Mechanisms of escape from trastuzumab-mediated ADCC in esophageal squamous cell carcinoma.
Project/Area Number |
20790947
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Digestive surgery
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Research Institution | University of Yamanashi |
Principal Investigator |
KAWAGUCHI Yoshihiko University of Yamanashi, 医学部附属病院, 診療助教 (80402048)
|
Project Period (FY) |
2008 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 食道扁平上皮癌 / 抗体療法 / trastuzumab / Herceptin / 抗体依存性細胞傷害 / Trastuzumab / 抗体依存性細胞障害 |
Research Abstract |
We elucidated the mechanisms of escape from trastuzumab-mediated ADCC using esophageal squamous cell carcinoma cell clones. The ADCC assay with purified NK cells showed significantly susceptibility to trastuzumab-mediated ADCC in tumor cell clones. These results indicated that the sensitivity to trastuzumab-mediated ADCC was mainly due to the difference in susceptibility to NK cell-mediated ADCC. 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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Report
(3 results)
Research Products
(15 results)