小坂 威雄 (コサカ タケオ)

Kosaka, Takeo

写真a

所属(所属キャンパス)

医学部 泌尿器科学教室 (信濃町)

職名

専任講師

経歴 【 表示 / 非表示

  • 2000年
    -
    2002年06月

    防衛医科大学校病院・自衛隊中央病院・初任実務研修医

  • 2002年06月
    -
    2004年07月

    陸上自衛隊 第12後方支援衛生隊 

  • 2002年06月
    -
    2004年07月

    防衛医科大学校 泌尿器科 通修医

  • 2002年06月
    -
    2004年07月

    村山医療センター 泌尿器科 通修医, 非常勤研究医

  • 2004年08月
    -
    2006年07月

    防衛医科大学校 泌尿器科 専門研修医

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学歴 【 表示 / 非表示

  • 2008年04月
    -
    2012年03月

    慶應義塾, 大学院医学研究科, 外科系泌尿器

    大学院, 修了

  • 1994年04月
    -
    2000年03月

    防衛省 防衛医科大学校, 医学部, 医学科

    大学, 卒業

学位 【 表示 / 非表示

  • 医学博士, 慶應義塾, 課程, 2012年

免許・資格 【 表示 / 非表示

  • 日本がん治療学会 暫定教育医

  • 医師免許, 2000年05月

  • 日本泌尿器科学会 専門医, 2005年

  • 日本泌尿器科学会 指導医, 2010年

  • 日本がん治療学会 認定医, 2011年04月

 

研究分野 【 表示 / 非表示

  • 泌尿器科学

研究キーワード 【 表示 / 非表示

  • リキッドバイオプシー

  • 前立腺癌

  • 去勢抵抗性前立腺癌

  • 幹細胞医学

  • 抗がん剤耐性機構

研究テーマ 【 表示 / 非表示

  • CRPC進展メカニズム, 

    2000年06月
    -
    継続中

 

論文 【 表示 / 非表示

  • MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer

    Yasumizu Y., Rajabi H., Jin C., Hata T., Pitroda S., Long M.D., Hagiwara M., Li W., Hu Q., Liu S., Yamashita N., Fushimi A., Kui L., Samur M., Yamamoto M., Zhang Y., Zhang N., Hong D., Maeda T., Kosaka T., Wong K.K., Oya M., Kufe D.

    Nature Communications (Nature Communications)  11 ( 1 )  2020年12月

     概要を見る

    © 2020, The Author(s). Neuroendocrine prostate cancer (NEPC) is an aggressive malignancy with no effective targeted therapies. The oncogenic MUC1-C protein is overexpressed in castration-resistant prostate cancer (CRPC) and NEPC, but its specific role is unknown. Here, we demonstrate that upregulation of MUC1-C in androgen-dependent PC cells suppresses androgen receptor (AR) axis signaling and induces the neural BRN2 transcription factor. MUC1-C activates a MYC→BRN2 pathway in association with induction of MYCN, EZH2 and NE differentiation markers (ASCL1, AURKA and SYP) linked to NEPC progression. Moreover, MUC1-C suppresses the p53 pathway, induces the Yamanaka pluripotency factors (OCT4, SOX2, KLF4 and MYC) and drives stemness. Targeting MUC1-C decreases PC self-renewal capacity and tumorigenicity, suggesting a potential therapeutic approach for CRPC and NEPC. In PC tissues, MUC1 expression associates with suppression of AR signaling and increases in BRN2 expression and NEPC score. These results highlight MUC1-C as a master effector of lineage plasticity driving progression to NEPC.

  • A Japanese patient with ductal carcinoma of the prostate carrying an adenomatosis polyposis coli gene mutation: a case report

    Umeda K., Kosaka T., Nakamura K., Takeda T., Mikami S., Nishihara H., Oya M.

    Diagnostic Pathology (Diagnostic Pathology)  15 ( 1 )  2020年08月

     概要を見る

    © 2020 The Author(s). Background: Ductal carcinoma of the prostate is a histological subtype with a higher mortality than acinar adenocarcinoma. The number of cases is small and there are no treatment guidelines. We believe that this is the first report of ductal carcinoma of the prostate with an adenomatosis polyposis coli (APC) gene mutation in Japan. Case presentation: An 85-year-old man presented with gross hematuria, and a papillary tumor in the prostatic urethra that was diagnosed as ductal carcinoma of the prostate following transurethral resection. Genetic analysis found an APC mutation with loss of heterozygosity. Immunostaining revealed focal nuclear translocation of β-catenin. APC mutations associated with loss of β-catenin degradation in the Wnt signaling pathway and result in over accumulation of β-catenin are thought to increase mortality. In this patient, β-catenin migrated into tumor cell nuclei. Conclusion: To the best of our knowledge, this is the first report of ductal carcinoma of the prostate with an APC mutation in Japan. The development of a therapeutic Wnt inhibitor is discussed.

  • Type of patients in whom biochemical recurrence after radical prostatectomy can be observed without salvage therapy

    Matsumoto K., Niwa N., Hagiwara M., Kosaka T., Tanaka N., Takeda T., Morita S., Mizuno R., Shinojima T., Hara S., Asanuma H., Oya M.

    World Journal of Urology (World Journal of Urology)  38 ( 7 ) 1749 - 1756 2020年07月

    ISSN  07244983

     概要を見る

    © 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: To examine the prognosis after BCR with and without salvage therapy, including radiation and/or androgen deprivation. Methods: The study population consisted of 431 patients, all of whom underwent radical prostatectomy and developed BCR (PSA > 0.2 ng/mL). According to the two risk factors [Gleason score ≥ 8 and PSA-doubling time (DT) < 6 months], we divided the patients into two groups. The high/intermediate-risk group consisted of patients with both or one risk factor. On the other hand, patients with neither factor were in the low-risk group. We set the starting point at the timing of BCR, and the endpoints were development to castration-resistant prostate cancer (CRPC) and cancer-specific death. Results: During the mean follow-up period of 8.3 years after BCR, CRPC was observed in 49 patients (11.4%), and 21 patients (4.9%) died due to prostate cancer. We first divided the 191 high/intermediate-risk patients according to the PSA level (PSA < 1.0 ng/mL, PSA 1.0–4.0, and PSA > 4.0 or no therapy) at the initiation of salvage therapy, including radiation and/or androgen deprivation. We found that delayed (PSA > 4.0 ng/mL) or no salvage therapy was significantly associated with CRPC and cancer-specific death. In the 240 low-risk patients, Kaplan–Meier curves demonstrated no significant difference in CRPC-free survival or cancer-specific survival within 10 years from the timing of BCR. Conclusions: Observation after BCR without salvage therapy or delayed administration may be an option for low-risk patients with a Gleason score ≤ 7 and PSA-DT ≥ 6 months when their life expectancy is within 10 years.

  • External validation of the "optimal PSA follow-up schedule after radical prostatectomy” in a new cohort

    Yanai Y., Matsumoto K., Kosaka T., Takeda T., Tanaka N., Morita S., Mizuno R., Shinojima T., Asanuma H., Oya M.

    International Journal of Clinical Oncology (International Journal of Clinical Oncology)  25 ( 7 ) 1393 - 1397 2020年07月

    ISSN  13419625

     概要を見る

    © 2020, Japan Society of Clinical Oncology. Background: Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an increase in asymptomatic prostate-specific antigen (PSA). We previously reported the “optimal PSA follow-up schedule after RP”. The aim of this study was to confirm the usefulness and safety of that follow-up schedule in another cohort. Methods: We retrospectively reviewed the clinicopathological data of 798 consecutive patients who underwent radical prostatectomy between 2009 and 2017. We examined all PSA values measured during follow-up. Furthermore, we estimated the PSA value when we observed the “optimal PSA follow-up schedule” at each timing in the virtual follow-up. BCR was defined as an elevation of PSA to greater than 0.2 ng/ml, and the ideal PSA range for detection of BCR was regarded to be 0.2–0.4 ng/ml. Results: During the mean follow-up period of 5.8 years, BCR occurred in 115 (14.9%) patients and the frequency of virtual follow-up was significantly lower than the actual frequency. However, overlooking of BCR (detecting BCR when PSA exceeded 0.4 ng/ml) was observed in 17 patients, which is higher than the actual frequency of overlooking (12 patients). Therefore, we modified the follow-up schedule, which could achieve the lower follow-up frequency and a limited number of overlooking of BCR (7 patients). Conclusion: This external validation study revealed that the "modified optimal PSA follow-up schedule after RP" can reduce the frequency of PSA measurement with a limited risk of overlooking BCR.

  • Appropriate timing for a biochemical evaluation after adrenalectomy for unilateral aldosterone-producing adenoma

    Takamatsu K., Takeda T., Hattori S., Tanaka N., Morita S., Matsumoto K., Kosaka T., Mizuno R., Shinojima T., Kikuchi E., Asanuma H., Kurihara I., Itoh H., Oya M.

    Clinical Endocrinology (Clinical Endocrinology)  92 ( 6 ) 503 - 508 2020年06月

    ISSN  03000664

     概要を見る

    © 2020 John Wiley & Sons Ltd Context: The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. Objective: To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. Design and patients: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). Results: PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0 pg/mL, P <.001). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (presurgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, P <.001). ARR significantly decreased at 1POM (presurgery; 146.9, 1 POM; 26.3, P <.001) although ARC did not increase at 1POM. Among the 34 patients who had hypokalaemia presurgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM. The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial and 10 (6%) absent. Twenty-three (14%) patients were reclassified into different biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. Conclusion: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

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総説・解説等 【 表示 / 非表示

研究発表 【 表示 / 非表示

  • PREDICTING PROSTATE SPECIFIC ANTIGEN RECURRENCE AFTER RADICAL PROSTATECTOMY BY CLINICOPATHOLOGICAL FACTORS: SUITABILITY OF MAGNETIC RESONANCE IMAGING

    小坂 威雄

    JOURNAL OF UROLOGY, 2013年04月, ポスター(一般)

  • UNDETECTABLE TUMOR THROUGH PREOPERATIVE MRI PREDICTS ORGAN CONFINED DISEASE AND LOWER TUMOR VOLUME IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER

    小坂 威雄

    JOURNAL OF UROLOGY, 2013年04月, 口頭(一般)

  • THE DISTINCT ASSOCIATION BETWEEN PRIMARY TUMOR LOCATION AND THE PATTERNS OF METASTATIC SPREAD FOLLOWING RADICAL NEPHROURETERECTOMY IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA

    小坂 威雄

    JOURNAL OF UROLOGY, 2013年04月, 口頭(一般)

  • Does Pelvic Lymph Node Dissection Improve the Biochemical Relapse-Free Survival in Low-Risk Prostate Cancer Patients Treated by Laparoscopic Radical Prostatectomy?

    小坂 威雄

    JOURNAL OF ENDOUROLOGY, 2012年09月, 口頭(一般)

  • ELEVATED EXPRESSION OF ARYL HYDROCARBON RECEPTOR IN RENAL CELL CARCINOMA IS ASSOCIATED WITH CIGARETTE SMOKE AND THE PROGNOSIS

    小坂 威雄

    JOURNAL OF UROLOGY, 2009年04月

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競争的資金等の研究課題 【 表示 / 非表示

  • 難治性前立腺癌のシングルセル解析によるゲノムエピゲノム進化と腫瘍内不均一性の解明

    2020年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小坂 威雄, 基盤研究(B), 補助金,  代表

  • 前立腺癌における不均一性と可塑性を標的とした新規バイオマーカー探索と新規治療戦略

    2017年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小坂 威雄, 基盤研究(C), 補助金,  代表

  • 旭化成ファーマ第11回研究助成:優秀腫瘍基礎研究テーマ

    2010年
    -
    2012年

    代表

  • 前立腺研究財団 研究助成 

    2009年
    -
    2010年

知的財産権等 【 表示 / 非表示

  • 抗がん剤の効果増強薬

    特願: 2012-127405   

    特許: 5947623 

    特許, 共同, 国内出願

受賞 【 表示 / 非表示

  • AUA Annual Meeting Best of Posters

    2018年

    受賞区分: 国内外の国際的学術賞

  • 16th Urological Association of Asia Congress; Best Abstract Award

    2018年

    受賞区分: 国内外の国際的学術賞

  • 第16回関東ホルモンと癌研究会 研究奨励賞

    2016年

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 第103回日本泌尿器科学会総会 総会賞

    2015年, 日本泌尿器科学会

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 慶應義塾大学医学部 三四会奨励賞

    2014年

    受賞区分: 塾内表彰等

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担当授業科目 【 表示 / 非表示

  • 泌尿器科学講義

    2021年度

  • 泌尿器科学講義

    2020年度

  • 泌尿器科学講義

    2019年度

教育活動及び特記事項 【 表示 / 非表示

  • 第5回 HBOC教育セミナー テキスト

    2018年10月

    , 教科書・教材の開発

  • 第4回 HBOC教育セミナー テキスト

    2018年05月

    , 教科書・教材の開発

  • 第3回 HBOC教育セミナー テキスト

    2018年02月

    , 教科書・教材の開発

  • 第2回 HBOC教育セミナー テキスト

    2017年06月

    , 教科書・教材の開発

  • 第1回 HBOC教育セミナー テキスト

    2017年02月

    , 教科書・教材の開発

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社会活動 【 表示 / 非表示

  • PSAスクリーニングキャンペーン

    2012年
    -
    継続中

委員歴 【 表示 / 非表示

  • 2015年04月
    -
    継続中

    プログラム委員, 前立腺研究財団