2006 Fiscal Year Final Research Report Summary
The development of early diagnostic marker for peritoneal metastasis, and the management of tumor fibrosis through angiotensin II type I (AT1) receptor in gastric cancer.
| Project/Area Number |
17591383
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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 |
FUSHIDA Sachio University Hospital, Instructor, 医学部附属病院, 助手 (10301194)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Shinichi Graduate School of Medicine, Instructor, 医学系研究科, 助手 (90272955)
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| Project Period (FY) |
2005 – 2006
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| Keywords | serum type IV collagen / peritoneal metastasis (recurrence) / peritoneal fibrosis / Angiotensin II type 1 receptor / candesartan |
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| Research Abstract |
Evaluation of the serum type IV collagen for early diagnosis of peritoneal metastases (recurrence)
The purpose of this study is to determine whether the type IV collagen, which is marker of hepatic fibrosis, could be useful biomarker for peritoneal metastasis. Type IV collagen was measured in 112 patients who were diagnosed wit gastric cancer : early cancer 55 (Group A), advanced cancer 43 (Group B), patients with peritoneal metastasis 27 (Group C). And they were compared with conventional biomarker (CEA, CA19-9, CAl25). The median type IV collagen levels in Group C was significantly higher than Group A and B (p<0.0001). In the clinical course of 13 patients with peritoneal metastasis, all of the serum type IV collagen levels were increasing according to their tumor progression. Furthermore, 3 of 5 patients, who were in the high risk group for peritoneal recurrence, were found peritoneal recurrence by laparoscopy without clinical, radiological, biochemical symptoms. These findings sugge
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st that the serum type IV collagen is a useful marker for early diagnosis of peritoneal metastasis with gastric cancer.4
Angiotensin II activates MAP kinase and NF-kB through angiotensin II type I receptor in gastric cancer cells
Four of 5 gastric cancer cell lines were found angiotensis II type 1 (AT1) receptor expression using western blot analysis. Angiotensin II stimulated growth of AT1 positive gastric cancer cell and this proliferative response was inhibited by candesartan, a specific AT1 receptor antagonist. Angiotensin II plays a role in the growth of AT1 positive gastric cancer cells through MAP kinase activation by ERK1/2 phosphorylation and surviving induction as antiapoptotic molecule by NF-kB activation.
One of the AT1 receptor expressing cell lines, OCUM2MD3, which had a very high peritoneal metastatic potential, was used as in vivo experiment. OCUM2MD3 made peritoneal metastasis including massive ascites and metastatic nodules 4weeks after intraperitoneal injection of 1×107 cells in nude mice. To elucidate whether over-expression of AT1 correlate to tumor progression, AT1 receptor antagonist, candesartan, has been treated everyday from 1 week after tumor injection. The candesartan group showed a significant longer survival than control group. These finding suggest that AT1 activation correlates tumor progression and its receptor antagonist may be a candidate for the molecule targeting therapy Less
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