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.

血清IV型胶原在腹膜转移(复发)早期诊断中的价值本研究的目的是探讨作为肝纤维化标志物的IV型胶原能否作为腹膜转移的生物标志物。对112例确诊为胃癌的患者进行了IV型胶原测定，其中早期癌55例(A组)，晚期癌43例(B组)，腹膜转移27例(C组)。并与常规生物标志物(CEA、CA19-9、CAl25)进行比较。C组IV型胶原中位数显著高于A组和B组(p&lt；0.0001)。在13例腹膜转移患者的临床病程中，血清IV型胶原水平均随肿瘤进展而升高。腹膜复发高危组5例中有3例腹膜复发，无临床、放射学、生化等症状。这些发现建议…4血管紧张素II通过血管紧张素II I型受体激活MAPK和核因子-kB在5株胃癌细胞株中有4株表达血管紧张素Ⅱ1型受体。血管紧张素II促进AT1阳性胃癌细胞的生长，这种增殖反应可被AT1受体特异性拮抗剂坎地沙坦抑制。血管紧张素II通过ERK1/2磷酸化激活MAPK和核因子-kB激活作为抗凋亡分子而参与AT1阳性胃癌细胞的生长。OCUM2MD3裸鼠腹腔注射1×107细胞4周后发生腹膜转移，包括大量腹水和转移结节。为了阐明AT1的过度表达是否与肿瘤进展有关，AT1受体拮抗剂坎地沙坦从肿瘤注射后1周开始每天接受治疗。坎地沙坦组的存活时间明显长于对照组。这些发现提示AT1的激活与肿瘤的进展相关，其受体拮抗剂可能是分子靶向治疗的候选药物。

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 … More st that the serum type IV collagen is a useful marker for early diagnosis of peritoneal metastasis with gastric cancer.4Angiotensin II activates MAP kinase and NF-kB through angiotensin II type I receptor in gastric cancer cellsFour 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