Angiostatin On The Cural Effect Of H22 Liver Cancer In Mice And The Immune Influence Of T Cell

Angiostatin (AS) can specifically inhibit the proliferation and migration of vascular endothelial cell,preventing new blood vessels of tumor. It has become a research focus on solid tumor therapy. Currently,due to limited sources of natural AS,not high transfection efficiency,easy to mutation and hard to break and so on for gene therapy of AS,the combination of AS and traditional treatment have become its development orientation. In recent years,my departments have performed the combined research the internal radiation of radionuclides and AS for tumor,it was found the apparent joint action. It has laid experimental foundation for the "double target" treatment of solid tumors.Tumor development and immune function are closely related. when the host immune dysfunction or inhibited,the incidence of tumors would be increased; however, In progressive stage of tumor growth,the patient's immune function is further suppressed,The two factors are mutually affected and restricted. In the anti-tumor immune responses, cellular immunity plays an important role. Although all lymphocytes are likely to participate in the action,a large number of studies have shown that T cells plays the most prominent role,especially in CD8 cytotoxic T cells (CTL) and CD4 T cells (TH), the former can recognize the tumor cell surface antigen by MHC I molecules,leading to tumor cell lysis; which allows the proliferation of CTL precursor cells, resulting in a large number of effector cells. Therefore, CD8 T cell and CD4 T cell numbers and function were detected that was able to evaluate treated efficacy and diseases prognosis in anti-tumor immunotherapy.Previous studies showed that the tumor cells produce large amounts of immunosuppressive factors,making CD8 T cells increase,CD4 T cells and NK cells decrease significantly,ratio of CD4/CD8 decrease,thus resulting in impaired immune function. It creates the conditions for the rapid growth of tumor, invasion , metastasis and secondary infection. Therefore,comprehensive and effective treatment of cancer should focus on improving CD4,NK cells quantity and function of other anti-tumor cells,making further that the ratio of CD4/CD8 cells back to normal.Low-dose X-ray and ionizing radiation can stimulate the immune system through a number of related cells and changes in cellular and molecular activity, prompting the immune response which has become a consensus. Early in the 1970s,it had reported that low doses of irradiation could increase blood lymphocytes 3H-TdR incorporation . It could be expressed as lymphocytes and its subsets division,accelerated proliferation,and the increased formation of antibody levels, enhanced activity of NK cells,promoted secretion of cytokines,etc. However,the report on the exposure to radionuclides on the role of the immune system,especially for cancer patient's immune function is very few. There were studies which were focused on synthesis, distribution and anti-angiogenesis mechanism of angiostatin in vivo last year,but the role of angiostatin in the immune system have not been reported. This study contains four steps. the first step is isolated plasminogen from human plasma fibrinolytic,in the L-lysine Sephamse 4B affinity chromatography and digested within the limited access to elastase fragments of angiostatin,using Iodogen method of radioactive iodide radionuclide marker to obtain a relatively high labeling yield (131)^I-AS,cultured rat derived H₂₂ hepatoma cells,select C57 strain mice to establish tumor models,divided into four groups and in turn injected with AS,(131)^I,(131)^I-AS and saline. After 14 days,flow cytometry was performed by peripheral blood of the mice,the data of CD4 T,CD8 T lymphocytes were obtained. Finally,statistical analysis was used to obtain the cellular immunity by (131)^I,AS or the combination of (131)^I and AS.Results:1. Relatively pure angiostatin was obtained from human plasma using elastase limited hydrolysis,the molecular weight was 38KD by gel electrophoresis.2. AS tag was performed by Iodogen iodination method,which was simple,high labeling rate,good stability in vitro,obtained (131)^I-AS reached the experiments standard.3. The combination of 131 I and angiostatin had obvious anti-tumor synergistic effect .4. Both 131 I and angiostatin can affect the number of anti-tumor immune CD4 and CD8 T cells,low-dose 131 I can stimulate the immune system,increase CD4 T cells quantity and CD4/CD8 relative value,and decrease CD8 T cells quantity. The differences possess statistical significance.