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Experimental Study On The Effect Of Anticancer Drugs On Angiogenesis Of Colorectal Carcinoma

Posted on:2003-09-19Degree:MasterType:Thesis
Country:ChinaCandidate:B KongFull Text:PDF
GTID:2144360065450178Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: The growth of solid tumors depend on a process called angiogenesis, whereby the ingrowth of new blood vessels provide oxygen, nutrients and a means of eliminating metabolic waste products other than simple diffusion. The generation and development of tumor can be divided into two periods: (1) prevascular state: tumor cells are dormant; (2) vascular state: tumor cells divide and grow. Therefore, angiogenesis is the master key of tumor growth..Angiogenesis of tumor is a complicated multistep process. The exact mechanism whereby angiogenesis occurs is not completely known so far. Generally speaking, it involves proliferation, migration, differentiation of the endothelial cells and formation of a lumen finally.In the period of prevascular state, angiogenic switch happened mainly. Before this period, tumor cells are dormant. Once the microenviroment change, such as hypoxia, nutrition deficiency, acidified PH, NO increasing or p53, H-ras, VHL gene mutation and so on, umor cells proliferate which make local hypoxia. At this time, newblood vessels are needed, Then tumor cells transform to angiogenic phenotype.With the growth of tumor, it get into the period of vascular state. Some tumor cells turn into angiogenic phenotypic cells and secrete angiogenic growth factors. Endothelial cells are activated to proliferate and migrate. The proliferation and migration of endothelial cells are toward the angiogenic stimulus. Cell cords interfuse futher to formation of functioning vessel lumen. Adding to the leaky basement membrane, this is the whole process of angiogenesis.Moreover, in the period of prevascular state, metastasis scarcely happened. Angiogenesis is the first step of neoplastic infiltration and metastasis. Newly formed vessels are lack of smooth muscle and have only one layer of endotheliai cells and leaky or weak bassment membranes with tumor cells can penetrate more easily than those of mature vessels. Enormous studies suggested that an enhanced microvessel density(MVD) reflects an increased biologic malignant potential of carcinomas.The growth of a tumor and its ability to metastasize is angiogenesis-dependent.This proffers important theoretical foundation for clinical practice. The most impornant about it, also the focus people study is inhibit the growth and metastasis of tumor through inhibit angiogenesis. Angiogenesis has been proposed as a possible target foranticancer treatment earliest in 1970' The inhibition can take place by one of three methods: (l)by inhibiting the growth factors or cytokines that initiate the entire process of angiogenesis, (2)by neutralizing the growth factors or of angiogenesis, (2)by neutralizing the growth factors or cytokines released, (3)by inhibiting endothelial cell DNA synthsis and proliferation.About tumor therapy, Denekamp has stated that united using of angiogenesis inhibitor and direct cytotoxic drugs is the ultimate selection scheme of the therapy of malignant carcinomas, but the mechanisms of them should be studied separately.Through the 30 years ' development of tumor angiogenesis-targeted therapy, it has made giant strides in the late 10 years. More recently, the focus on antiangiogenic therapy has led to the rational search for agents with selective effects on endothelial cell proliferation with the assumption that a high proliferation rate of endothelial cells within tumor tissue will permit improved selectivity against tumor versus normal tissues. This " angiosuppresive" effect make people to study chemotherapeutic agents such as paclitaxel, bleomycin, mitoxantrone and suggest that a hidden "antivascular" effect may be operating in a number of conventional anticancer therapies.On the other hand, the generation and development oftumor are related with angiogenesis, whereas angiogenesis is related with apoptosis. Ample evidence indicates that angiogenesis within a variety of tumors (breast, gastric, liver, prostate, head and neck carcinomas) correlates with spontaneous apoptosis of tumor cells. There is the simil...
Keywords/Search Tags:Anti-Cancer drugs, Colorectal carcinoma Angiogenesis, Topotecan, MVC
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