2005 Fiscal Year Final Research Report Summary
Molecular significance of neo-adjuvant chemoradiotherapy for rectal cancer
| Project/Area Number |
16591252
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Mie University |
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Principal Investigator |
KUSUNOKI Masato Mie University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50192026)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Yasuhiro Mie University, Graduate School of Medicine, Assistant Professor, 医学部附属病院, 助手 (20324535)
HATADA Tuyoshi Mie University, Mie University Hospital, Assistant Professor, 医学部附属病院, 助手 (20345987)
MIKI Chikao Mie University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50242962)
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| Project Period (FY) |
2004 – 2005
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| Keywords | rectal cancer / radiation / sensitivity / microarray / 5-FU |
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| Research Abstract |
Effectiveness of gene expression profiling for response prediction of rectal cancer to preoperative radiotherapy ;
We established the radiation resistant colorectal cancer cell line and compared the gene expression parent and resistant cell line using microarray system. 17 up-regulated and 142 down-regulated genes were characteristics in resistant cell lines. Next, we confirmed this microarray data in human samples by RT-PCR. The expression of PTMA, a nuclear protein involved in cell proliferation, was significantly higher at clinical radioresistant group. Thus PTMA could be a novel marker predicting effectiveness of radiotherapy in clinical cases.
The optimal schedule for 5-FU radiosensitization in colon cancer cell line ;
Next, we investigated the interaction between radiation and several doses of 5-FU on colon cancer cell lines based on pharmacokinetics of oral fluoropyrimidine. 5-FU doses were classified into three groups : uracil-tegafur (0.01-0.1μM), S-1 (0.1-1.0 μM) and pharmacokinetic modulating chemotherapy (0.1-10μM) according to our previous report. In addition, the effect of 5-FU on the steady-state levels of a human excision repair cross-complementing 1 gene and cell cycle distribution were examined. In conclusion, oral fluoropyrimidines, like S-1, that can maintain a constant level of 5-FU may be an acceptable alternative radiosensitizer to protracted 5-FU infusion.
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