Therapeutic strategy for oxaliplatin-induced neuropathy by mulecular targeting drugs

• Project/Area Number: 25860071
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Kinki University
• Principal Investigator: TSUBAKI Masanobu 近畿大学, 薬学部, 講師 (30434856)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: オキサリプラチン / 末梢神経障害 / 分子標的薬 / 抑制薬 / PKC / ERK / シグナル伝達因子

Outline of Final Research Achievements

I show that oxaliplatin induces the neuropathy through the activation of PKC/ERK/c-Fos pathway in lumber spinal cords. In addition, PKC inhibitor suppressed the oxaliplatin-induced neuropathy via PKC pathways. These findings suggest that PKC inhibitors are potentially useful for oxaliplatin-induced neuropathy.
As well, These results are summarized as section of presented paper.

Research Products

• [Journal Article] RANK-RANKL interactions are involved in cell adhesion-mediated drug resistance in multiple myeloma cell lines. (2016)
  • Author(s): Tsubaki M, Takeda T, Yoshizumi M, Ueda E, Itoh T, Imano M, Satou T, Nishida S.
  • Journal Title: Tumour Biol. Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PKC/MEK inhibitors suppress oxaliplatin-induced neuropathy and potentiate the antitumor effects. (2015)
  • Author(s): Tsubaki M, Takeda T, Tani T, Shimaoka H, Suzuyama N, Sakamoto K, Fujita A, Ogawa N, Itoh T, Imano M, Funakami Y, Ichida S, Satou T, Nishida S.
  • Journal Title: Int J Cancer. Volume: In press Issue: 1 Pages: 243-250
  • DOI: 10.1002/ijc.29367
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mangiferin suppresses CIA by suppressing the expression of TNF-α, IL-6, IL-1β, and RANKL through inhibiting the activation of NF-κB and ERK1/2. (2015)
  • Author(s): Tsubaki M, Takeda T, Kino T, Itoh T, Imano M, Tanabe G, Muraoka O, Satou T, Nishida S.
  • Journal Title: Am J Transl Res. Volume: 7 Pages: 1371-1381
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Statins improve survival by inhibiting spontaneous metastasis and tumor growth in a mouse melanoma model. (2015)
  • Author(s): Tsubaki M, Takeda T, Kino T, Obata N, Itoh T, Imano M, Mashimo K, Fujiwara D, Sakaguchi K, Satou T, Nishida S.
  • Journal Title: Am J Cancer Res. Volume: 5 Pages: 3186-3197
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] PKC及びMEK阻害剤によるオキサリプラチン誘発末梢神経障害の抑制及び抗腫瘍効果の増強. (2016)
  • Author(s): 椿 正寛、武田 朋也、木野 稔己、藤原 大一朗、山添 譲、阪口 勝彦、西田 升三.
  • Organizer: 日本薬学会第136回年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2016-03-27
• [Presentation] PKC 阻害剤はオキサリプラチン誘発末梢神経障害を抑制し抗腫瘍効果を増強させる. (2015)
  • Author(s): 安原 翔大、椿 正寛、武田 朋也、西田 升三.
  • Organizer: 第65回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪大谷大学（大阪府）
  • Year and Date: 2015-10-17
• [Presentation] PKC 阻害剤はオキサリプラチン誘導末梢神経障害を抑制するとともに抗腫瘍効果を増強させる. (2015)
  • Author(s): 椿 正寛、武田 朋也、中橋 拓也、小川 直希、石坂 敏彦、西田 升三.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2015-10-08
• [Presentation] PKC/MEK阻害剤によりoxaliplatin誘導末梢神経障害を抑制できる. (2015)
  • Author(s): 椿 正寛、武田 朋也、藤田 亜梨沙、木野 稔己、中橋 拓也、小川 直希、山添 譲、石坂 敏彦、西田 升三.
  • Organizer: 第19回日本がん分子標的治療学会
  • Place of Presentation: 松山全日空ホテル（愛媛県）
  • Year and Date: 2015-06-10