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The Experimental Study On Hyperthermia Combined With Radiotherapy On Brain Glioma

Posted on:2003-09-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:J Y ZhouFull Text:PDF
GTID:1104360065460484Subject:Radiation Medicine
Abstract/Summary:PDF Full Text Request
Radiotherapy is considered the most effective therapy following surgery for brain glioma. Because of the radioresistance of glioma cells and the adjacent normal brain tissue is easily injured by radiation, the effect of radiation on brain glioma is failed and most recur locally. So it is necessary to find a new modality therapy or new multimodality therapy.Hyperthermia is the fifth method following surgery, radiotherapy, chemotherapy, immunotherapy to treat tumors, and it's effectiveness has been proven on chest and abdominal tumors. Available reports, however, have not systematically studied the effects of hyperthermia on human glioma cells. The reports of radiofrequency(RF) hyperthermia to treat glioma is rare. For this purpose, we chose this thesis. The main content of this thesis is as follows:1 .The sensitivity of hyperthermia and radiation of human glioma cells SHG-44: The effects were measured by clone forming assay and 3H-TdR and 14C-UR incorporation to study hyperthermia radiosensitization in human glioma cells SHG-44 at different temperature for different thermic time. The optimal condition of hyperthermiacombined with radiotherapy was investigated. The results of this paper showed that if hyperthermia was used alone, there was no clone forming difference taken place when the heating degree was under 42℃, even the heating time was increased. When the temperature of heat was up 42℃, the clone forming ratio was decreased along with the heating time prolonged and the ratio decreased significantly if the heating time was over 40 minutes. When hyperthermia combined with radiotherapy , even mild hyperthermia could depress the clone forming ratio compared to radiotherapy alone and the 3H-TdR and 14C-UR incorporation depressed at most when the interval of radiotherapy and hyperthermia within half an hour. The results indicated that the effect of hyperthermia depended on heating time and heating degree two factors, the threshold for thermal damage was 42℃.The therapeutic effect of heating time over 40 minutes was better. Hyperthermia could boost the effectiveness of radiation against glioma cells significantly even mild hyperthermia, such as 40 ℃ heating degree. At 40 "C or 42 ℃ thermal enhancement ratio for 40 minutes was 1.24 or 1.95 respectively. Maximum effect of thermal enhanced radiosensitization occurred when the cells were heated at 42 ℃ for 40 minutes just before or after irradiation.2.The tumor cells apoptosis is one of important values to evaluate treatment effect. So the apoptosis of SHG-44 human glioma cells induced by irradiation and irradiation combined with hyperthermia were studiedby morphological, FCM and biochemical methods. The relationship between apoptosis and Fas/FasL, Caspase 3 was studied too by RT--PCR. During 12h after radiotherapy or radiotherapy plus hyperthermia characteristic apoptosis cells appeared under electron microcope and typical ladders of DNA were seen by agarose gel electrophoresis in the two treatment groups. In the group that treated by radiotherapy alone, the apoptosis ratio was 29.3%, while the group that treated by radiotherapy plus hyperthermia, the apoptosis ratio was increased to 59.1%. The difference was significantly. The expression of Fas could be found in the two treatment groups and control group, but the expressions of FasL and caspase3 were only in the two treatment groups. The results suggested that the apoptosis was the main way of killing tumor cells by heat enhanced radiosensitivity. There was some relationship between apoptosis and Fas/FasL, caspase3.3.At the bases of experiment of vitro, the vivo experiment was studied too. The models of rats bearing tumors in the brain or (and) hypoderm of right legs were established. They were practical and reliable. RF was used as a source of heating brain tumors. The difference of temperature of brain tumor and adjacent normal brain tissues was observed. When whole brain was heated by RF the temperature in rumor was significantly higher than that in normal brain tissue about 5 deg...
Keywords/Search Tags:Hyperthermia, Radiotherapy, Glioma, Radiofrequency Apoptosis, Fas/FasL, Caspase 3
PDF Full Text Request
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