Experimental Studies Of Proliferation Apoptosis And Gene Therapy With Telomerase Anti-sense Oligonucleotides Of Glioma

Tumor is a kind of disease of multiple factors and multiple genes. The common characteristic of all tumors is that the cell cycle is destroyed and cells growth out of control, tumor forms when malignant cells are over proliferation. But from apoptosis point of view, tumor formation is the result of inhibition of cell apoptosis and losing capability of clearing malignant cells. The unbalance station of proliferation and apoptosis is significantly correlated with malignant degree of the tumor, while the malignant degree will affect the curative effect and prognosis directly. In Our study, we observed the proliferation and apoptosis of the glioma with different malignant degree, established the proliferation and apoptosis index, and explored its relation with malignant degree. The expression rate of the telomerase is about 85% in all kinds of human tumor, telomerase is the most widespread and peculiar tumor marker until now. Patients with glioma have short lifespan and high mortality, It is very difficult to cure them. The expression of telomerase indicates that cells become malignant and will proliferate without control. The activity of telomerase is in relationship with malignant degree and prognosis of the glioma. In Our study, we inhibited the activity of telomerase by "anti sense-gene-seal" in order to know about its role in controlling glioma cells. Chemical therapy is one of the essential methods to cure glioma, and drug-resistance is the main reason for the failure of chemical therapy, the most outstanding of drug-resistance is MDR (multidrug resistance) . The obvious characteristic of tumor cells with MDR is the over expression of P170 which is located in the cell membrane, P170 is a kind of drug bump dependent of emergency, it bumps chemical drugs out of the cells, thus decreases the density of drugs in the cells and causes the drug-resistance. The expression of P170 is correlated with the drug-resistance; So P170 protein is a more accurate parameter to examine MDR. Inhibition of MDR increases the sensitivity of tumor cells to chemical therapy, and can acquire better results with low dose of drugs. Part 1. Experimental study on proliferaion, apoptosis of the gliomas and estalishment of the proliferaion/apoptosis index Object: To observe the station of proliferation and apoptosis of the glioma with different malignant degree, establish the proliferation and apoptosis index, and explore its relationship to the malignant degree. Methods: 8 nonnal brain tissues from operation, 69 paraffin-embedded specimens and 26 fresh specimens of the glioma were studied. HE and immunohistochemical staining of PCNA and TUNEL were used to detect the proliferation and apoptosis of the glioma, part of the specimens were marked with fluoresce and detected by FLM. Degree number was decided by positive rate, prolifertive/apoptosis index was the ratio PCNA positive rate to TIJNEL positive rate, and its range was between 0.2?.0. Results: I. PCNA and TUNEL were positive in most of the normal brain and the glioma specimens. The positive rate of PCNA increased accompanied by the malignant degree, while TLJNEL positive rate was not significantly different in gliomas with different malignant degree. 2. The positive rate of PCNA increased as pathology degree becoming high., there was significant difference of PCNA positive rate between normal group, L II grades and ffi. IV grades . TIJNEL positive rate decreased following increasing of malignant degree, there was significant difference between normal group and other groups, IV grade and ot...