研究等業績 - その他 - 羽渕 友則
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Tanaka T.
International Journal of Urology ( International Journal of Urology ) 27 ( 12 ) 1095 - 1100 2020年12月
OBJECTIVES: To investigate the efficacy and safety of first-line nivolumab plus ipilimumab for patients treated with metastatic renal cell carcinoma. METHODS: We retrospectively evaluated 52 metastatic renal cell carcinoma patients who were treated with nivolumab plus ipilimumab between August 2015 and January 2020. Data on patient characteristics, treatment parameters and adverse events were obtained. Oncological outcomes were assessed according to the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model. Furthermore, differences in treatment parameters between patients with objective response (responders) and non-responders were compared. RESULTS: The median age and follow-up periods were 69 years and 8.2 months, respectively. The 1-year progression-free survival and overall survival rates were 55% and 75%, respectively. The objective response rate was 39%, and it was significantly different between the International Metastatic Renal Cell Carcinoma Database Consortium intermediate- and poor-risk groups (52% vs 24%). We observed 36 (69%) any immune-related adverse events, and 19 (37%) severe immune-related adverse events (grades III-V). The International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and higher value of initial C-reactive protein (≥1.0 mg/dL) were significantly associated with non-responders. Patients with two factors (the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group plus C-reactive protein ≥1.0 mg/dL) had a significantly poor overall survival than those with none or a single factor. CONCLUSIONS: In our experience, treatment response to nivolumab plus ipilimumab is comparable with that of the CheckMate 214 clinical trial, but the incidence of treatment-related adverse events is lower. The International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and initial C-reactive protein value might have a prognostic value for poor survival.
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Numakura K.
Scientific Reports ( Scientific Reports ) 10 ( 1 ) 20089 - 20089 2020年12月
Axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor, will be used in combination first-line therapies against metastatic renal cell carcinoma (mRCC), but its effects as a first-line monotherapy are unclear. Thus, we aimed to elucidate pretreatment clinical factors that predict the prognosis of patients with mRCC receiving first-line axitinib therapy. We enrolled 63 patients with mRCC treated with axitinib as first-line therapy between Nov. 2003 and Jul. 2018. Progression-free survival (PFS) and overall survival (OS) were assessed using the Wald χ2 statistic in Cox proportional hazards regression. Median patient age was 67 (range: 25-85) years. Seven (11.1%) patients were classified as being at favorable risk, 33 (52.4%) at intermediate risk, and 23 (36.5%) at poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification system. Median follow-up duration after axitinib initiation was 14 (range: 1-72) months. Median PFS and OS were 18 months and 65 months, respectively. Cox regression analyses of clinical predictors revealed that high C-reactive protein (CRP) levels were significantly correlated with shorter PFS [hazard ratio (HR), 1.63; 95% confidence interval (CI) 1.7-4.0)], whereas spindle cells and poor IMDC risk scores were related to worse OS (HR, 2.87 and 2.88, respectively; 95% CI 1.4-11.0 and 1.1-8.5, respectively). Thus, patients with mRCC and spindle histology or poor IMDC risk scores had worse OS, and those with high CRP levels had shorter PFS in first-line axitinib treatment. Other therapies might be more suitable for initial management of such patients.
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Post-mortem Plasma Cell-Free DNA Sequencing: Proof-of-Concept Study for the “Liquid Autopsy”
Takai E.
Scientific Reports ( Scientific Reports ) 10 ( 1 ) 2120 - 2120 2020年12月
Recent genomic studies on cancer tissues obtained during rapid autopsy have provided insights into the clonal evolution and heterogeneity of cancer. However, post-mortem blood has not been subjected to genetic analyses in relation to cancer. We first confirmed that substantial quantities of cell-free DNA were present in the post-mortem plasma of 12 autopsy cases. Then, we focused on a pilot case of prostate cancer with multiple metastases for genetic analyses. Whole-exome sequencing of post-mortem plasma-derived cell-free DNA and eight frozen metastatic cancer tissues collected during rapid autopsy was performed, and compared their mutational statuses. The post-mortem plasma cell-free DNA was successfully sequenced and 344 mutations were identified. Of these, 160 were detected in at least one of the metastases. Further, 99% of the mutations shared by all metastases were present in the plasma. Sanger sequencing of 30 additional formalin-fixed metastases enabled us to map the clones harboring mutations initially detected only in the plasma. In conclusion, post-mortem blood, which is usually disposed of during conventional autopsies, can provide valuable data if sequenced in detail, especially regarding cancer heterogeneity. Furthermore, post-mortem plasma cell-free DNA sequencing (liquid autopsy) can be a novel platform for cancer research and a tool for genomic pathology.
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Honma N.
Health Science Reports ( Health Science Reports ) 3 ( 4 ) e197 2020年12月
BACKGROUND AND AIMS: Vascular endothelial growth factor-directed therapies play a significant role in patients with metastatic renal cell carcinoma (mRCC). Biomarkers for predicting treatment efficacy and resistance are required to develop personalized medicine. We evaluated multiple serum cytokine levels in patients with mRCC treated with axitinib to explore predictive biomarkers. METHODS: From September 2012 to October 2015, serum samples were collected from 44 patients with mRCC before treatment and 4 weeks after axitinib initiation. Bio-Plex Pro Human Cancer Biomarker Panels 1 and 2 were used to measure levels of 34 serum biomarkers related to angiogenesis and cell proliferation. RESULTS: Patients with partial response or stable disease had significantly decreased serum plasminogen activator inhibitor-1 (PAI-1) level from pre-treatment to 4 weeks after axitinib initiation compared with those with progressive disease (P = .022). The median progression-free survival (PFS) and median overall survival (OS) in patients with increased serum PAI-1 level from pre-treatment to 4 weeks after axitinib initiation were significantly shorter than those with decreased serum PAI-1 level (P = .027 and P = .026, respectively). Increased serum PAI-1 level from pre-treatment to 4 weeks after axitinib initiation was an independent prognostic marker for shorter PFS and OS in multivariate analyses (P = .015 and P = .032, respectively). The immunohistochemical staining intensity of PAI-1 in tumor specimens was significantly associated with Fuhrman grade and presence of distant metastasis (P = .026 and P = .010, respectively). CONCLUSIONS: The initial change in serum PAI-1 level in the early stage of axitinib treatment could be a useful prognostic biomarker in patients with mRCC.
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Yamamoto R.
Transplant Immunology ( Transplant Immunology ) 63 101330 - 101330 2020年12月
Innate immune reactions are believed to be associated with ischemia/reperfusion injury (IRI), and IRI might be treatable by expanding regulatory T cells (Tregs), which can suppress the excessive responses of the immune system. Organ IRI is known to be closely involved in the expression of costimulatory molecules. The present study aimed to assess whether Tregs endogenously expanded by the administration of trichostatin A (TsA), a histone deacetylase inhibitor, could reduce renal IRI and to clarify their association with the expression of costimulatory molecules in a murine model. In this study, the wild-type mice used for an IRI model were randomly divided into the following four treatment groups: TsA group, DMSO group (control), DMSO+PC61 group, and TsA + PC61 group. Renal injury in the early phase after IRI was ameliorated in the TsA group (increased Tregs) when compared with the other groups. After renal IRI, both the mRNA and the protein levels of anti-inflammatory cytokines, IL-10 and TGF-β in the kidney and spleen were significantly higher in the TsA group than in the other groups, whereas the IL-6 levels were significantly lower in the TsA group than in the other groups. These results were offset by the administration of PC61, supporting that the renoprotective effect of TsA in this study is Treg dependent. mRNA expression levels of CD80, CD86, and ICAM-1 were lower in the TsA group, consistent with Treg control of injury through costimulatory molecules. Our findings suggest that endogenously expanded Tregs coordinate postischemic immune responses and decrease the expression of costimulatory molecules after renal IRI, and thus, they might ameliorate renal IRI. TsA administration for expanding Tregs is a promising therapeutic strategy for renal IRI.
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BCG膀胱内注入療法におけるレボフロキサシンの効果に関する検討 非盲検多施設共同無作為比較試験
沼倉 一幸, 小林 瑞貴, 石田 俊哉, 岡根 克己, 鈴木 一正, 下田 直威, 鈴木 丈博, 熊澤 光明, 佐々木 隆聖, 福田 歴視, 成田 伸太郎, 井上 高光, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1831 - 1831 2020年12月
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HSD3B1およびSRD5A2におけるミスセンス遺伝子多型によるアビラテロン治療効果予測
塩田 真己, 赤松 秀輔, 成田 伸太郎, 住吉 崇幸, 藤原 真希, 小川 修, 羽渕 友則, 江藤 正俊
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 850 - 850 2020年12月
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ホスホイノシタイド(PIPs)アシル基飽和度が前立腺癌進展に与える影響
小泉 淳, 成田 伸太郎, 中西 広樹, 奈良 健平, 神田 壮平, 沼倉 一幸, 黄 明国, 齋藤 満, 井上 高光, 佐藤 滋, 吉岡 年明, 羽渕 友則, 佐々木 雄彦
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 476 - 476 2020年12月
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ホルモン感受性転移性前立腺癌における診断時PSA低値は予後不良因子である
小玉 寛健, 畠山 真吾, 星 宣次, 川口 俊明, 石戸谷 滋人, 下田 次郎, 三塚 浩二, 土谷 順彦, 荒井 陽一, 羽渕 友則, 大山 力
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1449 - 1449 2020年12月
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ロボット支援手術時代における泌尿器腹腔鏡技術認定制度の意義と今後のあり方
羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 259 - 259 2020年12月
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ロボット支援膀胱全摘除術における尿路変向の標準化を目指して
成田 伸太郎, 齋藤 満, 井上 高光, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 328 - 328 2020年12月
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上部尿路上皮癌に対する腎尿管全摘術におけるリンパ節郭清が予後に与える影響
小林 瑞貴, 井上 高光, 奈良 健平, 神田 壮平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 佐藤 滋, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1263 - 1263 2020年12月
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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, 星 宣次, 三塚 浩二, 川村 貞文, 土谷 順彦, 大山 力, 荒井 陽一, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1556 - 1556 2020年12月
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初診時有転移内分泌感受性前立腺癌のBMIとアウトカムの関連
石田 雅宣, 成田 伸太郎, 野村 恭子, 畠山 真吾, 高橋 正博, 川村 貞文, 星 宣次, 三塚 浩二, 土谷 順彦, 大山 力, 荒井 陽一, 羽渕 友則, みちのく泌尿器癌研究班
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1459 - 1459 2020年12月
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当科における化学療法抵抗性尿路上皮癌に対するPembrolizumabの初期使用経験
菊池 茜恵, 神田 壮平, 井上 高光, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 佐藤 滋, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1849 - 1849 2020年12月
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当科における高齢者の精巣腫瘍に対する導入化学療法の成績
奈良 健平, 成田 伸太郎, 小泉 淳, 山本 竜平, 神田 壮平, 沼倉 一幸, 齋藤 満, 井上 高光, 佐藤 滋, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1717 - 1717 2020年12月
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抗血液型抗体価と急性抗体関連型拒絶反応発症の関連性
山本 竜平, 齋藤 満, 提箸 隆一郎, 齋藤 拓郎, 小泉 淳, 奈良 健平, 神田 壮平, 沼倉 一幸, 成田 伸太郎, 井上 高光, 佐藤 滋, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1653 - 1653 2020年12月
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新規アンドロゲン受容体シグナル阻害薬は転移性去勢抵抗性前立腺癌の予後を改善したか? 多施設共同後ろ向き研究
岩村 大径, 畠山 真吾, 成田 伸太郎, 櫻井 俊彦, 川村 貞文, 星 宣次, 三塚 浩二, 荒井 陽一, 伊藤 明宏, 土谷 順彦, 羽渕 友則, 大山 力
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 1324 - 1324 2020年12月
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日本人の転移性ホルモン感受性前立腺癌におけるGleason Pattern 5の意義についての解析
諸角 謙人, 三塚 浩二, 成田 伸太郎, 川村 貞文, 栃木 達夫, 櫻井 俊彦, 土屋 順彦, 畠山 真吾, 大山 力, 羽渕 友則, 荒井 陽一, 高橋 正博, 伊藤 明宏, みちのく泌尿器癌研究グループ
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 848 - 848 2020年12月
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移植腎における三次リンパ組織の臨床的意義
齋藤 満, 李 有鎬, 佐藤 有紀, 成田 伸太郎, 井上 高光, 佐藤 滋, 柳田 素子, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 108回 873 - 873 2020年12月