The Clinic And Experiment Research On Related Factor Of Bone Metastasis Of Bresat Cancer

Breast cancer is one of the most common carcinoma of women. These patients mainly die of the metastases. It is difficult to prevent or treat these metastases of breast cancer at present. Advanced breast cancer is frequently associated with destructive osteolytic bone metastases that are accompanied by serious complications, including sever bone pain, pathological fractures, hypercalcemia, neural compression syndrome. There is no any effective method to treat bone metastases regardless of chemotherapy, radiotherapy, isotopic therapy. Since the 90 era, an important discovery is that the proliferation and metastases of tumor is relied on the angiogenesis. The anti-angiogenesis treatment is directly aimed at the endothelia cell or related factors with angiogenesis, can inhibit or destroy neovascularization and block the growth and metastases of cancer. But the anti-angiogenesis treatment is also in laboratory research. So we design the research process in below. On the clinic, we suck 5 ml bone marrow as soon as the patient is anesthetized in operation. We identify the bone micrometastases of breast cancer through nested RT-PCR detecting the CK19 mRNA. We count the MVD of the primary breast cancer using anti-CD34 to target the endothelia cell; detect the VEGF, MMP-2 mRNA with RT-PCR and VEGF, MMP-2 protein with western blot; detect apoptosis using tunnel; detect ER PR and cer-B-2 with immunohistochemistry; detect Bcl-2, Fas and SPF with FCM; and record the tumor size and lymph node metastases from the clinic document. Result: The incidence of bone micrometastases is 54.86%, and there is no relation with lymph node metastases. High MVD is associated Iv with the lymph node metastases and bone micrometastases, is not associated with the size of tumor. Comparing with the breast fibroadenoma, the amount mRNA and protein of VEGF and MMIP-2 of the breast cancer increased markedly. The apoptosis of the primary breast cancer is associated with rising Fas and lowing Bcl-2. At the same moment, the higher apoptosis is, the higher proliferating(SPF) is. One important discovery is the MVD of tumor is the only one indicator for the bone mierometastases using Cox proportional hazards model analysis. On the whole, we think that RT-PCR detecting CK19 mRNA is a reliable method to identify the bone mierometastases of breast cancer and the bone micrometastases is associated with high MVD and VEGF MMP-2. Therefore, anti-angiogenesis may be an effective treatment for the bone metastases of breast cancer. Because there is no any clinic medicine for anti-angiogenesis, we select two peculiar medicine and investigate their anti-neovascularization effect. We investigate the anti-neovascularization of PAA and HCPT using a series of angiogenesis research models: the endothelia cell proliferation, migration model ,a modification of the chick embiyo chorioallantoic membrane(CAM) assay, DAPI apoptosis, FCM detecting Bcl-2.Result: these two medicine can obviously inhibit the proliferation, migration of endothelia cell and cause obviously apoptosis.The apoptosis is result from down-regulation Bcl-2 of the cell. Therefore, the PAA and HCPT is directly affect the endothelia cell and the mechanism of anti-angiogenesis is down-regulation of Bcl-2 of endothelia cell.