Establishment of the optimal administration method for anticancer agents by proteomics and metabolomics

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kobe University
• Principal Investigator: MINAMI Hironobu 神戸大学, 医学(系)研究科(研究院), 教授 (60450574)
• Co-Investigator(Kenkyū-buntansha): MUKOUHARA Toru 神戸大学, 医学部附属病院, 特命准教授 (80435718) ; YOSHIDA Masaru 神戸大学, 大学院医学研究科, 准教授 (00419475)
• Project Period (FY): 2011 – 2013
• Keywords: 乳がん / 化学療法 / 末梢神経毒性 / 抗腫瘍効果 / プロテオーム解析 / パクリタキセル

Research Abstract

Proteomics was investigated to identify proteins which were associated with efficacy and toxicities of the primary systemic chemotherapy with weekly paclitaxel in patients with early breast cancer. Paclitaxel was given at 80 mg/m2, and plasma was obtained before the treatment and 6-8 days after the first administration of paclitaxel. Toxicities were monitored weekly. Among 20 patients, good PR was achieved in 4 and grade 2 or greater peripheral neuropathy was observed in 9. The greatest difference between responders and non-responders was observed in concentrations of Fibulin-1, and Dynein heavy chain 7 showed the greatest correlation to peripheral neuropathy. Patients with a lower concentration of Dynein heavy chain 7 was associated with a higher risk of peripheral neuropathy, and its concentration was increased after the start of the treatment in 5 of 7 patients who experienced neuropathy. Fibulin-1 was also significantly associated with peripheral neuropathy.

Research Products

• [Journal Article] Pathologic complete response after neoadjuvant chemotherapy in HER2-overexperssing breast cancer according to hormonal receptor status (2014)
  • Author(s): Tanioka M, Sasaki M, Shimomura A, Fujishima M, Doi M, Matsuura K, Sakuma T, Yoshimura K, Saeki T, Ohara M, Tsurutani J, Watatani M, Takano T, Kawabata H, Mukai H, Naito Y, Hirokaga K, Takao S, Minami H
  • Journal Title: Breast(Epub)
  • DOI: 10.1016/j.breast.2014.03.008
  • Peer Reviewed
• [Journal Article] Barriers and challenges to global clinical cancer research (2014)
  • Author(s): Seruga B, Sadikov A, Cazap EL, Delgado LB, Digumarti R, Leighl NB, Meshref MM, Minami H, Robinson E, Yamaguchi NH, Pyle D, Cufer T
  • Journal Title: Oncologist Volume: 19(1) Pages: 61-7
  • Peer Reviewed
• [Journal Article] Excessive MET signaling causes acquired resistance and addiction to MET inhibitors in the MKN45 gastric cancer cell line (2013)
  • Author(s): Funakoshi Y, Mukohara T, Tomioka H, Ekyalongo RC, Kataoka Y, Inui Y, Kawamori Y, Toyoda M, Kiyota N, Fujiwara Y, Minami H
  • Journal Title: Invest New Drugs Volume: 31 (5) Pages: 1158-68
  • Peer Reviewed
• [Journal Article] A novel serum metabolomics-based diagnostic approach to pancreatic cancer (2013)
  • Author(s): Kobayashi T, Nishiumi S, Ikeda A, Yoshie T, Sakai A, Matsubara A, Izumi Y, Tsumura H, Tsuda M, Nishisaki H, Hayashi N, Kawano S, Fujiwara Y, Minami H, Takenawa T, Azuma T, Yoshida M
  • Journal Title: Cancer Epidemiology Biomarkers & Prevention Volume: 22 Pages: 571-579
  • Peer Reviewed
• [Journal Article] Mechanisms of acquired resistance to insulin-like growth factor 1 receptor inhibitor in MCF-7 breast cancer cell line (2013)
  • Author(s): Ekylongo RC, Mukohara T, Kataoka Y, Kiyota N, Fujiwara Y, Minami H
  • Journal Title: Invest New Drugs Volume: 31 Pages: 293-303
  • Peer Reviewed
• [Journal Article] Inhibition of the mTOR/S6K signal is necessary to enhance fluorouracil-induced apoptosis in gastric cancer cells with HER2 amplification (2012)
  • Author(s): Tomioka H, Mukohara T, Kataoka Y, Ekyalongo RC, Funakoshi Y, Imai Y, Kiyota N, Fujiwara Y, Minami H
  • Journal Title: Int J Oncol Volume: 41 Pages: 551-558
  • Peer Reviewed
• [Journal Article] Eribulin mesylate in patients with refractory cancers:a phase I study (2012)
  • Author(s): Mukohara T, Nagai S, Mukai H, Namiki M, Minami H.
  • Journal Title: Invest New Drugs Volume: 30 (5) Pages: 1926-1933
  • Peer Reviewed
• [Journal Article] Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks (2012)
  • Author(s): Kataoka Y, Mukohara T, Tomioka H, Funakoshi Y, Kiyota N, Fujiwara Y, Yashiro M, Hirakawa K, Hirai M, Minami H
  • Journal Title: Invest New Drugs Volume: 30 (4) Pages: 1352-1360
  • Peer Reviewed
• [Presentation] 乳癌における新規治療標的としてのTyro3 (2013)
  • Author(s): Ekylongo Roudy Chiminch、向原徹、船越洋平、富岡秀夫、片岡優、豊田昌徳、清田尚臣、南博信
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] HER2陽性ホルモン受容体陽性(HR+)乳癌における術前科学療法後病理学的完全寛解(pCR)の臨床的意義 (2013)
  • Author(s): 谷岡真樹、佐々木正興、下村昭彦、藤島茂、土井美帆子、松浦一生、吉村健一、内藤陽一、高尾信太郎、南博信
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 20130829-31
• [Presentation] Excessive MET signaling causes acquired resistance to and addiction to METinhibitors MET-amplifed cancer cellline (2013)
  • Author(s): 船越洋平、向原徹、富岡秀夫、Ekylongo Roudy Chiminch、片岡優、豊田昌徳、清田尚美、藤原豊、南博信
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 20130829-31
• [Presentation] Excessive MET signaling causes acquired resistance to and addiction to MET inhibitors in MKN45 gastric cancer cell line (2012)
  • Author(s): Funakoshi Y, Mukohara T, Tomioka H, Ekyalonog RC, Kataoka Y, Inui Y, Kawamori Y, Kiyota N, Fujiwara Y, Minami H
  • Organizer: 24rh EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 20121106-09
• [Presentation] MCF-7乳癌細胞株におけるinsuylin-like growth factor 1 receptor受容体阻害薬に対する獲得耐性機構 (2012)
  • Author(s): Ekylongo Roudy Chiminch、向原徹、片岡優、船越洋平、富岡秀夫、清田尚臣、藤原豊、南博信
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21