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恵谷 俊紀エタニ トシキ

所属部署医学研究科腎・泌尿器科学分野
職名助教
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Last Updated :2020/06/02

研究者基本情報

所属学協会

  • 日本泌尿器腫瘍学会
  • 日本泌尿器内視鏡学会
  • 日本性感染症学会
  • 日本環境感染学会
  • 日本緩和医療学会
  • 日本癌治療学会
  • 日本癌学会
  • 日本泌尿器科学会

研究活動情報

研究キーワード

    エピゲノム, 緩和医療, 尿路感染症, 泌尿器科腫瘍

論文

  • NCL1, A Highly Selective Lysine-Specific Demethylase 1 Inhibitor, Suppresses Castration-Resistant Prostate Cancer Growth via Regulation of Apoptosis and Autophagy., Toshiki Etani, Taku Naiki, Aya Naiki-Ito, Takayoshi Suzuki, Keitaro Iida, Satoshi Nozaki, Hiroyuki Kato, Yuko Nagayasu, Shugo Suzuki, Noriyasu Kawai, Takahiro Yasui, Satoru Takahashi, Journal of clinical medicine, 8, (4) ,   2019年03月31日, 査読有り, Recent studies have shown that epigenetic alterations lead to oncogenic activation, thus indicating that these are therapeutic targets. Herein, we analyzed the efficacy and therapeutic potential of our developed histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in castration-resistant prostate cancer (CRPC). The CRPC cell lines 22Rv1, PC3, and PCai1CS were treated with NCL1, and LSD1 expression and cell viability were assessed. The epigenetic effects and mechanisms of NCL1 were also evaluated. CRPC cells showed strong LSD1 expression, and cell viability was decreased by NCL1 in a dose-dependent manner. Chromatin immunoprecipitation analysis indicated that NCL1 induced histone H3 lysine 9 dimethylation accumulation at promoters of P21. As shown by Western blot and flow cytometry analyses, NCL1 also dose-dependently induced caspase-dependent apoptosis. The stimulation of autophagy was observed in NCL1-treated 22Rv1 cells by transmission electron microscopy and LysoTracker analysis. Furthermore, WST-8 assay revealed that the anti-tumor effect of NCL1 was reinforced when autophagy was inhibited by chloroquine in 22Rv1 cells. Combination index analysis revealed that a concurrent use of these drugs had a synergistic effect. In ex vivo analysis, castrated nude mice were injected subcutaneously with PCai1 cells and intraperitoneally with NCL1. Tumor volume was found to be reduced with no adverse effects in NCL1-treated mice compared with controls. Finally, immunohistochemical analysis using consecutive human specimens in pre- and post-androgen deprivation therapy demonstrated that LSD1 expression levels in CRPC, including neuroendocrine differentiation cases, were very high, and identical to levels observed in previously examined prostate biopsy specimens. NCL1 effectively suppressed prostate cancer growth in vitro and ex vivo without adverse events via the regulation of apoptosis and autophagy, suggesting that NCL1 is a potential therapeutic agent for CRPC.
  • Long-term survival of a patient with pulmonary metastatic urothelial carcinoma following metastasectomy., Hasebe K, Naiki T, Oda R, Etani T, Iida K, Sugiyama Y, Nozaki S, Ando R, Kawai N, Nakanishi R, Yasui T, Urology case reports, 21, 52 - 55,   2018年11月, 査読有り
  • GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis., Taku Naiki, Aya Naiki-Ito, Keitaro Iida, Toshiki Etani, Hiroyuki Kato, Shugo Suzuki, Yoriko Yamashita, Noriyasu Kawai, Takahiro Yasui, Satoru Takahashi, Oncotarget, 9, (22) 15847 - 15859,   2018年03月23日, 査読有り, Herein, we elucidated the molecular mechanisms and therapeutic potential of glutathione peroxidase 2 (GPX2) in bladder cancer. GPX2 expression gradually increased during progression from normal to papillary or nodular hyperplasia (PNHP) and urothelial carcinoma (UC) in a rat N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis model. GPX2 overexpression was more marked in UC with squamous differentiation (SqD) than in pure UC. Clinical intraepithelial lesions of papillary UC and invasive UC with SqD also had strong GPX2 expression in human radical cystectomy specimens. In addition, prognostic analysis using transurethral specimens revealed that low expression level of GPX2 predicted poor prognosis in patients with pure UC. Further, UC cell lines, BC31 and RT4, cultured in vitro also overexpressed GPX2. Knock-down of GPX2 induced significant inhibition of intracellular reactive oxygen species (ROS) production, in addition to significant growth inhibition and increased apoptosis with activation of caspase 3 or 7 in both BC31 and RT4 cells. Interestingly, tumor growth of BC31 cells subcutaneously transplanted in nude mice was significantly caused the induction of apoptosis, as well as inhibition of angiogenesis and SqD by GPX2 down-regulation. Our findings demonstrated that GPX2 plays an important role in bladder carcinogenesis through the regulation of apoptosis against intracellular ROS, and may be considered as a novel biomarker or therapeutic target in bladder cancer.
  • Early abiraterone acetate treatment is beneficial in Japanese castration-resistant prostate cancer after failure of primary combined androgen blockade., Nagai T, Naiki T, Iida K, Etani T, Ando R, Hamamoto S, Sugiyama Y, Akita H, Kubota H, Hashimoto Y, Kawai N, Yasui T, Prostate international, 6, (1) 18 - 23,   2018年03月, 査読有り
  • A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma., Naiki T, Iida K, Kawai N, Etani T, Ando R, Nagai T, Tanaka Y, Hamamoto S, Hamakawa T, Akita H, Sugiyama Y, Yasui T, Journal of rural medicine : JRM, 12, (2) 105 - 111,   2017年11月, 査読有り
  • Antimicrobial susceptibility of pathogens in acute uncomplicated cystitis cases in the urology department of a community hospital in Japan: Comparison with treatment outcome and hospital-wide antibiogram, Toshiki Etani, Taku Naiki, Sachiyo Yamaguchi, Saori Mori, Takashi Nagai, Keitaro Iida, Ryosuke Ando, Noriyasu Kawai, Keiichi Tozawa, Tohru Mogami, Takahiro Yasui, JOURNAL OF INFECTION AND CHEMOTHERAPY, 23, (10) 692 - 697,   2017年10月, 査読有り, We hypothesized that cases of uncomplicated cystitis treated in a Urology Department would display higher antimicrobial susceptibility than those reported by the hospital antibiogram. This would suggest narrow spectrum antibiotics could still be an effective treatment for uncomplicated cystitis despite this era of antimicrobial resistance. The objective of this study was thus to evaluate the rates of antimicrobial susceptibility of isolates cultured from uncomplicated cystitis cases that presented to the Urology Department of a community hospital in Japan. We evaluated the efficacy of cefaclor, a narrow spectrum antibiotic, for uncomplicated cystitis. We further compared the rates of antimicrobial susceptibility of isolates from uncomplicated cystitis cases to those reported in a hospital-wide antibiogram. A retrospective chart review was performed of patients diagnosed with uncomplicated cystitis in the Urology Department. The patients were mainly treated orally by cefaclor at 750 mg/day for seven days. Significantly greater susceptibilities to cefazolin (87.0% vs 65.7%), trimethoprim-sulfamethoxazole (89.4% vs 79.1%) and levofloxacin (84.6% vs 66.9%) were observed in a cystitis antibiogram for Escherichia coli compared with a hospital-wide antibiogram. The clinical efficacy of cefaclor for acute cystitis was also demonstrated. The greater susceptibility of Escherichia coli to antimicrobials observed in this study supports the hypothesis that antimicrobial susceptibility rates in uncomplicated cystitis cases that present to the Urology Department would be greater than those reported in the hospital antibiogram. Therefore, uncomplicated acute cystitis can be treated by narrow spectrum antibiotics such as cefaclor even in this "antimicrobial resistance era''. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
  • Metastatic urothelial carcinoma with glandular differentiation that confirmed the response by autopsy specimen to second-line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin) plus bevacizumab chemotherapy, Naiki, T., Etani, T., Naiki-Ito, A., Fujii, K., Ando, R., Iida, K., Nagai, T., Sugiyama, Y., Nakagawa, M., Kawai, N., Yasui, T., Case Reports in Oncology, 10, (3) 1057 - 1064,   2017年, 査読有り
  • Treatment Strategy for Pediatric Paratesticular Rhabdomyosarcoma Based on Chimeric Gene Assessment, Rei Unno, Kentaro Mizuno, Yasuhiko Ito, Toshiki Etani, Atsushi Okada, Noriyasu Kawai, Takahiro Yasui, Shinji Saitoh, Yutaro Hayashi, UROLOGY, 95, 187 - 189,   2016年09月, 査読有り, Rhabdomyosarcoma (RMS), a malignant tumor of the soft tissue, occurs in two major subtypes: embryonal and alveolar. A majority of pediatric RMS cases involve the embryonal type and occur in the soft tissues of the head and neck or the urogenital organs, which contain paratesticular tissues. We report herein two cases of pediatric paratesticular RMS. One case was embryonal, whereas the other case was alveolar; the latter exhibited PAX7-FOXO1 gene chimerism and rapid progression. Notably, this is the first report of pediatric paratesticular pure-type alveolar RMS in Japan. (C) 2016 Elsevier Inc.
  • Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: a case report., Iwatsuki S, Naiki T, Kawai N, Etani T, Iida K, Ando R, Nagai T, Okada A, Tozawa K, Sugiyama Y, Yasui T, Journal of medical case reports, 10, (1) ,   2016年05月, 査読有り
  • Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder., Nagai T, Naiki T, Kawai N, Iida K, Etani T, Ando R, Hamamoto S, Sugiyama Y, Okada A, Mizuno K, Umemoto Y, Yasui T, Case reports in oncology, 9, (1) 188 - 194,   2016年01月, 査読有り
  • Inflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report, Etani, T., Naiki, T., Nagai, T., Iida, K., Ando, R., Naiki-Ito, A., Kawai, N., Tozawa, K., Mizuno, K., Okada, A., Mogami, T., Yasui, T., Case Reports in Oncology, 9, (2) 464 - 469,   2016年, 査読有り

MISC

  • 高齢の転移性尿路上皮癌患者に対する2nd line GD療法の検証, 内木 拓, 飯田 啓太郎, 惠谷 俊紀, 田中 勇太朗, 濱川 隆, 安藤 亮介, 河合 憲康, 安井 孝周, 永井 隆, 岡村 武彦, 永田 大介, 泌尿器科紀要, 64, (5) 242 - 242,   2018年05月
  • エピゲノム変化を介した去勢抵抗性前立腺癌におけるオートファジー制御メカニズムの解明と新規治療法の開発, 惠谷 俊紀, 内木 拓, 内木 綾, 飯田 啓太郎, 安藤 亮介, 河合 憲康, 高橋 智, 鈴木 孝禎, 安井 孝周, 日本泌尿器科学会総会, 106回,   2018年04月
  • ルテオリンの膀胱がん抑制メカニズムの解明, 飯田 啓太郎, 内木 拓, 内木 綾, 田中 祐太郎, 惠谷 俊紀, 安藤 亮介, 河合 憲康, 高橋 智, 安井 孝周, 日本泌尿器科学会総会, 106回,   2018年04月
  • 前立腺癌発症とインスリン抵抗性に関する前向きコホート研究, 安藤 亮介, 鈴木 貞夫, 細野 晃弘, 山田 珠樹, 田中 勇太朗, 飯田 啓太郎, 惠谷 俊紀, 内木 拓, 河合 憲康, 戸澤 啓一, 安井 孝周, 日本泌尿器科学会総会, 106回,   2018年04月
  • Real-time Virtual Sonography(RVS)システムを用いたMR-TRUS同期前立腺生検の検討, 永井 隆, 内木 拓, 濱本 周造, 田中 勇太朗, 飯田 啓太郎, 惠谷 俊紀, 安藤 亮介, 河合 憲康, 小林 大地, 小林 隆宏, 秋田 英俊, 岡村 武彦, 安井 孝周, 日本泌尿器科学会総会, 106回,   2018年04月
  • 臍マルチチャネルポートReduce port 腹腔鏡下腎尿管膀胱全摘除術/全尿路全摘除の経験, 田中 勇太朗, 秋田 英俊, 永井 隆, 小林 大地, 小林 隆宏, 岡村 武彦, 山田 健司, 飯田 啓太郎, 惠谷 俊紀, 内木 拓, 安藤 亮介, 河合 憲康, 安井 孝周, 日本癌治療学会学術集会抄録集, 55回,   2017年10月
  • 骨転移を有する去勢抵抗性前立腺患者に対する塩化ラジウム注射液の初期使用経験, 永井 隆, 岡村 武彦, 茶谷 亮輔, 小林 大地, 小林 隆宏, 秋田 英俊, 田中 勇太朗, 飯田 啓太郎, 惠谷 俊紀, 内木 拓, 安藤 亮介, 河合 憲康, 安井 孝周, 日本癌治療学会学術集会抄録集, 55回,   2017年10月
  • オピオイド内服中の患者における便秘症に対するルビプロストンの効果, 惠谷 俊紀, 杉山 洋介, 内木 拓, 田中 勇太朗, 永井 隆, 飯田 啓太郎, 河合 憲康, 最上 徹, 安井 孝周, 日本癌治療学会学術集会抄録集, 55回,   2017年10月
  • 泌尿器系腫瘍に対するIVR手技を用いたマグネタイト併用のRF-8温熱治療への挑戦, 河合 憲康, 永井 隆, 内木 拓, 飯田 啓太郎, 安藤 亮介, 惠谷 俊紀, 安井 孝周, Thermal Medicine, 33, (3) 91 - 91,   2017年10月
  • ヒストン脱メチル化酵素LSD1の新規阻害剤NCL1の前立腺癌に対する抗腫瘍効果, 惠谷 俊紀, 内木 拓, 飯田 啓太郎, 安藤 亮介, 河合 憲康, 戸澤 啓一, 鈴木 孝禎, 高橋 智, 安井 孝周, Nagoya Medical Journal, 55, (4) 169 - 174,   2017年08月, 本研究では、前立腺癌の新規治療標的として期待されるヒストン脱メチル化酵素LSD1の新規阻害剤であるNCL1の前立腺癌への効果を検証した。去勢感受性前立腺癌細胞株LNCaPおよび去勢抵抗性前立腺癌細胞株PC3およびPCailを用いて、LSD1の発現およびNCL1投与による生存細胞数の変化を検討したところ、いずれの前立腺癌細胞株においてもLSD1が発現しており、NCL1の投与によって濃度依存的に生存細胞数が抑制された。また、ヒト臨床検体を用いた解析でも、LSD1は高悪性度の前立腺癌ほど高発現しており、前立腺癌における新規治療標的となると考えられた。続いて、in vitroにおいてNCL1の効果のメカニズムの検討を行った。ChIP-qPCRアッセイでは、NCL1は増殖に関わる遺伝子のメチル化状態を変化させていることが示された。フローサイトメトリーおよびウェスタンブロットによる解析では、NCL1は前立腺癌細胞株にcell cycle arrestおよびアポトーシスを誘導していた。また、細胞生存に関わる防御反応で、癌の新規治療標的として期待されているオートファジーについて解析した。NCL1の投与によってオートファゴソームおよびオートリソソームが生じており、オートファジーのマーカーであるLC3-IIの誘導も認められた。オートファジー阻害剤であるクロロキンの併用によるNCL1の抗腫瘍効果の増強が認められ、NCL1とオートファジー阻害剤の併用療法の有用性が示された。さらに、生体内におけるNCL1の効果の検討のため、前立腺癌皮下移植モデルマウスにNCL1を投与したところ、腫瘍体積の増加が有意に抑制され、生体に対する明らかな有害事象は認めなかった。以上より、NCL1は前立腺癌に対する新規治療薬として有望と考えられた。(著者抄録)

受賞

  •   2017年04月, 一般社団法人日本泌尿器科学会, 第11回ヤングリサーチグラント
  •   2016年06月, 日本アンドロロジー学会, 日本アンドロロジー学会 学術奨励賞(基礎部門)
  •   2016年01月, 名古屋市立大学瑞川会, 岡賞
  •   2015年03月, 名古屋市立大学大学院医学研究科, 優秀論文賞
  •   2014年06月, 日本泌尿器科学会東海地方会, 第264回日本泌尿器科学会東海地方会 優秀発表賞


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