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.

评价血清IV型胶原对腹膜转移（复发）的早期诊断本研究的目的是确定作为肝纤维化标志物的IV型胶原是否可以作为腹膜转移的有用生物标志物。对112例胃癌患者进行了IV型胶原测定，其中早期胃癌55例（A组），进展期胃癌43例（B组），腹膜转移癌27例（C组）。并与常规生物标志物CEA、CA 19 -9、CA 125进行比较。C组中IV型胶原水平的中位数显著高于A组和B组（p<0.0001）。在13例腹膜转移患者的临床过程中，所有的血清IV型胶原水平根据其肿瘤进展而增加。腹腔复发高危组5例中，3例腹腔镜检查发现腹腔复发，无临床、影像学、生化症状。这些发现表明， 关于我们 提示血清IV型胶原可作为胃癌腹膜转移的早期诊断指标。4血管紧张素II通过血管紧张素II I型受体激活胃癌细胞MAP激酶和NF-kB蛋白免疫印迹法检测5株胃癌细胞株中有4株表达血管紧张素II I型（AT 1）受体。血管紧张素Ⅱ刺激AT 1阳性胃癌细胞的生长，这种增殖反应被一种特异性的AT 1受体拮抗剂坎地沙坦抑制。血管紧张素Ⅱ（Angiotensin Ⅱ，Ang Ⅱ）通过ERK 1/2磷酸化激活MAP激酶和NF-κ B活化诱导细胞凋亡而参与AT 1阳性胃癌细胞的生长。裸鼠腹腔注射1×107细胞后4周，OEGF 2 MD 3腹腔转移，出现大量腹水和转移结节。为了阐明AT 1的过度表达是否与肿瘤进展相关，从肿瘤注射后1周开始每天治疗AT 1受体拮抗剂坎地沙坦。坎地沙坦组生存期明显长于对照组。这些发现表明，AT 1激活与肿瘤进展相关，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