DNA mismatch repair gene analysis predicts the response to anticancer drug sensitivity in gastrointestinal cancers for tailored therapy.

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390321
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kobe University
• Principal Investigator: Kakeji Yoshihiro 神戸大学, 医学(系)研究科(研究院), 教授 (80284488)
• Co-Investigator(Kenkyū-buntansha): KITAO Hiroyuki 九州大学, 大学院医学研究科, 准教授 (30368617) ; IIMORI Makoto 九州大学, 大学院医学研究科, 助教 (20546460) ; SAEKI Hiroshi 九州大学, 大学院医学研究科, 准教授 (80325448) ; TOKUNAGA Eriko 九州がんセンター, 臨床研究センター, 部長 (50325453) ; OKI Eiji 九州大学, 大学病院, 講師 (70380392) ; MAEHARA Yoshihiko 九州大学, 大学院医学研究科, 教授 (80165662) ; MORITA Masaru 九州がんセンター, 臨床研究センター, 部長 (30294937)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 胃十二指腸外科学 / 5-FU感受性 / DNA修復系関連遺伝子

Outline of Final Research Achievements

1.In vitro, Fanconi anemia protein, FANCJ overexpression was correlated with 5-FU resistance in MLH1 proficient HCT116 3-6 cells but not in MLH1-deficient HCT116 cells. FANCJ could be a useful biomarker to predict the response to 5-FU and prognosis of CRC, particularly in tumors with normal MLH1 expression.
2.Although numerous ssDNA and dsDNA breaks were induced by FdUrd, few DNA strand breaks were detected in Trifluridine (FTD)-treated HCT-116 cells despite massive FTD misincorporation into genomic DNA, suggesting that the antiproliferative effect of FTD is not due to the induction of DNA strand breaks.
3.The diaminocyclohexane (DACH) carrier ligand in oxaliplatin triggers signaling via the p53-miR-34a-E2F axis, leading to transcriptional regulation that ultimately results in accumulation of deoxyuridine triphosphate (dUTP) and reduced thymidine triphosphate (dTTP) biosynthesis, potentially enhancing 5-FU cytotoxicity.

Free Research Field

消化器外科学