| Project/Area Number |
22791305
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | ミトコンドリアDNA / 体細胞変異 / 消化器癌 / 抗癌剤耐性 / 転移・浸潤 |
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| Research Abstract |
We showed that mutations in mitochondrial DNA (mtDNA: derived from pancreatic cancer, gastric cancer and colorectal cancer cell lines) are responsible for anticancer drug tolerance(5FU, CDDP, CPT-11, Gemcitabine) in vitro and in vivo with trans-mitochondrial hybrids(cybrids) technique.
We used trans-mitochondrial hybrid cells (cybrids) to reveal the role of mutations in mtDNA in the pancreatic cancer by excluding any effects of the nuclear background. Cybrids were constructed by repopulating HeLa devoid of mtDNA with mtDNA derived from enucleated the pancreatic cancer, gastric cancer and colorectal cancer cell lines sharboring mtDNA mutations. We constructed several cybrids with mutations derived from the cancer cells as well as those with wild mtDNA derived healthy individuals, and transplanted mutant and wild type cybrids into nude mice to generate tumors. We compared tumor growth and massive apoptosis of mutant cybrid tumors to wild cybrid tumors administrated of 5FU, CDDP, CPT-11, Gemcitabine. All experiments were performed in accordance with the guidelines of the Animal Use Ethics Committee of Nippon Medical School.
Result:Tumors derived from mutant cybrids were more resistant than those from wild-type cybrids in suppressing tumor growth and inducing massive apoptosis when the all of anti-cancerdrugs were administered.
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