| Colorectal cancer has been the third most seen malignant tumor in our country, whose mobility is tend to become higher than it was before by years. The prognosis of patients suffered from colorectal cancer is much better than gastric cancer, lung cancer and liver cancer. The main factor related with the therapeutic effects is the stage of patient and the 5-year survival rate is more than 90% for Dukes A but only 30% for Dukes C with the main death reason being regional lymphoid node or remote metastasis especially to the liver. Because the most colorectal cancer cells are insensitive to the chemotherapy or radiotherapy, there is lack of an ideal method for the treatment of unresectable and metastasized tumor.It is an important characteristic for solid tumor to satisfy its abundant blood supply in the course of tumor development by angiogenesis and angiogenesis is indispensable for the tumor's growth and metastasis. Antiangiogenesis has become the new strategy for tumor therapy. In the found antiangiogenesis factors, endostatin is the most potent one and there are no report for toxicity and side effects either in animal experiments or in the latest finished Phase I clinical test. Endostatin can effectively inhibit the migration and vessel formation of the endothelia induced by the vascular endothelial growth factor(VEGF) and inhibit the growth and metastasis of solid tumor in animal experiments. Endostatin can be administrated for long time without the fear of immunogenesis and drug resistance There were data showing that the expression of vascular endothelial growth factor(VEGF) and microvessel density(MVD) in colonic cancer tissue are closing related with the biological behavior of colonic cancer, such as recurrence and metastasis. Endostatin can effectively inhibit the growth of colonic cancer and prevent the liver metastasis.The huge amount of therapeutic dosage(20mg/kg/day), when directly administrated with pure protein, is far beyond the achievement of traditional bioengineering method, and its bioactivity is difficult to maintain, all of which hampered its direct clinical application. The problem is possible to be solved by the method of gene therapy. There had been several successful reports on the replication-deficient adenovirus vectormediated endostatin gene therapy which led to continuous high concentration of expressed endostatin. However for the safety consideration, the large part of El gene region were deleted in the early reformation for replication-deficient adenovirus vector and at the same time this also restricted its replication in tumor cells and the efficient expression of therapeutic gene. Because endostatin inhibits the proliferation of endothelial cells in vitro and the growth and metastasis of tumor in vivo in a dose-dependent manner, a highly efficient gene vector delivery system is destined to be useful for the endostatin to fully exert its antiangiogenetic effects in tumor therapy. At the same time the target and safety of vector, that is how to make the therapeutic gene expressed in the tumor cells but spare the normal cells, are also needed to be concerned in tumor gene therapy.The emergence of tumor-selective replication-competent virus has provided a new way for the tumor gene therapy. In recent years, with the continuous development of virology and oncology great progress has been mad in the field of research work on the tumor-selective replication-competent adenovirus with the El a gene reserved, which makes up some disadvantages of replication-deficient adenovirus vector in tumor gene therapy. The oncolytic virus can selectively replicate in tumor cells and lead to the lysis of the cells, thus to form high concentration of virus in the primary and metastasized tumor tissue. If the virus armed with anti-cancer gene, the gene can be efficiently expressed in the tumor tissue with the viruses' replication. The combined therapeutic effects of both gene and virus will improve the results of tumor therapy.ONYX-015, developed by ONYX pharmaceutical company of USA, i...
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