研究者詳細 - 成田　伸太郎

Clinical effects of single nucleotide polymorphisms on drug-related genes in Japanese metastatic renal cell carcinoma patients treated with sunitinib.

Kazuyuki Numakura, Norihiko Tsuchiya, Hideaki Kagaya, Makoto Takahashi, Hiroshi Tsuruta, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, Takenori Niioka, Masatomo Miura, Tomonori Habuchi

Anti-cancer drugs 28 ( 1 ) 97 - 103 2017年01月

Although sunitinib is a well-established chemotherapeutic for metastatic renal cell carcinoma (mRCC), there are no robust markers that predict efficacy and toxicity. We analyzed the effect of single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics on clinical outcomes in Japanese patients with mRCC. We analyzed the effect of SNPs in genes involved in sunitinib pharmacokinetics on the clinical outcome in mRCC patients in a Japanese population. We evaluated seven SNPs in four candidate genes, the transport proteins ATP-binding cassette (ABC) B1 (rs1045642, rs1128503, rs2032582, and rs7779562) and ABCG2 (rs2231142), and the metabolic proteins cytochrome P450 (CYP) 3A4 (rs35599367) and CYP3A5 (rs776746) in 70 patients. No significant association was observed between the genotypes of each SNP and time to dose reduction, progression-free survival, overall survival, and best objective response. Meanwhile, the incidence of grade 2 or greater hypertension and hand-foot syndrome, and multiple adverse events (>3), was significantly higher in patients carrying the ABCB1 rs2032582 GG genotype [odds ratio (OR): 5.37, 95% confidence interval (CI) 1.02-14.63, P=0.035; OR: 3.17, 95% CI 1.06-9.52, P=0.036, OR: 3.35; 95% CI 1.14-9.84; P=0.025, respectively]. In conclusion, our data showed that the ABCB1 rs2032582 GG genotype was associated with individual adverse events' susceptibility among Japanese patients treated with sunitinib in routine clinical settings.

PubMed

Takuma Narita, Takuya Koie, Teppei Ookubo, Koji Mitsuzuka, Shintaro Narita, Hayato Yamamoto, Takamitsu Inoue, Shingo Hatakeyama, Sadafumi Kawamura, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama

Medical oncology (Northwood, London, England) 34 ( 1 ) 1 - 1 2017年01月

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of biochemical recurrence.

PubMed

Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production

Huang M.

Oncotarget ( Oncotarget ) 8 ( 67 ) 111780 - 111794 2017年

DOI

Narita S.

Surgical Laparoscopy, Endoscopy and Percutaneous Techniques ( Surgical Laparoscopy, Endoscopy and Percutaneous Techniques ) 27 ( 4 ) e69 - e73 2017年

DOI

【鏡視下腎摘出術の新展開】LESS/RPSドナー腎採取術の現況と展望

井上高光, 成田伸太郎, 齋藤満, 奈良健平, 神田壮平, 沼倉一幸, 佐藤滋, 羽渕友則

腎移植・血管外科 ( 腎移植・血管外科研究会 ) 29 ( 3 ) 144 - 152 2017年

本邦の生体ドナー腎採取術の9割以上は腹腔鏡下ドナー腎採取術(laparoscopic donor nephrectomy:LDN)で行われているが、近年、一部の施設で単孔式腹腔鏡手術(Laparoendoscopic single-site surgery:LESS)に代表されるreduced port surgery(RPS)を採用したLDNが推進されてきた。従来法のLDN(Std-LDN)より更に低侵襲性や整容性を高めることは、数少ない生体腎移植ドナー候補に対して提供手術に納得していただくために重要であると考えられる。一方、LDNは健康なボランティアに対する手術であるため、安全性と採取腎の良好な機能が絶対的な要件である。従って、LESS/RPSの術式においては低侵襲性、整容性を担保しつつ同時に安全性も担保するreduced port surgery(RPS)の考え方が重要であると考えられる。腎に対するLESSでは副腎など小さな臓器の場合と異なり、腎摘出に必要な約5cmの単孔ではストレート鉗子のみでの操作で比較的容易に術式の完遂が可能である。また採取対象の腎の大きさは、腫瘍性疾患と異なり、各ドナー間でのばらつきが少ないため、ドナー腎採取術はLESSの良い適応であると考えられる。本稿では、LESSドナー腎採取術(Laparoendoscopic single-site donor nephrectomy:LESSDN)およびRPSを採用したLDNについて、国内外の過去の文献および当科の取り組みを紹介し、今後を展望する。(著者抄録)

[A Case of Giant Prostate Carcinoma Effectively Treated with External-Beam Radiation Therapy].

Sohei Kanda, Shintaro Narita, Naoki Komine, Seiichi Kitajima, Misa Yamauchi, Akihiro Sugita, Yutaka Saito, Tomonori Habuchi

Hinyokika kiyo. Acta urologica Japonica 62 ( 12 ) 647 - 650 2016年12月

We present a case of gigantic prostate tumor in a patient with castration-resistant prostate cancer with successful local control by external-beam radiation therapy. A 71-year-old man was shown to have a prostate specific antigen (PSA)level of 24.5 ng/ml, Gleason 9, cT2N1M1a, prostate adenocarcinoma with an estimated prostate volume of 26.9 g. He achieved a PSA nadir at 4 months after the initial androgen deprivation therapy and was diagnosed with castration-resistant prostate cancer three years later. Eight months after the diagnosis of castration-resistant prostate cancer, he visited our hospital due to urinary retention. Abdominal computed tomography scan showed a gigantic prostatic mass occupying the whole pelvic cavity along with multiple lymph node, bone and liver metastases. The estimated volume of the prostate was 878 g. A tumor needle biopsy revealed a histological finding similar to the initial prostate biopsy which was adenocarcinoma with Gleason 9. He underwent external beam radiation therapy (60 Gy) to the prostate, which brought about excellent local control with a 96.7% shrinkage of tumor at 2 months after radiation therapy. He had no complaints of urinary symptoms and no need for urethral catheterization until he died of prostate cancer metastases.

DOI PubMed

Altered miRNA expression in high-fat diet-induced prostate cancer progression.

Taketoshi Nara, Shintaro Narita, Huang Mingguo, Toshiaki Yoshioka, Atsushi Koizumi, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi

Carcinogenesis 37 ( 12 ) 1129 - 1137 2016年12月

Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array. The differences in 10 candidate miRNAs were validated using quantitative RT-PCR. We focused on miR-130a because the expression levels were significantly lower in the three PCa cell lines in comparison with benign prostate PINT1B cells. PCa cells cultured in a medium containing HFD mouse serum were associated with significantly higher cell proliferation rates and lower miR-130a expression levels. Further, miR-130a modulated MET expression in PCa cells, and MET was overexpressed in in vitro and in vivo HFD-induced PCa progression models. Moreover, ectopic miR-130a downregulated AR in LNCaP cells and DICER1 in PC-3 and DU145 cells, respectively. In human tissues, as elucidated using laser capture microdissection, the mean miR-130a expression level in cancer epithelium was significantly lower than that in normal epithelium. Furthermore, cytoplasmic MET in PCa tissues was overexpressed in patients with higher body mass index. In conclusion, a substantial number of miRNAs was altered in HFD-induced PCa growth. Specifically, miR-130a was attenuated in HFD-induced PCa progression with MET overexpression. miRNAs thus have implications in the mechanism, prevention and treatment of HFD-induced PCa progression.

PubMed

Efficacy and safety of bladder hydrodistension for decreased bladder capacity induced by intravesical BCG therapy.

Kazuyuki Numakura, Norihiko Tsuchiya, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, Tomonori Habuchi

Scandinavian journal of urology 50 ( 6 ) 429 - 432 2016年12月

OBJECTIVE: Intravesical BCG therapy is widely used for the treatment of high-risk, non-muscle-invasive bladder cancer. Among various reported side-effects, decreased bladder capacity is a serious side-effect that significantly worsens patients' quality of life. This article reports the efficacy and safety of bladder hydrodistension (BHD) in six patients with seriously decreased bladder capacity caused by BCG treatment. METHODS: Six patients with low bladder capacity (<100 ml in voiding diaries) and complaint of grade 3 irritative symptoms were diagnosed with decreased bladder capacity and treated with BHD. Alleviation of symptoms was defined as medication being discontinued or reduced after BHD. RESULTS: Five patients were male and one was female, and the mean age was 67.7 years. The mean interval between the last transurethral resection and BCG therapy was 26.0 days. Before BHD, all patients had been treated with antibiotics, anticholinergics and non-steroidal anti-inflammatory drugs (NSAIDs). The median bladder capacity before treatment was 40 ml (range 30-100 ml), and the median capacity increased to 200 ml (175-250 ml) within 2 weeks following BHD therapy. Four patients stopped NSAID use and three patients stopped anticholinergic use. One patient needed total cystectomy for recurrent symptoms. With a median follow-up period of 32 months, the bladder capacity remained stable without symptomatic deterioration in the remaining five patients. There was neither tumor spread nor disseminated tuberculosis infection. CONCLUSIONS: BHD appears to be an effective treatment option in patients with severely decreased bladder capacity. Its efficacy and safety were acceptable.

PubMed

von Hippel-Lindau病に合併した腫瘍性病変に対するアキシチニブによる治療経験

関根悠哉, 成田伸太郎, 五十嵐龍馬, 奈良健平, 松田芳教, 沼倉一幸, 鶴田大, 前野淳, 齋藤満, 井上高光, 羽渕友則, 佐藤滋, 立木裕

泌尿器外科 ( 医学図書出版(株) ) 29 ( 12 ) 1794 - 1794 2016年12月

ロボット支援腹腔鏡下前立腺全摘除術(RALP)における神経温存が術後尿失禁に及ぼす影響

高山孝一朗, 沼倉一幸, 鶴田大, 前野淳, 齋藤満, 井上高光, 成田伸太郎, 羽渕友則

日本排尿機能学会誌 ( (一社)日本排尿機能学会 ) 27 ( 1 ) 267 - 267 2016年12月

前立腺癌に合併した巨大精嚢cystadenomaの1例

石田雅宣, 井上高光, 前野淳, 喜早祐介, 高山孝一朗, 小泉淳, 山本竜平, 沼倉一幸, 鶴田大, 齋藤満, 成田伸太郎, 羽渕友則, 佐藤滋

泌尿器外科 ( 医学図書出版(株) ) 29 ( 12 ) 1793 - 1794 2016年12月

単一施設における根治的前立腺全摘術3術式における断端陽性率と陽性部位の比較

小泉淳, 成田伸太郎, 沼倉一幸, 鶴田大, 前野淳, 齋藤満, 井上高光, 佐藤滋, 羽渕友則