Comprehensive cancer therapy targeted Nek2 and translational research

2012 Fiscal Year Final Research Report

• Project/Area Number: 20249062
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: NIMURA Yuji 愛知県がんセンター(研究所), 名誉総長 (80126888)
• Co-Investigator(Kenkyū-buntansha): SANO Tsuyoshi 愛知県がんセンター(研究所), 腫瘍病理学部, 研究員 (60303632) ; ABE Tetsuya 愛知県がんセンター(研究所), 疫学・予防部, 研究員 (90378092) ; NAGINO Masato 名古屋大学, 医学(系)・研究科(研究院), 教授 (20237564) ; YOKOYAMA Yukihiro 名古屋大学, 医学部・附属病院, 講師 (80378091) ; KOKURYOU Toshio 名古屋大学, 医学(系)・研究科(研究院), 講師 (60378023) ; SENGA Takeshi 名古屋大学, 医学部・附属病院, 講師 (80419431)
• Project Period (FY): 2008 – 2012
• Keywords: NeK2 / 分子標的治療 / トランスレーショナルリサーチ

Research Abstract

The combination treatment using Nek2 siRNA and S1 suppressed the tumor growth in colorectal cancer model, more efficiently than Nek2 siRNA. The combined treatment of Nek2 siRNA with CDDP was also more effective than the administration of Nek2 siRNA alone. The combination exerted additive growth inhibition. The transmission of Nek2 siRNA to blood was the highest at 15 min and was less than 0.2μM (0.04% of doses). Nek2 siRNA disappeared within 1 h after the administration.
No abnormalities in blood tests were observed. The No Observed Adverse Effect Level (NOAEL：No Observed Adverse Effect Levels) was 3.7 (mg/kg). Based on the data, we decided the Maximum Recommended Starting Dose (MRSD) as 0.0285 (mg/kg).

Research Products

• [Journal Article] Effect of biliary drainage on chemotherapy in patients with biliary tract cancer: an exploratory analysis of the BT22 study (2012)
  • Author(s): Fukutomi A, Furuse J, Okusaka T, Miyazaki M, Taketsuna M, Koshiji M, Nimura Y.
  • Journal Title: HPB (Oxford) Volume: 14(4) Pages: 221-7
  • Peer Reviewed
• [Journal Article] Silencing of Tousled-like kinase 1 sensitizes cholangiocarcinoma cells to cisplatin-induced apoptosis. (2010)
  • Author(s): Takayama Y, Kokuryo T, Yokoyama Y, Ito S, Nagino M, Hamaguchi M, Senga T.
  • Journal Title: Cancer Lett. Volume: 296(1) Pages: 27-34
  • Peer Reviewed
• [Journal Article] Novel combination treatment for colorectal cancer using Nek2 siRNA and cisplatin (2010)
  • Author(s): Suzuki K, Kokuryo T, Senga T, Yokoyama Y, Nagino M, Hamaguchi M.
  • Journal Title: Cancer Sci. Volume: 101(5) Pages: 1163-1169
  • Peer Reviewed
• [Journal Article] Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. (2010)
  • Author(s): Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, Nagino M, Kondo S, Nagaoka S, Funai J, Koshiji M, Nambu Y, Furuse J, Miyazaki M, Nimura Y.
  • Journal Title: Br J Cancer. Volume: 103(4) Pages: 469-74
  • Peer Reviewed
• [Presentation] Nek2 siRNAの非臨床試験と臨床応用 (2012)
  • Author(s): 國料俊男, 横山幸浩, 江畑智希, 菅原 元, 高橋 祐, 伊神 剛, 深谷昌秀, 上原圭介, 板津慶太, 吉岡裕一郎, 梛野正人
  • Organizer: 第67回 日本消化器外科学会総会
  • Place of Presentation: 富山国際会議場(富山)
  • Year and Date: 2012-07-19
• [Presentation] The combination treatments using siRNA and CDDP are effective therapeutic options for cancers. (2012)
  • Author(s): T Kokuryo, Y Yokoyama, K Suzuki, T Ebata, N Tsunoda, T Igami, G Sugawara, M Fukaya, Y Takahashi, K Uehara, Y Yoshioka, M Nagino.
  • Organizer: AACR 102nd annual meeting
  • Place of Presentation: Orange County Convention Center (Orlando, USA)
  • Year and Date: 2012-04-04
• [Presentation] The efficiency of Nek2 siRNAfor liver metastasis of pancreatic cancer (2012)
  • Author(s): Kokuryo T, Yokoyama Y, Nagino M.
  • Organizer: AACR 103rd annual meeting
  • Place of Presentation: McCormick Place (Chicago, USA)
  • Year and Date: 2012-04-01
• [Presentation] siRNAを用いた癌分子標的治療のトランスレーショナルリサーチ (2010)
  • Author(s): 國料俊男、横山幸浩、梛野正人
  • Organizer: JDDW 2010
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2010-10-15
• [Presentation] Nek2 as an effective molecular target for cancer treatment. (2010)
  • Author(s): Kokuryo T, Senga T, Yokoyama Y, Nagino M, Hamaguchi M.
  • Organizer: AACR 101st annual meeting.
  • Place of Presentation: Walter E. Washington Convention Center (Washington DC, USA)
  • Year and Date: 2010-04-19