研究等業績 - 原著論文 - 羽渕 友則
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Clinical significance of polymorphism and expression of chromogranin a and endothelin-1 in prostate cancer.
Zhiyong Ma, Norihiko Tsuchiya, Takeshi Yuasa, Mingguo Huang, Takashi Obara, Shintaro Narita, Yohei Horikawa, Hiroshi Tsuruta, Mitsuru Saito, Shigeru Satoh, Osamu Ogawa, Tomonori Habuchi
The Journal of urology 184 ( 3 ) 1182 - 8 2010年09月
研究論文（学術雑誌）
PURPOSE: We investigated the clinical significance of chromogranin A and endothelin-1 polymorphism and expression in prostate cancer. MATERIALS AND METHODS: We analyzed 2 CHGA polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in DNA samples of 435 patients with prostate cancer and 316 age matched male controls. Chromogranin A and endothelin-1 expression was evaluated by immunohistochemistry in prostate specimens of 114 men with prostate cancer who underwent radical retropubic prostatectomy and in 27 with bladder cancer who underwent radical cystectomy and served as controls. RESULTS: For the CHGA Glu264Asp polymorphism men with the GG genotype were at 2.05 times higher risk for prostate cancer than men with the CC genotype (p = 0.014). In men with prostate cancer higher chromogranin A immunohistochemistry grade was associated with higher stage and higher Gleason score (p = 0.011 and 0.044, respectively). Multivariate analysis showed that chromogranin A immunohistochemistry grade was an independent variable for predicting biochemical failure after radical prostatectomy (p = 0.023). Higher endothelin-1 expression was observed in prostate cancers (p = 0.011), especially those with a higher Gleason score (p = 0.042). There was no significant relationship between chromogranin A polymorphisms, and chromogranin A and endothelin-1 expression. CONCLUSIONS: Polymorphism and expression of chromogranin A and endothelin-1 have clinical significance in prostate cancer. Chromogranin A expression was an independent predictor of biochemical failure after prostatectomy in patients with localized prostate cancer.
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Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and mycophenolic acid exposure parameters on day 28 after renal transplantation.
Hideaki Kagaya, Masatomo Miura, Mitsuru Saito, Tomonori Habuchi, Shigeru Satoh
Basic & clinical pharmacology & toxicology 107 ( 2 ) 631 - 6 2010年08月
研究論文（学術雑誌）
The risk of acute rejection in patients with higher exposure to mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), might be due to inosine 5'-monophosphate dehydrogenase (IMPDH) polymorphisms. The correlations with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28 post-transplantation were investigated in 82 Japanese recipients. Renal transplant recipients were given combination immunosuppressive therapy consisting of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12 hr at designated times. There were no significant differences in the incidence of subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure range (AUC > 60 microg x h/ml and C(0 )> or = 1.9 microg/ml), there was a significant difference in the incidence of subclinical acute rejection between IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1 rs2278294 genotype. In the higher daytime MPA exposure range, patients with the IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection. In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute rejection episode tends to be low and the administration of MMF was effective. The risk of subclinical acute rejection for recipients who cannot adapt in therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1 rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism as well as monitoring of MPA plasma concentration after transplantation might help to improve MMF therapy.
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Medical mushrooms used for biochemical failure after radical treatment for prostate cancer: an open-label study.
Koji Yoshimura, Toshiyuki Kamoto, Osamu Ogawa, Shigeyuki Matsui, Norihiko Tsuchiya, Harue Tada, Keiko Murata, Kenichi Yoshimura, Tomonori Habuchi, Masanori Fukushima
International journal of urology : official journal of the Japanese Urological Association 17 ( 6 ) 548 - 54 2010年06月
研究論文（学術雑誌）
OBJECTIVE: The aim of this study was to assess the efficacy and safety of two different types of medical mushrooms in patients with prostate cancer in Japan. METHODS: Patients with biochemical failure after radical treatment for non-metastasized prostate cancer were enrolled in this open-label study. For 6 months they ingested one of the two following supplements: Senseiro, containing extracts from the Agaricus blazei Murill mushroom; and Rokkaku Reishi, containing the Ganoderma lucidum mushroom. Levels of serum prostate-specific antigen (PSA) level and PSA doubling time were examined before and after study entry to assess the impact of these supplements on disease progression. The primary end-point of this study was partial response rate (50% or more decrease of serum PSA). Hormonal status, represented by serum testosterone levels, and toxicity were also assessed. RESULTS: A total of 51 patients were enrolled following radical prostatectomy. Forty-seven completed the protocol and could be assessed. Thirty-two patients received Senseiro and the remaining 15 received Rokkaku Reishi. No partial response in terms of PSA was observed. Alteration of PSA doubling time did not correlate with that of serum testosterone levels. Serious adverse effects were not observed. CONCLUSIONS: No significant anticancer effects were observed with the intake of these two medical mushrooms.
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Post-transplant lymphoproliferative disorder involving the ovary as an initial manifestation: a case report.
Takamitsu Inoue, Shigeru Satoh, Mitsuru Saito, Yohei Horikawa, Norihiko Tsuchiya, Tomonori Habuchi
Journal of medical case reports 4 184 - 184 2010年06月
研究論文（学術雑誌）
INTRODUCTION: Because the normal ovary is assumed to be devoid of lymphoid tissue, it is unusual for it to be an initial manifestation of malignant lymphoma. This case is the first report, to our knowledge, of post-transplant lymphoproliferative disorder involving the ovary as an initial manifestation. CASE PRESENTATION: Twenty-nine weeks after a living renal transplantation, a 38-year-old Japanese female, whose ethnic origin was Asian, presented with abdominal pain and a chronic high fever. Computed tomography revealed a right ovarian tumor and liver metastases. The patient underwent oophrectomy based on the clinical diagnosis of liver metastasis from the primary ovarian tumor. The pathological diagnosis was Epstein-Barr Virus-associated post-transplant lymphoproliferative disorder. While ovarian malignant lymphoma has a poor prognosis, complete remission of liver involvement in this case was achieved only with a reduction of immunosuppressants. CONCLUSION: Clinicians should remember that malignant lymphoma could initially involve the ovary, especially if the patient is immunosuppressed after transplantation therapy.
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Relationship between bone mineral density and androgen-deprivation therapy in Japanese prostate cancer patients.
Takeshi Yuasa, Shinya Maita, Norihiko Tsuchiya, Zhiyong Ma, Shintaro Narita, Yohei Horikawa, Shinya Yamamoto, Junji Yonese, Iwao Fukui, Shunji Takahashi, Kiyohiko Hatake, Tomonori Habuchi
Urology 75 ( 5 ) 1131 - 7 2010年05月
研究論文（学術雑誌）
OBJECTIVES: To examine Japanese patients who had received androgen-deprivation therapy (ADT) for longer periods, as it is known that ADT of patients with prostate cancer reduces their bone mineral density (BMD). However, our previous cross-sectional study revealed that short-term ADT (average, 23.5 months) does not significantly increase the prevalence of osteoporosis in Japanese patients. METHODS: The subjects consisted of 201 native Japanese patients with prostate cancer. They comprised 113 ADT-treated and 88 hormone-naive patients. Lumbar spine, total hip, and femoral neck BMDs were measured by dual-energy x-ray absorptiometry and expressed in standard deviation units relative to the scores of young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. RESULTS: The ADT-treated patients had significantly lower BMD values, T-scores, and even Z-scores than the hormone-naive patients (P <.001). For patients who were hormone-naive, ADT-treated for less than 2 years, and ADT-treated for more than 2 years, the osteoporosis prevalence was 4.5% (4/88), 12.1% (4/33), and 10.8% (4/37), respectively. The ADT-treated patients had significantly higher serum amino-terminal telopeptide levels than the hormone-naive patients (P = .014), but significantly lower serum carboxy-terminal telopeptide of type-I collagen levels than the ADT-treated patients with bone metastasis (P <.001). CONCLUSIONS: Our cross-sectional study confirmed that both ADT-treated and hormone-naive Japanese patients with prostate cancer have low rates of osteoporosis. These findings are different from those of studies in western countries. Genetic and hormonal or other environmental factors may result in population differences in the characteristics of prostate cancer and BMD.
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Current status and future issue of molecular targeted agents in solid tumors: Lessons learned from renal cell carcinoma
Norihiko Tsuchiya, Tomonori Habuchi
Drug Delivery System 25 ( 2 ) 134 - 142 2010年
研究論文（学術雑誌）
We are facing a dramatic shift from cytokine therapy to molecular targeted agents in the therapeutic strategy for advanced renal cell carcinoma. Molecular targeted agents used in renal cell carcinoma, tyrosin kinase inhibitors, mTOR inhibitors, and anti-VEGF antibody, inhibit tumor growth mainly though anti-angiogenic activity. Those agents have different profiles of adverse events and sometimes induce unexpected serious events, although having a strong anti-tumor growth. To ensure maximum therapeutic effect, a team approach involving multi-disciplinary staffs becomes more important than ever.
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Mass screening of prostate cancer and its impact on inhabitants in akita prefecture, Japan
T. Kato, T. Habuchi, N. Tsuchiya, K. Sato, S. Kitajima, S. Kato
Aktuelle Urologie 41 ( SUPPL. 1 ) 2010年
研究論文（学術雑誌）
In 2001, the Akita Medical Association started a prostate cancer (PC) mass screening project for ≥50-year-old male inhabitants in individual municipalities of Akita Prefecture, utilizing serum prostate-specific antigen. The number of examinees increased from 4321 in 2001 to 29936 in 2006, while the annual rate of examinees per target inhabitants remained at 11.6 to 16.8% and the fraction of repeat examinees increased up to 77% in 2006. A total of 944PCs were screened with a stageB tumor incidence of 84.1% (range: 82.2 to 86.6%). The annual PC detection rate was 0.95 to 1.11% for the first 4 years, but then declined to 0.54% in 2006 mainly due to the increase of repeat examinees. PSA mass screening is effective for the detection of early stage PC, but a further promotion is needed to mobilize the sleeping inhabitants. Indeed, the number of new PC patients in 17 major hospitals in Akita Prefecture rapidly increased after the mass screening started (3.2-fold), suggesting an enlightenment effect of the screening project on both the inhabitants and general physicians. © Georg Thieme Verlag KG.
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Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers
Habuchi T， et al
Cancer 2003年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect
Habuchi T， et al
Cancer Res. 2000年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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A novel candidate tumour suppressor locus at 9p32-33 in bladder cancer : localization of the candidate region in a single 840 kb YAC
Habuchi T， et al
Hum Mol Genet 1997年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Metachronous multifocal development of urothelial cancers by intraluminal seeding
Habuchi T， et al
Lancet 1993年01月 [査読有り]
研究論文（学術雑誌） 国内共著