| Project/Area Number |
22791268
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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 | University of Yamanashi |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 食道扁平上皮癌 / 抗体療法 / trastuzumab / Herceptin / 細胞障害活性 / 抗体依存性細胞障害 / ADCC / perforin / granzyme |
|---|
| Research Abstract |
We elucidated the mechanisms of escape from Trastuzumab-mediated ADCC using esophageal squamous cell carcinoma cell clones. Esophageal SCC cell line TE4, which is highly susceptible to Trastuzumab-mediated ADCC, were repeatedly treated with Trastuzumab-mediated ADCC, and the surviving tumor cells are cloned by limited dilution and selected as 68 escaped tumor clones. Furthermore, the degree of permeabilization induced by PFN and apoptosis induced by the combination of PFN with GrB in tumor cell clones was analyzed. As a result, lower sensitivity for PFN/GrB on tumor clones was related to the reduced Trastuzumab-mediated ADCC. In conclusion, lower susceptibility to the perforin-granzyme system is one of the important mechanisms explaining escape from Trastuzumab-mediated ADCC.
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