Molecular targeting therapy for digestive carcinomas

我们基于肿瘤细胞和实质细胞之间的相互作用，研究了消化道癌的发展、侵袭和转移机制。丝裂原诱导的环加氧酶（cox-2）在大多数肿瘤组织和大多数肿瘤细胞中上调，并增强血管生成因子的表达。COX-2抑制剂抑制这些血管生成因子的产生。另一方面，cox-1在血管内皮细胞中表达，参与肿瘤血管生成。使用小鼠异种移植物的体内研究表明，非甾体抗炎药抑制血管生成，抑制细胞复制，诱导程序性细胞死亡，并阻断肿瘤生长。此外，在敲除cox-2的小鼠中，肿瘤不会生长，这可能是因为cox-2在肿瘤周围基质细胞的血管生成因子产生中也起着重要作用。人体研究和动物研究表明，cox-2在胃肠道中表达上调，以应对多种刺激，包括组织损伤、生长因子、幽门螺杆菌感染和胃泌素。此外，一项研究表明，COX-2上调与胃癌患者的淋巴浸润和淋巴转移有关。这些研究都清楚地表明，cox-2在消化道肿瘤的发生、生长、侵袭和转移中起着关键作用。因此，cox-2是预防和治疗消化道肿瘤的重要分子靶点。

We investigated mechanisms for development, invasion and metastasis of digestive carcinomas, based on interactions between neoplastic cells and parenchymal cells. Mitogen-inducible cyclooxygenase (cox-2) is upregulated in most neoplastic tissues as well as most neoplastic cells, and enhances expression of angiogenic factors. COX-2 inhibitors suppress production of these angiogenic factors. On the other hand, cox-1 expressed in vascular endothelial cells participates in tumor angiogenesis. In vivo studies using mouse xenografts showed that non-steroidal anti-inflammatory drugs suppress angiogenesis, inhibit cell replication, induce programmed cell death, and block tumor growth. Furthermore, tumors do not grow in cox-2 knockout mice, possibly because cox-2 also has important roles in angiogenic factor-production in the perineoplastic stromal cells.Human studies and animal studies demonstrate that cox-2 is upregulated in gastrointestinal tract in response to various stimuli including tissue damage, growth factors, H.pylori infection and gastrin. In addition, a study shows that COX-2 upregulation is associated with lymphatic invasion and lymphatic metastasis in patients with gastric carcinomas.All of the studies clearly indicate that cox-2 plays pivotal roles in development, growth, invasion and metastasis in digestive tumors. Thus, cox-2 is an important molecular target in prevention and treatment in digestive cancers.