Faculty Profiles - NASU Yasutomo

Papers - NASU Yasutomo

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The Novel Combination of Nitroxoline and PD-1 Blockade, Exerts a Potent Antitumor Effect in a Mouse Model of Prostate Cancer. Reviewed International journal

Naijin Xu, Linglong Huang, Xiezhao Li, Masami Watanabe, Chaoming Li, Abai Xu, Chunxiao Liu, Qiang Li, Motoo Araki, Koichiro Wada, Yasutomo Nasu, Peng Huang

International journal of biological sciences 15 ( 5 ) 919 - 928 2019

Language：English Publishing type：Research paper (scientific journal)

Programmed cell death protein 1 (PD-1) blockade is a promising therapeutic strategy against prostate cancer. Nitroxoline has been found to have effective anticancer properties in several cancer types. We investigated the efficacy of a combination therapy involving nitroxoline and PD-1 blockade in a prostate cancer mouse model. In our in vitro analysis, we found that nitroxoline inhibited the viability and proliferation of the mouse prostate cancer cell line RM9-Luc-PSA. Additionally, nitroxoline downregulated the expressions of phospho-PI3 kinase, phospho-Akt (Thr308), phospho-Akt (Ser473), phospho-GSK-3β, Bcl-2, and Bcl-xL. Nitroxoline also downregulated programmed death-ligand 1 (PD-L1) expression levels in prostate cancer cell line and tumor tissue. In our murine prostate cancer orthotopic model, nitroxoline plus PD-1 blockade synergistically suppressed tumor growth when compared with nitroxoline or PD-1 blockade alone, leading to reductions in tumor weight, bioluminescence tumor signals, and serum prostate-specific antigen levels. Furthermore, fluorescence-activated cell sorting analysis showed that the combination strategy significantly enhanced antitumor immunity by increasing CD44+CD62L+CD8+ memory T cell numbers and reducing myeloid-derived suppressor cell numbers in peripheral blood. In conclusion, our findings suggest that nitroxoline plus PD-1 blockade may be a promising treatment strategy in patients with prostate cancer.

DOI： 10.7150/ijbs.32259

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Favorable long-term oncological and urinary outcomes of incidental prostate cancer following holmium laser enucleation of the prostate. International journal

Yusuke Tominaga, Takuya Sadahira, Yosuke Mitsui, Yuki Maruyama, Ryuta Tanimoto, Koichiro Wada, Shuhei Munemasa, Nobuyuki Kusaka, Yasuhiro Nishiyama, Takushi Kurashige, Yasutomo Nasu, Shunji Hayata

Molecular and clinical oncology 10 ( 6 ) 605 - 609 2019

Language：English Publishing type：Research paper (scientific journal)

The aim of the present study was to investigate the impact of incidental prostate cancer (IPCa), which was diagnosed by holmium laser enucleation of the prostate (HoLEP), on long-term oncological and functional outcomes. A total of 482 patients who underwent HoLEP for benign prostatic hyperplasia (BPH) between 2008 and 2016 at our institution were retrospectively reviewed. We defined IPCa as prostate cancer (PCa) according to the enucleated tissue of transitional zone. Therefore, 64 patients were excluded for the following reasons: Prostate-specific antigen (PSA) ≥4.0 ng/ml and no prostate biopsy (n=46); and PSA ≥4.0 ng/ml and diagnosed with PCa by prostate biopsy performed during HoLEP (n=18). Notably, 418 patients were included in the study and divided into two groups: The BPH group and the IPCa group. For 5 years, postoperative PSA and functional outcomes were evaluated. Of 418 patients, 25 (6%) were diagnosed with IPCa by HoLEP, 21 patients (84%) had a Gleason score ≤6 and 5 patients (20%) received adjuvant therapy for PCa following HoLEP. No significant differences were observed between groups for preoperative PSA, PSA density, or urinary and sexual function outcomes; however, age at the time of HoLEP significantly differed between groups (71.7 vs. 75.5 years, P=0.026). Long-term (5-year) urinary outcomes demonstrated sustained improvement. Postoperative PSA increased gradually in the IPCa group (3-year, P=0.033; 4-year, P=0.037); International Index of Erectile Function 5 conversely decreased (5-year, P=0.068). According to the present results, if standard PSA screening and prostate biopsy are performed, watchful waiting for IPCa is feasible, and IPCa does not impact on 5-year urinary outcomes.

DOI： 10.3892/mco.2019.1839

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Burned-out Prostate Cancer ? Primary Metastatic Cancer Not Detected on Repeat Biopsy. Reviewed

Mitsui Y, Sadahira T, Maruyama Y, Wada K, Tanimoto R, Sugimoto M, Araki M, Watanabe M, Yanai H, Watanabe T, Nasu Y

Acta medica Okayama 72 ( 6 ) 605 - 609 2018.12

Language：English Publishing type：Research paper (scientific journal)

Metastatic prostate cancer (PCa) cases that cannot be detected on repeat prostate biopsy are extremely rare. Our patient was a 51-year-old Japanese man diagnosed as metastatic PCa by histopathological examination of lesions obtained bone biopsy and lymph node dissection. The primary tumor was not detected after repeated prostate biopsy. Metastatic PCa was diagnosed based on immunohistochemical staining: PSA, AR, P504S, and NKX3.1 of bone and lymph node with metastasis. We speculate that the primary PCa was "burned-out," demonstrating remote metastases with no apparent primary tumor in the prostate. Burned-out PCa may be difficult to diagnose and treat due to its rarity.

DOI： 10.18926/AMO/56380

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経腹的到達法による根治的腎摘除術

小林泰之, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 32回 SEP - 2 2018.11

ロボット支援下腎部分切除におけるearly unclamp法の術後腎機能に対する有用性の検討

和田里章悟, 谷本竜太, 丸山雄樹, 光井洋介, 前原貴典, 西村慎吾, 高本篤, 杉本盛人, 和田耕一郎, 小林泰之, 荒木元朗, 渡辺豊彦, 那須保友

西日本泌尿器科 80 ( 増刊 ) 189 - 189 2018.10

当院で経験した前立腺炎症性偽腫瘍の1例

佐久間貴文, 高本篤, 河村香澄, 岩田健宏, 和田耕一郎, 谷本竜太, 杉本盛人, 小林泰之, 荒木元朗, 渡邊豊彦, 柳井広之, 那須保友

西日本泌尿器科 80 ( 増刊 ) 176 - 176 2018.10

QOL向上をめざした泌尿器がん治療ロボット支援下膀胱全摘除術

小林泰之, 三井將雄, 佐古智子, 高本篤, 西村慎悟, 和田耕一郎, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 80 ( 増刊 ) 95 - 95 2018.10

THE PROMISING USE OF PROBIOTICS AGAINST RECURRENT URINARY TRACT INFECTIONS Reviewed

定平卓也, 和田耕一郎, 三井將雄, 石井亜矢乃, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 = The Nishinihon journal of urology 80 ( 10 ) 505 - 509 2018.10

Language：Japanese Publisher：西日本泌尿器科学会

尿路感染症に対する治療として中心的な役割を果たしてきた抗菌化学療法は大きな転機を迎えている。世界的な時流として耐性菌の問題や医療経済的にも抗菌薬の使用量を減少させる方向に移行している。尿路感染症においても例外ではなく、そのマネジメントに関して治療法の見直しだけでなく予防の重要性についての議論がなされている。そのうち、これまでに様々な臨床研究において有効性が確認されつつあるプロバイオティクスが抗菌薬とは異なる尿路感染症対策として注目されている。健常な閉経前の女性の腟内においては、基本的に乳酸菌が細菌叢(フローラ)を形成しているが、月経中や閉経後は乳酸菌が減少して腸内細菌が腟内に定着することとなる。その腟がリザーバーとなって細菌を供給し、頻繁に尿路の逆行性感染を引き起こすと考えられている。すなわち、腟内を乳酸菌中心のフローラに保つことで尿路感染症の再発(反復)リスクが低くなることが期待でき、実際にプロバイオティクスを用いた多くの研究が行われている。我々が現在行っている乳酸菌製剤のほか、プロバイオティクスの経口摂取が腟内フローラに与える影響に関しても検証が進んでおり、プロバイオティクスが尿路感染症の予防や治療に寄与することが期待されている。(著者抄録)

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鰓耳腎症候群の小児に対する生体腎移植の1例

窪田理沙, 荒木元朗, 和田耕一郎, 河村香澄, 丸山雄樹, 光井洋介, 西村慎吾, 小林泰之, 渡邉豊彦, 那須保友, 宮井貴之, 北川正史, 田邊克幸, 和田淳

移植 53 ( 総会臨時 ) 434 - 434 2018.9

生体腎移植におけるリツキシマブ投与の効果と有害事象

河村香澄, 荒木元朗, 丸山雄樹, 坪井一朗, 光井洋介, 窪田理沙, 西村真吾, 和田耕一郎, 小林泰之, 渡邉豊彦, 那須保友, 山下里美, 北川正史, 田邉克幸, 杉山斉, 和田淳

移植 53 ( 総会臨時 ) 481 - 481 2018.9

腎移植患者における24時間蓄尿から見る1日塩分・蛋白摂取量の意義

光井洋介, 荒木元朗, 丸山雄樹, 坪井一朗, 河村香澄, 窪田理沙, 西村慎吾, 和田耕一郎, 小林泰之, 渡辺豊彦, 北川正史, 田邊克之, 杉山斉, 和田淳, 那須保友

移植 53 ( 総会臨時 ) 475 - 475 2018.9

リツキシマブは腎移植レシピエントの周術期細菌感染症のリスクになるか

西村慎吾, 和田耕一郎, 荒木元朗, 山下里美, 坪井一朗, 河村香澄, 丸山雄樹, 光井洋介, 窪田理沙, 定平卓也, 谷本竜太, 小林泰之, 渡邉豊彦, 那須保友

移植 53 ( 総会臨時 ) 436 - 436 2018.9

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation Reviewed

Ryuta Tanimoto, Takashi Saika, Shin Ebara, Yasuyuki Kobayashi, Ryoji Nasu, Daisuke Yamada, Hitoshi Takamoto, Yoshiyuki Miyaji, Yasutomo Nasu, Tomoyasu Tsushima, Hiromi Kumon

World Journal of Urology 36 ( 6 ) 889 - 895 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Verlag

Purpose: Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. Methods: Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. Results: Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. Conclusions: Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

DOI： 10.1007/s00345-018-2196-8

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Renal Function after Nephrectomy Influences the Risk of Cardiovascular Events.

Taiki Kambara, Ryuta Tanimoto, Motoo Araki, Takashi Saika, Hideaki Hashimoto, Tadashi Oeda, Tomoyasu Tsushima, Shunji Hayata, Yasutomo Nasu, Yasuyuki Kobayashi

Acta medica Okayama 72 ( 3 ) 241 - 247 2018.6

Language：English Publishing type：Research paper (bulletin of university, research institution)

We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events.

DOI： 10.18926/AMO/56069

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Gene therapy for prostate cancer: Current status and future prospects

Yasutomo Nasu, Masami Watanabe

Hormone Therapy and Castration Resistance of Prostate Cancer 397 - 406 2018.5

Language：English Publishing type：Part of collection (book) Publisher：Springer Singapore

Prostate is an ideal target organ for gene therapy as a translational research. It has some advantages as follows: prostate is not a life keeping organ, can be approached easily by ultrasound as a routine clinical practice and PSA is a sensitive and useful tumor marker for the evaluation of clinical response. Intraprostatic therapeutic gene transduction (in situ gene therapy) is one of the potent therapeutic options for prostate cancer gene therapy aiming at antimetastatic benefits through the generation of immune cell-mediated cytotoxic activities that affect not only the primary tumor but also metastatic lesion. In this chapter, current outcome and future prospect of prostate cancer gene therapy are discussed.

DOI： 10.1007/978-981-10-7013-6_40

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Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with testicular cancer

Maruyama Y, Sadahira T, Mitsui Y, Takamoto A, Wada K, Tanimoto R, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y

The Journal of Urology 199 ( 4S ) e1131 - e1132 2018.5

Oncological impact of neoadjuvant hormonal therapy on permanent iodine-125 seed brachytherapy in patients with low- and intermediate-risk prostate cancer. International journal

Atsushi Takamoto, Ryuta Tanimoto, Kensuke Bekku, Motoo Araki, Takuya Sadahira, Koichiro Wada, Shin Ebara, Norihisa Katayama, Hiroyuki Yanai, Yasutomo Nasu

International journal of urology : official journal of the Japanese Urological Association 25 ( 5 ) 507 - 512 2018.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.

DOI： 10.1111/iju.13555

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Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with germ cell tumors. Reviewed International journal

Yuki Maruyama, Takuya Sadahira, Yosuke Mitsui, Motoo Araki, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Medical oncology (Northwood, London, England) 35 ( 6 ) 80 - 80 2018.4

Language：English Publishing type：Research paper (scientific journal)

Bleomycin pulmonary toxicity (BPT) has been well described in patients with germ cell tumors treated with bleomycin etoposide and cisplatin chemotherapy (BEP). To assess the prognostic impact of BPT, we retrospectively identified 52 patients who underwent bleomycin etoposide and cisplatin chemotherapy from 2008 to 2017 in our institution, and evaluated the risk factors of BPT and its effect on prognosis. Patients who had received chemotherapy at another institution were excluded. BPT was defined as bleomycin discontinuation in response to pulmonary function test decline, pulmonary symptoms, or interstitial pneumonia on computed tomography without infection. We divided the patients into two groups according to this definition: BPT and non-BPT. Their median age was 34.2 years, and their median body mass index was 22.8 kg/m2. Twenty patients had a smoking history, 37 were diagnosed with non-seminoma, and 20 had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified into the BPT group and 37 into the non-BPT group. Only body mass index < 22 was identified as a predictor of BPT in multivariable logistic models. Age or use of granulocyte-colony stimulating factor did not have a significant impact. Kaplan-Meier analysis revealed that the presence of BPT had no significant impact on either 5-year overall survival or progression-free survival. Lower body mass index can increase the risk of BPT in patients with germ cell tumors undergoing BEP. However, discontinuation of bleomycin with BPT does not adversely influence the survival outcomes.

DOI： 10.1007/s12032-018-1140-5

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Clinical impact of abdominal fat distribution using 3-D computed tomography volumetry on renal function after renal transplantation

Mitsui Y, Sadahira T, Maruyama Y, Takamoto A, Wada K, Tanimoto R, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y

The Journal of Urology 199 ( 4S ) e831 2018.4

Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with germ cell tumors

Maruyama Y, Sadahira T, Mitsui Y, Araki M, Wada K, Tanimoto R, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

Med Oncol 35 ( 6 ) 453 - 458 2018.4

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Papers - NASU Yasutomo