| Project/Area Number |
21591768
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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 |
Digestive surgery
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAI Yoshio 新潟大学, 医歯学系, 准教授 (50216173)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 胆道外科学 / 胆管癌 / 胆管切離断端 / p53-binding protein 1 / DNA損傷修復応答 / 上皮内癌 / アポトーシス / 53-binding protein 1 |
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| Research Abstract |
This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. Ductal margin status was the only independent risk factor for local recurrence(P=0. 001). The cumulative probability of local recurrence at 5 years was 10%, 40%, and 100% in patients with negative ductal margins, positive with carcinoma in situ, and positive with invasive carcinoma, respectively(P<0. 001). Of the 14 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei(53BP1 inactivation) and 4 showed discrete nuclear foci of 53BP1(53BP1 activation). Apoptotic index was markedly decreased in tumor specimens with 53BP1 inactivation compared to those with 53BP1 activation(median index, 0% vs. 22%; P<0. 001). Among 14 patients with residual carcinoma in situ, the cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation(60% vs. 0% at 5 years ; P=0. 020). In conclusion, after resection for extrahepatic cholangiocarcinoma, clinically evident local recurrence at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.
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