Project/Area Number |
20591543
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
|
Research Institution | Chiba University |
Principal Investigator |
MATSUSHITA Kazuyuki Chiba University, 大学院・医学研究院, 講師 (90344994)
|
Co-Investigator(Kenkyū-buntansha) |
朝長 毅 千葉大学, 大学院・医学研究院, 准教授 (80227644)
星野 忠次 千葉大学, 大学院・医学研究院, 准教授 (90257220)
田村 裕 千葉大学, 大学院・医学研究院, 准教授 (50263174)
野村 文夫 千葉大学, 大学院・医学研究院, 教授 (80164739)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 癌遺伝子治療 / c-myc遺伝子 / 癌診断 / 癌治療 / スプライシング阻害薬 / SF3b155 / 転写制御因子 / アポトーシス |
Research Abstract |
Far UpStream Element (FUSE)-binding protein-interacting repressor (FIR), a c-myc transcriptional suppressor, is alternatively spliced and futilely produced in colorectal cancer tissues that abundantly express c-Myc. Human malignant pleural mesothelioma (HMPM) is highly resistant to conventional therapy, and novel therapies are thus required. We previously reported that overexpression of FIR induces apoptosis via c-Myc suppression, and is thus a suitable cancer therapy. In the current preclinical trial, a fusion gene deleted non-transmissible Sendai virus vector encoding FIR (SeV/ΔF/FIR) was prepared and its cytotoxic activity against an orthotopic xenograft model of HMPM, in combination with cisplatin, was assessed. SeV/ΔF/FIR significantly reduced cell viability in 3 HMPM cell lines but was less effective in non-tumor immortalized mesothelial cells. SeV/ΔF/FIR cytotoxicity was partly due to apoptosis induction via c-Myc supression.
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