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Studies On The Treatment Of Gliomas By BNCT And γ Ray Irradiation In Vitro

Posted on:2005-01-26Degree:MasterType:Thesis
Country:ChinaCandidate:R F CaoFull Text:PDF
GTID:2144360122495931Subject:Surgery
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Primary brain tumors are relatively common, with an annual incidence of about 10 per 100 000 of the population. Fifty percent of the malignancies are anaplastic astrocytomas and glioblastoma multiforme. Patients with these tumors usually die within a year of diagnosis despite aggressive surgery followed by conventional radiotherapy and/or chemotherapy. Boron neutron capture therapy (BNCT) is an emerging therapeutic modality for high-grade malignant brain tumors. It is based on the nuclear capture and fission reactions that occur when boron-10, a non-radioactive isotope and a constituent of natural elemental boron, is irradiated with low energy (<0.025 eV) thermal neutrons (nth) to produce high energy (2.3 MeV) a particles and recoiling lithium-7 nuclei. For BNCT to be successful, there must be high levels of 10B in the tumor and low levels in normal brain, and a sufficient fluence of thermal neutrons must be delivered to the tumor. To date, two low-molecular weight boron compounds have been identified to have some of the requisite properties for BNCT of brain tumors, sodium undecahydro-mercapto-closo-dodecacarborate (Na2B12H11 SH) (BSH) and p-dihydroxyborylphenylalanine (boronophenylalanineXBPA). However, the mechanisms of uptake of these compounds are unclear. In the present study we investigated the dependence of incubation time, growth-phase and cell cycle in boron uptake by glioma cells, evaluated the efficiency of BNCT in treating C6 glioma cells in vitro and discussed possible underlying mechanism.Radiotherapy was used to treat brain tumors over 80 years ago. The radio-biological study on gliomas will undoubtedly contribute to the realization of newtherapeutic strategy and minimization of complications. For this reason, we established an apoptotic model of C6 and SHG-44 cells induced by a single dose of y ray irradiation, investigated the dose and time dependence of the killing effect, illuminated the post-irradiation change in cell cycle distribution and discussed the possible mechanism preliminarily.Based on the two parts mentioned above, this research was divided into four sections: 1. studies on BPA uptake in Glioma cells; 2. effects of BNCT on C6 glioma cells in vitro; 3. effects of Co60-r irradiation on glioma cells in vitro; 4. studies on the mechanism of growth arrest in C6 cells induced by y ray irradiation. 1. Studies on BPA uptake in Glioma cellsAbstract: Objective The aim of this section was to investigate the dependence of incubation time, growth-phase and cell cycle in boron uptake by glioma cells. Methods The growing curves of three glioma cell lines and rat astrocytes were made and doubling times were decided from the curve. The cells were incubated in boron medium (10B 50ug/ml) for 4h, 8h, 12h, 16 h, 20 h and 24 h respectively and boron concentrations in these cells were measured by induced couple plasma atomic emission spectroscopy (ICP-AES) thereafter. C6 cells in logarithmic growth-phase (L-phase) and plateau growth-phase (P-phase) were separately incubated in boron medium (10B 50ug/ml) for 8h, 16h and 24h before boron concentration was measured by ICP-AES. After incubation in boron medium for 24h, cells were sorted to G0/G1 phase and G2/M phase by flow cytometry and boron concentration in each fraction was obtained by ICP-AES. Results The boron concentration in glioma cells was always significantly higher than that in astrocytes during the experiment (P<0.01). The concentration of C6 cells in L-phase was significantly higher than that in P-phase (P<0.01). For all three glioma cell lines the boron concentration was significantly higher in G2 /M phase than that in G0/G1 phase (P<0.05). But such difference is not significant for the astrocytes. The boron concentration ratios ofgliomas to astrocytes were 1.46, 1.51 and 1.40 in G0/G1 phase and 3.65, 3.96 and3.76 in G2/M phase for C6, SHG-44 and BT-325 cells, respectively. Conclusion Our results indicate that the BPA uptake is more intensified in glioma cells than in astrocytes. This process can be enhanced in mitosis. The speci...
Keywords/Search Tags:Boron neutron capture therapy, Glioma, BPA, Cell cycle, Apoptosis, γ ray
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