| Project/Area Number |
20591565
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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 | Kanazawa University |
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Principal Investigator |
YASUMOTO Kazuo Kanazawa University, 附属病院, 講師 (90262592)
|
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| Co-Investigator(Renkei-kenkyūsha) |
YANO Seiji 金沢大学, がん研究所, 教授 (30294672)
MINAMOTO Toshinari 金沢大学, がん研究所, 教授 (50239323)
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 胃十二指腸外科学 / 胃癌 / 腹膜播種(癌性腹膜炎) / CXCR4/CXCL12 axis / Amphiregulin / HB-EGF / EGFR ligands / 癌微小環境 / HER4 / 癌性腹膜炎 / CXCR4 / CXCL12 axis / 分子標的治療 / EGF / EGFR |
|---|
| Research Abstract |
In this study, we showed that the EGFR ligands, amphiregulin and HB-EGF, are abundant in malignant ascites. Amphiregulin strongly enhanced the proliferation of CXCR4-expressing human gastric cancer NUGC4 cells, whereas HB-EGF markedly induced migration of fibroblasts. Moreover, HB-EGF and CXCL12 together enhanced TNF□-converting enzyme (TACE)-dependent amphiregulin shedding from functional CXCR4-expressing NUGC4 cells. Cetuximab, an anti-EGFR monoclonal antibody, effectively reduced tumor growth and ascites formation, and therefore dramatically prolonged survival in nude mice inoculated with NUGC4 cells. Our findings provide a novel insight into treatments that target tumor cells and their microenvironments during the development of peritoneal carcinomatosis from gastric cancer (Clin Cancer Res 2011 in press).
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