Satoh, Hiroyuki Nishiyama, Osamu Ogawa, Norihiko Tsuchiya, Tomonori Habuchi

International journal of cancer   122 ( 6 ) 1297 - 302   2008年03月

Recently, two single nucleotide polymorphisms in the hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene, P582S and A588T, were shown to cause significantly higher transcriptional activity than the wild type. We investigated the association between the HIF-1 alpha polymorphisms and the incidence and progression of transitional cell carcinoma of the bladder, and the relationship between the polymorphisms and the tissue vascular endothelial growth factor (VEGF) level or microvessel density (MVD). A total of 219 patients with bladder cancer and 464 healthy native Japanese control subjects were enrolled. Tissue VEGF and HIF-1 alpha expression levels and the mean MVD were evaluated in 73 radical cystectomy specimens by immunohistochemistry. The HIF-1 alpha genotype did not significantly influence the incidence or disease status of bladder cancer. Among patients who underwent radical cystectomy, those with a variant allele had significantly worse disease-free survival (p = 0.001) and disease-specific survival (p = 0.006) than those without a variant allele. Multivariate analysis using a Cox proportional hazard model revealed that the presence of a variant allele was an independent predictor of disease-free survival (HR = 3.10, 95%CI = 1.38-6.99, p = 0.006). Although not statistically significant, the moderate/high expression levels of VEGF in tumor tissues were more frequently observed in patients with a HIF-1 alpha variant allele (11/13, 84.6%) than in those without (33/60, 55%, p = 0.063). The HIF-1 alpha polymorphisms may have a significant influence on the poor prognosis of the patients undergoing radical cystectomy for bladder cancer, while they seem to have no relation to the bladder cancer occurrence.

PubMed

Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis.

Shintaro Narita, Norihiko Tsuchiya, Mitsuru Saito, Takamitsu Inoue, Teruaki Kumazawa, Takeshi Yuasa, Akira Nakamura, Tomonori Habuchi

The Prostate   68 ( 3 ) 321 - 35   2008年02月

BACKGROUND: Several studies have suggested that a high fat diet (HFD) may be a risk factor of prostate cancer (PCa). As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD). METHODS: LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT-PCR experiments. As for insulin-like growth factor I receptor (IGF-IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens. RESULTS: Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P<0.001 and P=0.006, respectively). We found 64 up-regulated genes (0.19%) and 14 down-regulated genes (0.04%) with more than twofold differences in the HFD xenograft. IGF-IR, TNFRSF, and LPL showed striking differences in the quantitative RT-PCR experiment. Immunostaining further revealed marked enhanced IGF-IR expression in the HFD xenograft. In human PCa, the lowest IGF-IR immunoreactivity group tended to have the lowest body mass index in both normal and PCa epithelium. CONCLUSION: HFD induced remarkable up- and down-regulation of mRNA of a substantial number of genes. Furthermore, the IGF-I system may be involved in the HFD-associated enhanced progression of PCa.

DOI PubMed

APP-085 腎細胞癌患者におけるDNAの完全性(副腎腫瘍・腎腫瘍/マーカー・臨床,総会賞応募ポスター,第96回日本泌尿器科学会総会)

土谷 順彦, 熊澤 光明, 井上 高光, 成田 伸太郎, 齋藤 満, 堀川 洋平, 小原 崇, 湯浅 健, 佐藤 滋, 羽渕 友則

日本泌尿器科学会雑誌 ( 一般社団法人 日本泌尿器科学会 )  99 ( 2 ) 252 - 252   2008年

DOI

Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer.

Hisami Fukuda, Norihiko Tsuchiya, Shintaro Narita, Teruaki Kumazawa, Yohei Horikawa, Takamitsu Inoue, Mitsuru Saito, Takeshi Yuasa, Shinobu Matsuura, Shigeru Satoh, Osamu Ogawa, Tomonori Habuchi

Oncology reports   18 ( 5 ) 1155 - 63   2007年11月

Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, is suggested to play a crucial role in tumor neovascularization and is associated with tumor progression and metastasis in prostate cancer. This study evaluated the significance of the VEGF T-460C polymorphism in the risk and the progression of prostate cancer. In a case-control experiment, 270 patients with prostate cancer and 252 male controls were investigated to assess the association of the VEGF T-460C polymorphism with the risk of prostate cancer. Prostate-specific antigen (PSA) recurrence in 95 patients who underwent radical prostatectomy and survival in 99 patients with metastases at diagnosis were analyzed to evaluate the influence of the polymorphism in cancer progression. The CC and TC genotypes of the polymorphism were associated with significantly higher rates of PSA recurrence after radical prostatectomy than the TT genotype and were independent predictors of PSA recurrence (P=0.011) in a multivariate analysis. In contrast, metastatic prostate cancer patients with the TT genotype showed significantly worse survival as compared to the CC and TC genotypes. In a multivariate analysis, the TT genotype was an independent predictor of cancer-specific survival (P=0.006). The VEGF T-460C polymorphism may have a substantial impact on both PSA recurrence after radical prostatectomy and survival in advanced prostate cancer. The molecular mechanisms of the polymorphism on the differing status in prostate cancer should be elucidated in further studies.

PubMed

Lymphatic invasion is a prognostic factor for bladder cancer treated with radical cystectomy.

Yohei Horikawa, Teruaki Kumazawa, Shintaro Narita, Takamitsu Inoue, Takeshi Yuasa, Shinobu Matsuura, Hiroshi Nanjo, Shigeru Satoh, Norihiko Tsuchiya, Tomonori Habuchi

International journal of clinical oncology   12 ( 2 ) 131 - 6   2007年04月

BACKGROUND: We aimed to elucidate the significance of pathological prognostic factors in patients with bladder cancer treated with radical cystectomy and pelvic lymphadenectomy focusing on the association between lymphatic invasion and disease recurrence. METHODS: Ninety-one patients with ladder cancer who had undergone radical cystectomy were examined retrospectively. Clinicopathological findings and clinical outcomes were analyzed. Patients who received palliative cystectomy or neoadjuvant chemotherapy and patients who did not receive lymphadenectomy owing to a poor general condition or far advanced local disease status were excluded. RESULTS: Lymphatic invasion and lymph node involvement were present in 45.1% and 23.1% of patients, respectively. Multivariate analyses, using the Cox proportional hazards model, indicated that lymphatic invasion (hazard ratio [HR], 5.30; P = 0.007) and lymph node involvement (HR = 3.05; P = 0.016) were independent prognostic factors for disease-specific survival. Of the 91 patients, 29 (31.9%) had recurrent disease during the follow-up period. The rate of recurrence in patients with lymphatic invasion and without lymph node involvement was 50% (11/22), which was not significantly different from that in patients with both lymphatic invasion and lymph node involvement (73.7%; 14/19; P = 0.121), indicating a high risk of disease recurrence in patients with bladder cancer with lymphatic invasion even in the absence of the lymph node involvement. CONCLUSION: In patients with bladder cancer treated with radical cystectomy, lymphatic invasion is an independent prognostic factor for disease-specific and disease-free survival. Patients with lymphatic invasion have a high risk of disease recurrence after radical cystectomy even in the absence of lymph node involvement.

PubMed

Clinical implication of vascular endothelial growth factor (VEGF) T-460C polymorphism in the risk and progression of prostate cancer

Norihiko Tsuchiya, Hisami Fukuda, Shintaro Narita, Teruaki Kumazawa, Yohei Horikawa, Takamitsu Inoue, Mitsuru Saito, Takeshi Yuasa, Shinobu Matsuura, Shigeru Satoh, Osamu Ogawa, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  177 ( 4 ) 53 - 53   2007年04月

研究発表要旨（国際会議）  

Gene expression in response to high-fat feeding in human prostate cancer xenograft model

Shintaro Narita, Norihiko Tsuchiya, Mitsuru Saito, Takamitsu Inoue, Teruaki Kumazawa, Yohei Horikawa, Takeshi Yuasa, Shinobu Matsuura, Shigeru Satoh, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  177 ( 4 ) 48 - 48   2007年04月

研究発表要旨（国際会議）  

Identifying genetic polymorphisms which predict adverse effects of MVAC in patients with urothelial cancers

Norihiko Tsuchiya, Takamitsu Inoue, Shintaro Narita, Teruaki Kumazawa, Mitsuru Saito, Yohei Horikawa, Takeshi Yuasa, Shinobu Matsuura, Shigeru Satoh

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  177 ( 4 ) 81 - 81   2007年04月

研究発表要旨（国際会議）  

APP-024 前立腺癌の進展における Osteoprotegerin の役割(第95回日本泌尿器科学会総会)

成田 直史, 湯浅 健, 土谷 順彦, 熊澤 光明, 堀川 洋平, 成田 伸太郎, 齋藤 満, 井上 高光, 松浦 忍, 佐藤 滋, 羽渕 友則

日本泌尿器科学会雑誌 ( 一般社団法人 日本泌尿器科学会 )  98 ( 2 ) 252 - 252   2007年

DOI

PP-618 進行性前立腺癌の予後におけるhGH, IGF-IならびにIL-6遺伝子多型の関与(第95回日本泌尿器科学会総会)

土谷 順彦, 成田 伸太郎, 熊澤 光明, 井上 高光, 馬 智勇, 齋藤 満, 堀川 洋平, 湯浅 健, 松浦 忍, 佐藤 滋, 小川 修, 羽渕 友則

日本泌尿器科学会雑誌 ( 一般社団法人 日本泌尿器科学会 )  98 ( 2 ) 551 - 551   2007年

DOI