研究者詳細 - 羽渕　友則

研究等業績 - その他 - 羽渕　友則

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Candidate genes involved in the defunctionalization and refunctionalization of the urinary bladder induced by bladder anuria and reperfusion

Kisou Y.

Neurourology and Urodynamics ( Neurourology and Urodynamics ) 39 ( 6 ) 1653 - 1666 2020年08月

AIMS: We develop a novel rabbit urinary diversion model of bladder defunctionalization due to bladder anuria followed by refunctionalization due to urine reperfusion to investigate the molecular biological background. To validate the results, we used reverse transcription-polymerase chain reaction (RT-PCR) to analyze human specimens from defunctionalized bladders in patients receiving dialysis before kidney transplantation. METHODS: Female rabbits were divided into three groups: control, defunctionalized, and refunctionalized. The bilateral ureters were anastomosed to vagina in the defunctionalized and refunctionalized groups at 0 weeks. In the refunctionalized group, the unilateral ureter was reanastomosed to the bladder at 8 weeks. RESULTS: The capacity and compliance of the rabbit bladder in the refunctionalized group were significantly lower than those in the control group at 8 weeks and higher than those in the defunctionalized group at 14 weeks. The significant downregulation of IGFBP2, UPK1B, and CST6 in the defunctionalized group compared with that in the control groups, and the significant downregulation of AGTR2 in the refunctionalized group compared with that in the defunctionalized group in the rabbit bladder-muscle DNA microarray were validated by RT-PCR. Human bladder muscle indicated significant downregulation of UPK1B and CST6 and significant downregulation of IGFBP2 in the defunctionalized group, which is consistent with both rabbit bladder-muscle DNA microarray and rabbit bladder RT-PCR results. CONCLUSIONS: The present study using novel model of bladder defunctionalization followed by refunctionalization indicated the consistent downregulation of UPK1B and CST6 in muscle and the consistent downregulation of IGFBP2 in mucosa in process of bladder defunctionalization, which was validated by human specimens.

DOI PubMed

Efficacy and safety of nivolumab for renal cell carcinoma in patients over 75 years old from multiple Japanese institutes

Numakura K.

International Journal of Clinical Oncology ( International Journal of Clinical Oncology ) 25 ( 8 ) 1543 - 1550 2020年08月

PURPOSE: Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab's efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. METHODS: From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups. RESULTS: The median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37-1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68-2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535). CONCLUSIONS: Nivolumab's effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.

DOI PubMed

LINC00992 contributes to the oncogenic phenotypes in prostate cancer via targeting miR-3935 and augmenting GOLM1 expression

Chen J.

BMC Cancer ( BMC Cancer ) 20 ( 1 ) 749 - 749 2020年08月

BACKGROUND: Accumulating evidence has revealed the critical role of long non-coding RNAs (lncRNAs) in cellular processes during tumor progression. As documented in cancer-related literatures, LINC00992 expression is associated with cancer progression, whereas its function in tumors including prostate cancer has not been characterized yet. METHODS: Data from GEPIA database suggested LINC00992 expression in prostate cancer tissues. The expression levels of RNAs were monitored via qRT-PCR. Western blot evaluated the levels of proteins. The proliferation, apoptosis and migration of prostate cancer cells were assessed by CCK-8, EdU, TUNEL, Transwell and wound healing assays. Luciferase reporter, RNA pull down and RIP assays were applied to detect the interplays among LINC00992, miR-3935 and GOLM1. RESULTS: Elevated levels of LINC00992 and GOLM1 were detected in prostate cancer tissues and cells. LINC00992 exerted facilitating functions in prostate cancer cell proliferation and migration. Mechanically, LINC00992 interacted with and negatively regulated miR-3935 to elevate GOLM1 expression in prostate cancer cells. In addition, the in vitro suppressive effect of silenced LINC00992 on prostate cancer cell proliferation and migration was reversed by GOLM1 upregulation. Likewise, LINC00992 depletion restrained tumor growth in vivo was offset by enhanced GOLM1 expression. CONCLUSIONS: LINC00992 competitively bound with miR-3935 to elevate GOLM1 expression and therefore facilitate the oncogenic phenotypes of prostate cancer cells, implying a potential LINC00992-targeted therapy for prostate cancer.

DOI PubMed

内分泌単独療法で開始したCHAARTED low-volume転移性前立腺癌における予後因子の検討

久木元隆, 成田伸太郎, 野村恭子, 畠山真吾, 高橋正博, 櫻井俊彦, 川村貞文, 星宣次, 石田雅宣, 石戸谷滋人, 下田次郎, 佐藤博美, 三塚浩二, 栃木達夫, 土谷順彦, 大山力, 荒井陽一, 羽渕友則

泌尿器外科 ( 医学図書出版(株) ) 33 ( 8 ) 1053 - 1056 2020年08月

本邦9施設で去勢単独療法による治療を開始した内分泌感受性転移性前立腺癌556例のうち、CHAARTED low-volumeに分類される184例の予後因子を後ろ向きに解析検討した。治療前因子の単変量解析でGleason score≧9、LDH高値、ヘモグロビン低値が無CRPC生存と全生存に有意に関連し、Gleason score≧9は独立した予後因子であった。経過中の予後関連因子の単変量解析ではPSA nadir≧0.2ng/mL、time to PSA nadir<6ヵ月が無CRPC生存と全生存に有意に関連した。治療経過中因子を含めた多変量解析ではGleason score≧9、TTN<6ヵ月、PSA nadir≧0.2ng/mLが独立した危険因子であった。(著者抄録)

内分泌単独療法で開始したCHAARTED low-volume転移性前立腺癌における予後因子の検討

泌尿器外科 ( 医学図書出版(株) ) 33 ( 8 ) 1053 - 1056 2020年08月

原発性アルドステロン症と副腎コルチゾール産生腺腫の合併例の臨床的検討

石田雅宣, 沼倉一幸, 小林瑞貴, 山本竜平, 小泉淳, 奈良健平, 神田壮平, 齋藤満, 成田伸太郎, 井上高光, 羽渕友則

日本内分泌外科学会雑誌 ( (一社)日本内分泌外科学会 ) 37 ( Suppl.1 ) S101 - S101 2020年08月

秋田大学医学部附属病院における初診時85歳以上の膀胱癌患者の治療成績

提箸隆一郎, 沼倉一幸, 山本竜平, 小泉淳, 奈良健平, 齋藤満, 井上高光, 成田伸太郎, 佐藤滋, 羽渕友則

日本老年泌尿器科学会誌 ( 日本老年泌尿器科学会 ) 33 ( 1 ) 136 - 136 2020年08月

Association of tumor burden with the eligibility of upfront intensification therapy in metastatic castration-sensitive prostate cancer: A multicenter retrospective study

Hatakeyama S.

International Journal of Urology ( International Journal of Urology ) 27 ( 7 ) 610 - 617 2020年07月

OBJECTIVES: To evaluate the association of tumor burden with the prognosis in real-world patients with metastatic castration-sensitive prostate cancer and to investigate the eligibility for upfront intensification therapy. METHODS: We retrospectively evaluated 679 patients with metastatic castration-sensitive prostate cancer who were initially treated with conventional androgen deprivation therapy between August 2001 and November 2018. The primary purpose was to investigate the eligibility for upfront intensification therapy based on the progression of metastatic castration-resistant prostate cancer. The secondary purpose included the comparison of the metastatic castration-resistant prostate cancer progression rate, metastatic castration-resistant prostate cancer-free survival and overall survival after castration-resistance in CHAARTED low- or high-volume disease patients. RESULTS: The number of patients with metastatic castration-resistant prostate cancer progression was 119 (52%) and 319 (71%) in the low- and high-volume disease groups, respectively. The metastatic castration-resistant prostate cancer progression rate (P < 0.001) and castration-resistant prostate cancer-free survival (P < 0.001) were significantly different between the low- and high-volume disease groups, but no difference was found for overall survival after castration resistance (P = 0.363). Multivariate Cox regression analysis showed no significant association between tumor burden and overall survival after castration resistance (P = 0.522; hazard ratio 1.14). CONCLUSIONS: The progression rate in metastatic castration-resistant prostate cancer patients with the low-volume disease under conventional androgen deprivation therapy is approximately 50%. Upfront intensification therapy might be beneficial for approximately half of patients with low-volume disease. A novel maker to predict the castration-resistant status is required to select optimal patients for upfront intensification therapy.

DOI PubMed

【オリゴ転移・オリゴ再発前立腺癌を巡る諸問題】原発巣標的局所治療

沼倉一幸, 成田伸太郎, 羽渕友則

泌尿器外科 ( 医学図書出版(株) ) 33 ( 7 ) 946 - 952 2020年07月

本総説では、オリゴ転移前立腺癌における原発巣を標的とした局所治療について解説する。オリゴ転移の定義などまだ議論がある部分については理解を助けるための最小限の記述にとどめ、新たな疾患概念ともいえるオリゴ転移前立腺癌に対する原発巣標的局所治療(放射線療法、腫瘍減量前立腺全摘除そして凍結療法)についてのエビデンスと実際の臨床への適応を考察した。オリゴ転移の定義などの詳細な説明は割愛したので該当する他項を参照していただきたい。(著者抄録)

【泌尿器がんのリンパ節転移とリンパ節郭清】ロボット支援腹腔鏡下前立腺全摘除術のリンパ節郭清

成田伸太郎, 羽渕友則

泌尿器科 ( (有)科学評論社 ) 12 ( 1 ) 67 - 70 2020年07月

Changes in PCSK9 and LDL cholesterol concentrations by everolimus treatment and their effects on polymorphisms in PCSK9 and mTORC1

Sato S.

Pharmacological Reports ( Pharmacological Reports ) 72 ( 3 ) 622 - 630 2020年06月

BACKGROUND: The purpose of this study was to evaluate the effects of concentrations of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein (LDL) cholesterol by the mammalian target of rapamycin (mTOR) inhibitor everolimus and their effects on genetic polymorphisms in the PCSK9 and mTORC1 genes in 53 renal transplant recipients. METHODS: Prior to and on day 15 after everolimus administration, the concentrations of everolimus in blood and PCSK9 and LDL cholesterol in plasma were evaluated. Additionally, mTORC1 (rs2536T>C and rs2295080T>G) and PCSK9 (rs505151G>A, rs562556G>A, and rs11593680C>T) polymorphisms were analyzed. RESULTS: Mean PCSK9 plasma concentrations on day 15 after everolimus treatment were significantly higher than those before treatment (295 versus 214 ng/mL, respectively; p = 0.004). Significant correlations between the area under the blood concentration-time curves (AUC)0-12 on day 15 of everolimus treatment and the change rate in PCSK9 concentrations were found (r = 0.316, p = 0.021). However, there were no significant correlations between the change rate in PCSK9 and LDL cholesterol concentrations. The change rate in PCSK9 concentrations by everolimus treatment was significantly greater in patients with the mTORC1 rs2295080G allele than the T/T genotype (p = 0.006); however, there were no significant differences between PCSK9 rs505151G>A and rs11583680C>T genotypes. In multivariate analyses, patients with mTORC1 rs2295080G (p = 0.010), higher everolimus AUC0-12 (p = 0.006), and female sex (p = 0.029) showed higher change rates of PCSK9 following everolimus therapy. CONCLUSIONS: Administration of everolimus significantly elevated plasma PCSK9 concentrations, potentially causing everolimus-induced hyperlipidemia.

DOI PubMed

Salvage Radiotherapy Versus Hormone Therapy for Prostate-specific Antigen Failure After Radical Prostatectomy: A Randomised, Multicentre, Open-label, Phase 3 Trial (JCOG0401)<sup>†</sup>[Formula presented]

Yokomizo A.

European Urology ( European Urology ) 77 ( 6 ) 689 - 698 2020年06月

BACKGROUND: No standard therapy has been established for localised prostate cancer patients with prostate-specific antigen (PSA) failure after radical prostatectomy (RP). OBJECTIVE: To determine whether radiotherapy ± hormone therapy is superior to hormone therapy alone in such patients. DESIGN, SETTING, AND PARTICIPANTS: This study is a multicentre, randomised, open-label, phase 3 trial. Patients with localised prostate cancer whose PSA concentrations had decreased to <0.1 ng/ml after RP, and then increased to 0.4-1.0 ng/ml, were randomised to the salvage hormone therapy (SHT) group (80 mg bicalutamide [BCL] followed by luteinising hormone-releasing hormone agonist in case of BCL failure) or the salvage radiation therapy (SRT) ± SHT group (64.8 Gy of SRT followed by the same regimen as in the SHT group in case of SRT failure). From May 2004 to May 2011, 210 patients (105 in each arm) were registered, with the median follow-up being 5.5 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to treatment failure (TTF) of BCL. RESULTS AND LIMITATIONS: TTF of BCL was significantly longer in the SRT ± SHT group (8.6 yr) than in the SHT group (5.6 yr; hazard ratio 0.56, 90% confidence interval [0.40-0.77]; one-sided p = 0.001). Thirty-two of 102 patients (31%) in the SRT ± SHT group did not have SRT treatment failure. However, clinical relapse-free survival and overall survival did not differ between the arms. The most frequent grade 3-4 adverse event was erectile dysfunction (83 patients [80%] in the SHT group vs. 76 [74%] in the SRT ± SHT group). Limitations include the short follow-up periods and surrogate endpoint setting to allow definitive conclusions. CONCLUSIONS: Initial SRT prolongs TTF of BCL in patients with post-RP PSA failure, indicating that SRT ± SHT is more beneficial than SHT alone. PATIENT SUMMARY: Patients who have prostate-specific antigen failure after radical prostatectomy benefit from salvage radiation therapy prior to salvage hormone therapy.

DOI PubMed

ロボット支援腹腔鏡下腎部分切除術のアウトカムを検証する RAPN手術中に苦労した症例、非典型例に対するRAPNの検討

齋藤満, 成田伸太郎, 井上高光, 羽渕友則

泌尿器外科 ( 医学図書出版(株) ) 33 ( 臨増 ) 754 - 756 2020年06月

ロボット支援膀胱全摘除術 RARCの腫瘍学的諸問題

成田伸太郎, 齋藤満, 井上高光, 羽渕友則

泌尿器外科 ( 医学図書出版(株) ) 33 ( 臨増 ) 760 - 763 2020年06月

当科における後腹膜線維症のステロイドによる治療成績

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

泌尿器外科 ( 医学図書出版(株) ) 33 ( 臨増 ) 886 - 886 2020年06月

当院におけるロボット支援腹腔鏡下膀胱全摘の治療成績

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