Therapeutic strategy targeting NFκB-IL6 pathway against progression and paraneoplastic syndrome in prostate cancer

• Project/Area Number: 22591779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Tokyo Medical University
• Principal Investigator: NAKASHIMA Jun 東京医科大学, 医学部, 教授 (10167546)
• Co-Investigator(Kenkyū-buntansha): TACHIBANA Masaaki 東京医科大学, 医学部, 教授 (70129526)
• Co-Investigator(Renkei-kenkyūsha): HORIGUCHI Yutaka 東京医科大学, 医学部, 准教授 (60229234) ; OHNO Yoshio 東京医科大学, 医学部, 准教授 (40266482)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腫瘍学 / 前立腺癌 / NFκB / 内分泌治療 / 放射線治療 / NF-κB / NFkappaB / cell cycle / docetaxel

Research Abstract

This study was undertaken to elucidate the pathophysiological role of NFκB－IL6 pathway and antitumor effects of NF κB inhibitors including dihydroxymethylepoxyquinomicin (DHMEQ) in prostate cancer. DHMEQ showed significant cytotoxic effects on prostate cancer cells in dose dependent and time dependent manners, produced a significant increase in G2/M arrest in the cell cycle and enhanced the cytotoxic effects of docetaxel on prostatecancer cells. DHMEQ significantly enhanced cytotoxic effects of radiation on prostate cancer, presumably through inhibiting the increased NFκB activity induced by radiation and enhancing the proportion of G2/M arrest in the cells in combination with radiation. Inhibition of NFκB activity may become a new therapeutic modality for treating prostate cancer.

Research Products

• [Journal Article] A Prospective Longitudinal Survey of Erectile Dysfunction in Patients with Localized Prostate Cancer Treated with Permanent Prostate Brachytherapy (2013)
  • Author(s): Matsushima M, Kikuchi E, Maeda T, Nakashima J, Sugawara A, Ando T, Mizuno R, Nagata H, Miyajima A, Shigematsu N, Oya M
  • Journal Title: J Urol Volume: 189(3) Pages: 1014-1018
  • Peer Reviewed
• [Journal Article] Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer. (2012)
  • Author(s): Kozakai N, Kikuchi E, Hasegawa M, Suzuki E, Ide H, Miyajima A, Horiguchi Y,Nakashima J, Umezawa K, Shigematsu N, Oya M
  • Journal Title: Br J Cancer. Volume: 107(4) Pages: 652-7
  • Peer Reviewed
• [Journal Article] Enhancement of radiosensitivity by a unique novel NF-kB inhibitor, DHMEQ, in prostate cancer (2012)
  • Author(s): Kozakai N.
  • Journal Title: British Journal of Cancer Volume: 107(4) Pages: 652-7
  • Peer Reviewed
• [Journal Article] ホルモン治療が施行された進行性前立腺癌の予後因子の検討 (2011)
  • Author(s): 下平憲治、中島淳、大堀理、小津兆一郎、 大野芳正 、堀口裕 、並木一典、吉岡邦彦、秦野直、橘政昭
  • Journal Title: 泌尿器外科 Volume: 24(8) Pages: 1381-1383
• [Journal Article] Incidence of seed migration to the chest, abdomen, and pelvis after transperineal interstitial prostate brachytherapy with loose 125I seeds. (2011)
  • Author(s): Sugawara A, Nakashima J, Kunieda E, Nagata H, Mizuno R, Seki S, Shiraishi Y, Kouta R, Oya M, Shigematsu N
  • Journal Title: Radiat Oncol Volume: 6(1) Pages: 130-130
  • Peer Reviewed
• [Journal Article] 進行前立腺癌に対する新戦略。NF-κB 阻害剤 (2011)
  • Author(s): 中島淳、 堀口裕、 大野芳正、権藤立男、竹内尚史、橘政昭
  • Journal Title: 日本臨床 Volume: 69 Pages: 160-164
• [Journal Article] 進行前立腺癌に対する新戦略NF-κB阻害剤 (2011)
  • Author(s): 中島淳、堀口裕、大野芳正、権藤立男、竹内尚史、橘政昭
  • Journal Title: 日本臨床 Volume: 69巻 Pages: 160-164
• [Presentation] P r e d i c t i o n o f leukopenia after docetaxel chemotherapy in patients with castration-resistant prostate cancer (2012)
  • Author(s): Jun Nakashima, Issei Takizawa , Kazuyoshi Ko, Yoshihiro Nakagami, Makoto Ohori, Yoshio Ohno, Kunihiko Yoshioka, Masaaki Tachibana
  • Organizer: American Urological Associaiton 2012 annual meeting
  • Place of Presentation: Atlanta(米国)
• [Presentation] 去勢抵抗前立腺癌におけるドセタキセル治療後の PSA 値の検討。 (2012)
  • Author(s): 黄和吉, 中島淳, 中神義弘, 大堀理, 小津兆一郎, 大野芳正, 堀口裕, 並木一典, 吉岡邦彦, 秦野直, 橘政昭
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 横浜
• [Presentation] 去勢抵抗性前立腺癌に対する治療戦略。 (2011)
  • Author(s): 中島淳
  • Organizer: 泌尿器癌カンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2011-11-10
• [Presentation] 特別講演「去勢抵抗性前立腺癌に対する治療戦略」 (2011)
  • Author(s): 中島淳
  • Organizer: 前立腺癌座談会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-24
• [Presentation] 内分泌治療が施行された進行性前立腺癌の予後因子の検討 (2011)
  • Author(s): 下平憲治, 中島淳, 大堀理, 小津兆一郎, 大野芳正, 堀口裕, 並木一典, 吉岡邦彦, 秦野直, 橘政昭
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-04-21
• [Presentation] High risk 限局性前立腺癌における根治術後の PSA 再発を予測する術前因子の検討。 (2011)
  • Author(s): 濱田理宇, 中島淳, 大堀理, 小津兆一郎, 大野芳正, 並木一典, 堀口裕, 吉岡邦彦, 秦野直, 井上理恵, 船橋健二郎, 池田龍介, 橘政昭
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-04-21
• [Presentation] 早期前立腺癌に対する密封小線源永久挿入治療後の D90 の検討 (2011)
  • Author(s): 中島淳, 菅原章友, 水野隆一, 長田浩彦, 鹿島剛, 大久保秀紀, 下平憲治, 橋本剛, 伊関亮, 大堀理, 茂松直之, 大家基嗣, 橘政昭
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-04-21
• [Presentation] 骨痛のある再燃前立腺癌におけるドセタキセル療法の意義 (2010)
  • Author(s): 中神義弘、大堀理、橋本剛、井関亮、中島淳、秦野直、橘政昭
  • Organizer: 第26回前立腺シンポジウム
  • Place of Presentation: 東京