研究者詳細 - 大家　基嗣

論文 - 大家　基嗣

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The Intracellular Metabolic Reprogramming enables Urothelial Carcinoma Cells to Acquire Chemoresistance

Shigeta Keisuke, Hasegawa Masanori, Kikuchi Eiji, Kosaka Takeo, Mizuno Ryuichi, Oya Mototsugu

CANCER SCIENCE （(一社)日本癌学会） 112 246 - 246 2021年02月

共著, ISSN 1347-9032

21水酸化酵素欠損症に巨大な両側副腎骨髄脂肪腫を合併した一例

松林秀幸, 武田利和, 馬場優人, 桝田司, 安水洋太, 田中伸之, 松本一宏, 森田伸也, 小坂威雄, 水野隆一, 浅沼宏, 大家基嗣

泌尿器外科（医学図書出版(株)） 34 （ 2 ） 210 - 210 2021年02月

共著, ISSN 0914-6180

Long-term follow-up comparing salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy.

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

International journal of clinical oncology （LIPPINCOTT WILLIAMS & WILKINS） 203 （ 4 ） E566 - E566 2021年01月

研究論文（学術雑誌）, 共著, ISSN 1341-9625

© 2021, Japan Society of Clinical Oncology. Background: The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). Methods: We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2 ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0 ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC). Results: During the mean follow-up period of 8.5 years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan–Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group ≥ 4 and PSA-doubling time < 6 months (10-year CRPC-free survival 73.4 vs. 40.3%, p = 0.040). Conclusion: This study revealed that salvage RT increases the CRPC-free survival rate compared with salvage ADT in high-risk patients with Grade Group ≥ 4 and PSA-doubling time < 6 months.

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Pulmonary metastasis secondary to abiraterone-resistant prostate cancer with homozygous deletions of BRCA2: First Japanese case.

Izawa M, Kosaka T, Nakamura K, Oba J, Hishida T, Hongo H, Mikami S, Nishihara H, Oya M

IJU case reports （IJU Case Reports） 4 （ 1 ） 14 - 17 2021年01月

共著

Introduction: Most metastatic prostate cancers acquire the capacity for androgen-independent growth and become resistant to androgen deprivation therapy. A patient-focused treatment strategy is needed for aggressive castration-resistant prostate cancer. Case presentation: We report the case of a 62-year-old man who presented with prostatic adenocarcinoma who was treated by radiation and combined androgen blockade. After completion of first-line therapy, he was diagnosed with multiple metastatic castration-resistant prostate cancer in the lung. Second-line therapy with abiraterone acetate resulted in partial remission of the lung metastases. Thoracic surgery was performed to remove the single lung metastasis remaining. Next-generation sequencing of the specimens demonstrated homozygous loss of BRCA2. We note in this case a heterogeneous response to abiraterone acetate may be related to the somatic BRCA2 deletions. Conclusions: We present the first Japanese case of a metastatic abiraterone acetate-resistant castration-resistant prostate cancer accompanied by BRCA2 mutation.

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AYA世代で外科的治療を要した先天性腎尿路異常と胎児超音波検査との関連

寺西悠, 浅沼宏, 安水洋太, 田中伸之, 武田利和, 松本一宏, 森田伸也, 小坂威雄, 水野隆一, 大家基嗣

日本腎泌尿器疾患予防医学研究会プログラム・抄録集（日本腎泌尿器疾患予防医学研究会） 29回 52 - 52 2021年01月

共著

Transient hypercalcemia in a patient with SAPHO syndrome

Yoshida T., Oya M.

Journal of General and Family Medicine （Journal of General and Family Medicine） 23 （ 1 ） 44 - 46 2021年

ISSN 2189-7948

We here report a case of SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome with hypercalcemia. The patient was diagnosed with SAPHO syndrome at the age of 54, because he exhibited osteitis and hyperostosis around the sternoclavicular joints and the temporomandibular joints bilaterally and had past medical history of palmoplantar pustulosis. At the age of 67, he exhibited appetite loss and nausea. Corrected serum calcium was 13.0 mg/dl. Adequate hydration was recommended, and his calcium levels returned to the normal range without any medical treatment. Although speculative, his hypercalcemia was considered to be caused by an increased bone activity in SAPHO syndrome. This is the first report describing transient hypercalcemia in a patient with SAPHO syndrome.

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Successful Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis-Associated Rapidly Progressive-Interstitial Lung Disease by Plasma Exchange: Two Case Reports.

Takahashi R, Yoshida T, Morimoto K, Kondo Y, Kikuchi J, Saito S, Ishigaki S, Kaneko Y, Takeuchi T, Itoh H, Oya M

Clinical medicine insights. Case reports （Clinical Medicine Insights: Case Reports） 14 11795476211036322 - 11795476211036322 2021年

共著, ISSN 1179-5476

Background: Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) are frequently accompanied by rapidly progressive-interstitial lung disease (RP-ILD). They are often refractory to intensive immunosuppressive therapy and have poor prognosis. Case presentation: A 73-year-old woman presented with fever, cold symptoms, and skin eruption for a month. She also exhibited muscle weakness on upper extremities slightly. The titer of anti-MDA5 antibody was extremely high, and computed tomography showed ground glass opacity and reticular shadows in the lungs. She was diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD and treated with intensive immunosuppressive therapy. However, the titer of anti-MDA5 antibody did not decrease satisfactorily, and plasma exchange was alternatively initiated. The titer decreased remarkably, and she obtained disease remission. Similarly, a 63-year-old woman presented with stiffness of the neck and hands, fever and cough. She was also diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD, because she had skin eruptions, slight muscle weakness, an elevation in anti-MDA5 antibody, and RP-ILD. She was unresponsive to intensive immunosuppressive therapy, but plasma exchange successfully improved the titer of anti-MDA5 antibody, the symptoms, and the findings of computed tomography. Conclusions: Although anti-MDA5 antibody-positive DM-associated RP-ILD has a high mortality rate, this report suggests the usefulness of plasma exchange to improve the prognosis.

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A Case of New-Onset Systemic Lupus Erythematosus With Serositis in a Maintenance Hemodialysis Patient.

Kosugi S, Yoshida T, Yoshimoto N, Itoh H, Oya M

Clinical medicine insights. Case reports （Clinical Medicine Insights: Case Reports） 14 11795476211056172 2021年

ISSN 1179-5476

A 61-year-old woman with a 4-year history of maintenance hemodialysis due to end-stage renal disease of unknown cause was admitted because of a recurrent fever and abdominal pain lasting for 3 months. She had rheumatoid arthritis as a complication and had taken sulfasalazine for over 4 years. Laboratory data revealed thrombocytopenia, hypocomplementemia, a high C-reactive protein level, and positivity for antinuclear antibody and anti-double strand DNA antibody. Gallium scintigraphy showed pericarditis, pleuritis, and peritonitis. Nonscarring alopecia was also noted. She was diagnosed as having systemic lupus erythematosus (SLE). Drug-induced lupus elicited by sulfasalazine was ruled out because the symptoms did not improve even after the discontinuation of the drug upon admission. Oral prednisolone treatment markedly improved her symptoms and laboratory data. However, she later died of sepsis arising from proctitis on day 71 of admission. This report underscores the necessity of considering new-onset SLE in patients with unexplained fever and serositis, including pleuritis, peritonitis, or pericarditis, even if they are receiving maintenance dialysis.

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Role of prior nephrectomy for synchronous metastatic renal cell carcinoma (mRCC) on efficacy in patients treated with avelumab plus axitinib (A plus Ax) or sunitinib (S): Results from JAVELIN Renal 101

Grimm M-O., Oya M., Choueiri T. K., Schmidinger M., Quinn D. I., Mescam G. Gravis, Verzoni E., Van den Eertwegh A. J. M., di Pietro A., Mariani M., Wang J., Thomaidou D., Albiges L.

ANNALS OF ONCOLOGY 32 S690 - S691 2021年

ISSN 0923-7534

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Genomic profiling of circulating tumor DNA in advanced genitourinary cancer patients: SCRUM-Japan MONSTAR SCREEN Nationwide Cancer Genome Screening Project

Kato T., Matsubara N., Fujisawa T., Shiota M., Eto M., Osawa T., Abe T., Shinohara N., Yasumizu Y., Tanaka N., Oya M., Nishimoto K., Horasawa S., Kuramoto N., Nakamura Y., Taniguchi H., Yoshino T., Nonomura N.

ANNALS OF ONCOLOGY 32 S656 - S656 2021年

ISSN 0923-7534

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MUC1-C ACTIVATES THE BAF (mSWI/SNF) COMPLEX IN PROSTATE CANCER STEM CELLS.

Hagiwara M, Yasumizu Y, Yamashita N, Rajabi H, Fushimi A, Long MD, Li W, Bhattacharya A, Ahmad R, Oya M, Liu S, Kufe D

Cancer research （AMER ASSOC CANCER RESEARCH） 81 （ 4 ） 1111 - 1122 2020年12月

研究論文（学術雑誌）, 共著, ISSN 0008-5472

© 2020 American Association for Cancer Research. The Brg/Brahma-associated factor (BAF, mSWI/SNF) chromatin remodeling complex is of importance in development and has been linked to prostate oncogenesis. The oncogenic MUC1-C protein promotes lineage plasticity in the progression of neuroendocrine prostate cancer (NEPC), however, there is no known association between MUC1-C and BAF. We report here that MUC1-C binds directly to the E2F1 transcription factor and that the MUC1-C!E2F1 pathway induces expression of embryonic stem cell–specific BAF (esBAF) components BRG1, ARID1A, BAF60a, BAF155, and BAF170 in castrate-resistant prostate cancer (CRPC) and NEPC cells. In concert with this previously unrecognized pathway, MUC1 was associated with increased expression of E2F1 and esBAF components in NEPC tumors as compared with CRPC, supporting involvement of MUC1-C in activating the E2F1!esBAF pathway with progression to NEPC. MUC1-C formed a nuclear complex with BAF and activated cancer stem cell (CSC) gene signatures and the core pluripotency factor gene network. The MUC1-C!E2F1!BAF pathway was necessary for induction of both the NOTCH1 effector of CSC function and the NANOG pluripotency factor, and collectively, this network drove CSC self-renewal. These findings indicate that MUC1-C promotes NEPC progression by integrating activation of E2F1 and esBAF with induction of NOTCH1, NANOG, and stemness. Significance: These findings show that MUC1-C, which promotes prostate cancer progression, activates a novel pathway that drives the BAF remodeling complex, induces NOTCH1 and NANOG, and promotes self-renewal of prostate cancer stem cells.

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副腎性クッシング症候群における術後ステロイド補充療法の長期化を予測する因子の検討

箱崎恭平, 武田利和, 山田祥岳, 安水洋太, 田中伸之, 松本一宏, 森田伸也, 小坂威雄, 水野隆一, 浅沼宏, 陣崎雅弘, 大家基嗣

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 1140 - 1140 2020年12月

共著

脱細胞化臓器骨格を用いた腎臓再生

八木洋, 黒田康平, 田島一樹, 蛭川和也, 水野隆一, 大家基嗣, 北川雄光

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 878 - 878 2020年12月

共著

Treatment-free survival after discontinuation of immno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: retrospective study of Japanese metastatic renal cell carcinoma patients(AFTER I-O study)(和訳中)

山名一寿, 大家基嗣, 木村剛, 深沢賢, 沼倉一幸, 杉山豊, 内藤整, 加峰弘毅, 田嶋洋平, 冨田善彦

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（ 6 ） 675 - 675 2020年12月

ISSN 0732-183X

Efficacy and safety of darolutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a sub-group analysis of the phase III ARAMIS trial.

Uemura H, Matsushima H, Kobayashi K, Mizusawa H, Nishimatsu H, Fizazi K, Smith M, Shore N, Tammela T, Tabata KI, Matsubara N, Iinuma M, Uemura H, Oya M, Momma T, Kawakita M, Fukasawa S, Kobayashi T, Kuss I, Le Berre MA, Snapir A, Sarapohja T, Suzuki K

International journal of clinical oncology （SPRINGER JAPAN KK） 26 （ 3 ） 578 - 590 2020年11月

研究論文（学術雑誌）, 共著, ISSN 1341-9625

BACKGROUND: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. RESULTS: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11-0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. CONCLUSIONS: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.

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特集泌尿器科医のためのクリニカル・パール-いま伝えたい箴言・格言・アフォリズム〈下部尿路機能障害/小児・女性・アンドロロジー/結石・感染症/腎不全編〉企画にあたって

大家基嗣

臨床泌尿器科（株式会社医学書院） 74 （ 12 ） 903 - 903 2020年11月

ISSN 0385-2393

Proton pump inhibitors may hinder hypophosphatemic effect of lanthanum carbonate, but not of ferric citrate hydrate or sucroferric oxyhydroxide, in hemodialysis patients.

Minakuchi H, Yoshida T, Kaburagi N, Fujino T, Endo S, Takemitsu TY, Yamashita N, Itoh H, Oya M

Renal failure （Renal Failure） 42 （ 1 ） 799 - 806 2020年11月

研究論文（学術雑誌）, 共著, ISSN 0886-022X

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Because end-stage renal disease patients undergoing hemodialysis frequently take acid suppressants for the treatment or prevention of gastrointestinal diseases, it is important to clarify the drug-interactions between acid suppressants and phosphate binders on the control of serum phosphate levels. In the present study, we examined whether the phosphate-lowering effects of three phosphate binders, lanthanum carbonate (LC), ferric citrate hydrate (FCH), and sucroferric oxyhydroxide (SFOH), were affected by proton pump inhibitors (PPIs) in maintenance hemodialysis patients. Laboratory data for 71 patients who had been newly prescribed one of the three phosphate binders were examined. LC at a dosage of 500 ± 217 mg/day significantly decreased serum phosphate levels by −18% in the absence of a PPI (n = 9), while a dosage of 700 ± 230 mg/day only decreased it by −3% in the presence of a PPI (n = 10). Thus, the efficacy of LC in reducing serum phosphate levels was significantly hindered by the presence of PPIs. FCH significantly decreased serum phosphate levels by −18% in the absence of a PPI (n = 7, FCH: 571 ± 189 mg/day) and by −17% in the presence of a PPI (n = 20, FCH: 638 ± 151 mg/day). The decrease in serum phosphate levels by SFOH (393 ± 197 mg/day) was −7% in the absence of a PPI (n = 7), and SFOH at a dosage of 556 ± 316 mg/day significantly decreased serum phosphate levels by −13% in the presence of a PPI (n = 18). These results suggest that the phosphate-lowering effect of LC, but not of FCH or SFOH, is diminished in the presence of PPIs in hemodialysis patients.

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Difficulty in differential diagnosis for renal cancer with microscopic papillary architecture: overlapped pathological features among papillary renal cell carcinoma (RCC), mutinous tubular and spindle cell carcinoma, and unclassified RCC. Lessons from a Japanese multicenter study.

Ito K, Mikami S, Kuroda N, Nagashima Y, Tatsugami K, Masumori N, Kondo T, Takagi T, Nakanishi S, Eto M, Kamba T, Tomita Y, Matsuyama H, Tsushima T, Nakazawa H, Oya M, Kimura G, Shinohara N, Asano T

Japanese journal of clinical oncology （Japanese journal of clinical oncology） 50 （ 11 ） 1313 - 1320 2020年10月

研究論文（学術雑誌）, 共著, ISSN 0368-2811

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. OBJECTIVES: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. METHODS: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. RESULTS: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years. CONCLUSION: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.

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特集泌尿器科医のためのクリニカル・パール-いま伝えたい箴言・格言・アフォリズム〈腫瘍/処置・救急・当直編〉企画にあたって

大家基嗣

臨床泌尿器科（株式会社医学書院） 74 （ 11 ） 815 - 815 2020年10月

ISSN 0385-2393

CDK12 and HER2 co-amplification in two urothelial carcinomas with rapid and aggressive clinical progression.

Yanai Y, Kosaka T, Nakamura K, Aimono E, Matsumoto K, Morita S, Mikami S, Nishihara H, Oya M

Cancer science （Cancer Science） 111 （ 12 ） 4652 - 4655 2020年10月

研究論文（学術雑誌）, 共著, ISSN 1347-9032

© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Cyclin-dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb-B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next-generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor-2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.

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