Colorectal Cancer Is The Formation Of The Significance Of The Process Of Tumor Angiogenesis And Apoptosis And Vegf And P53 Expression

The growth and maintenance of solid tumors is angiogenesis dependent, in-cluding colorectal cancer. The ingrowth of new blood vessels provides nutrients and a means of eliminating metabolic waste products by a process other than sim-ple diffusion. The pioneer of angiogenesis research, Judah Folkman, has stated that "once tumor take has occurred, every increase in tumor cell population must be preceded by an increase in new capillaries converging on the tumor". Tumor in an avascular environment has slow linear growth, the size is limited in < 2mm. After vascularization it becomes exponential. Tumors angiogenesis not on-ly provides nutrients but also provides the easy way to metastasis. Therefore an-giogenesis play a important role in tumor growth and metastasis.Tumor growth is related to a critical balance between tumor cell prolifera-tion and apoptosis that is regulated by angiogenesis. Folkman et al proposed a hypothesis for tumor dormancy that may apply to variety of tumors in which blocked angiogenesis results in balanced tumor cell proliferation and apoptosis. Experimental studies revealed that tumor cells in a prevascular state may repli-cate as rapidly as those in an expending vascularized tumor, but the generation of new cells is balanced by dying tumor cells ( e. g. apoptosis of individual cells). In a study of transforming growth factor ?β1 ( TGF - β1) which induces angiogenesis and capillary morphogenesis, it has been found that capillary mor-phogenesis in vitro is associated with apoptosis. The inhibition of angiogenesis limits tumor growth by elevating the incidence of apoptosis. Holmgren et al dem-onstrated that apoptosis in micrometastases is significantly reduced after induc-tion of angiogenesis, although the high proliferation rate remains unchanged. If angiogenesis is suppressed, the metastasis remains dormant and exhibits a high incidence of apoptosis. When angiogenesis is induced, apoptosis is concomitant-ly reduced and the metastases grow in size.It is believed that the balance of angiogenesis inducers and inhibitors gov-erns the angiogenesis switch. The key finding in this field was the discovery of vascular endothelial growth factor ( VEGF) , which is a highly potent angiogenic molecule specific for endothelial cells. Previous studies indicated that VEGF plays an important role in tumor angiogenesis in clinical human tumors, and that VEGF is a predictive factor for prognosis in colorectal cancer patients in associa-tion with metastatic potential. Some investigations demonstrated the antiapoptotic function of VEGF by induction of Bel - 2 expression, activation of the mitogen -activated protein kinase ( MAPK) , and inhibition of c - jun - NH3 - kinase ( JNK). With regard to p53 , there have been several studies indicating its regu-latory role in VEGF induction. Kieser et al showed that mutant p53 stimulated VEGF expression by activating protein kinase C. It also was reported that wild -type p53 represses v - Src mediated VEGF up - regulation. Wild - type p53 can also regulate the normal cell to produce high level antiangiogenic factor -Thrombospondin(TSP). Although experimental evidence suggests that p53 mod-ulates angiogenesis, most studies into human cancer have been unable to confirm a correlation between p53 gene status and MVD. It need to be study more.Colorectal is a major cause of cancer death in many countries and, in most cases, is believed to have developed from adenoma. As tumors of various stages from dysplasia to malignancy are available, the well - established adenoma -carcinoma sequence of colorectal carcinogenesis provides an ideal model for the study of the deregulated cell proliferation and apoptosis in human cancers. Using this model, disturbed cell proliferation and apoptosis during colorectal carcino-genesis have been demonstrated. However controversy exists with regard to the alteration of apoptosis in the adenoma - carcinoma sequence, and little is known about how such alterations occur. On the other hand, a crucial role for angio-genesis i...