[Radioresistant subline of human glioma cell line MGR2R induced by repeated high dose X-ray irradiation].

BACKGROUND & OBJECTIVE: Radiotherapy is one of the most important adjuvant treatments for patients with malignant glioma, but radiosensitivities of gliomas are widely various. This study was to induce human glioma cell line MGR2 to become a stable radioresistant cell subline, and investigate the mechanisms of radioresistance. METHODS: Human glioma cell line MGR2, with survival fraction of 2 Gy (SF(2)) of 0.18+/-0.05, was irradiated by intermittent high dose X-ray (2 Gy for 3 times, 5 Gy for 2 times). After each irradiation, the cells were cultured for 5 to 8 weeks and received irradiation again. The whole process of irradiation and culture lasted for 11 months. The cells derived from MGR2 were obtained and named MGR2R (MGR2 radiation induction). Double times of MGR2 and MGR2R cells were determined by MTT assay. Dose-survival curves, radiobiological parameters and SF2 were determined by colony-forming assay and line-quadratic model. The variation of their cell cycles was investigated by flow cytometry and cell cycle synchronization of serum-starvation. RESULTS: The double time of MGR2 cells was 3.6 days, while that of MGR2R cells was 4.0 days. The growth rate of MGR2R cells was slower than that of MGR2 cells. Using colony-forming assay and line-quadratic model, the parameters of MGR2 and MGR2R were obtained. The alpha values of MGR2 and MGR2R were 0.447 and 0.089 (t=4.524, P=0.011), the beta values were 0.177 and 0.141 (t=1.562, P=0.193), and the SF(2) were 0.208 and 0.478 (t=-6.062, P=0.040), respectively. The radioresistance of MGR2R cells was stronger than that of MGR2 cells. The distribution of cell cycle in MGR2 cells after synchronization were 54.8% in G(1) phase, 30.9% in S phase, and 14.3% in G(2) phase; 24 h after loss of synchronization, the distribution of cell cycle were 35.9% in G(1) phase, 51.2% in S phase, and 12.8% in G(2) phase. The distribution of cell cycle in MGR2R cells after synchronization were 55.7% in G(1) phase, 27.8% in S phase, and 16.6% in G(2) phase; 24 h after loss of synchronization, the distribution of cell cycle were 56.4% in G1 phase, 26.7% in S phase, and 16.9% in G(2) phase. MGR2R cells appeared G(2) phase arrest before synchronization, and G1 phase arrest after loss of synchronization. CONCLUSIONS: After intermittent high dose X-ray irradiation, radiosensitive cell line MGR2 has been induced to be relatively radioresistant (MGR2R). MGR2R cells grow slower and have G(1) phase and G(2) phase arrest which might relate to its radioresistance.

[Individualized therapy and outcomes of microsurgery, radiotherapy, and chemotherapy for astrocytoma].

BACKGROUND & OBJECTIVE: Astrocytomas, constitute about 75% of neuroepithelial tumors, is one of the most common primary tumors in central nervous system with fairly high incidence and poor prognosis. Individualized multimodality is the hope for improving prognosis of patients with astrocytoma. This study was designed to investigate the efficiency of individualized treatment of microsurgery, radiotherapy, and chemotherapy for 62 patients with astrocytoma. METHODS: Sixty-two patients with astrocytoma in study group were treated with individualized multimodality of microsurgery, postoperative radiotherapy, and/or postoperative chemotherapy according to in vitro sensitivity assay. After microsurgery, 59 patients accepted radiotherapy, 46 patients received chemotherapy. Fifty patients with astrocytoma in control group were treated with conventional treatment of surgery, chemotherapy, and radiotherapy. After surgery, 31 patients received radiotherapy following by BCNU chemotherapy, while 19 patients accepted BCNU chemotherapy following radiotherapy. Pathologic diagnosis of patients in study group were 19 cases of grade, 32 cases of grade III, and 11 cases of grade IV; in control group were 13 cases of grade II, 28 cases of grade III, and 9 cases of grade IV. Mean follow-up time were 25.8 months, and the outcome was evaluated by MRI, KPS, and survival rate. RESULTS: Tumor total resection rate in study group was 67.7%, while that in control group was 58.0%. There was no significant difference of KPS and survival rate in patients with low-grade astrocytoma between 2 groups, while the outcome of patients with malignant astrocytoma was significantly improved by individualized treatment. In study group, 2-year expectant survival rate of patients with astrocytoma of grade III, and grade IV were 93.7%, and 36.3%, while in control group were 67.5%, and 22.2% (P< 0.05). In glioblastoma patients, median survival time of study group was 18.68 months, while that of control group was 12.83 months (P< 0.01). CONCLUSION: Individualized microsurgery may improve the total resection of astrocytoma, and benefit to postoperative treatment.Individualized radiotherapy/chemotherapy may prevent patients from some complications. Individualized management may improve prognosis of patients with astrocytoma, particularly malignant astrocytoma.