Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism forradiation brain necrosis development. Bevacizumab alleviates brain edema symptoms caused by radiation brain necrosis through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients’ Karnofsky performance status (KPS) scores and brain necrosis imaging. However, necrosis is irreversible, and hypoxia and ischemia localized in the brain necrosis area may easily lead to radiation brain necrosis recurrence after bevacizumab is discontinued. Further studies are necessary to investigate brain necrosis diagnoses, bevacizumab indications, and the optimal mode of administration, bevacizumab resistance and necrosis with a residual or recurrent tumor.

Peer reviewed article authored by (Zhuang H, Yuan Z, Wang J, Zhao L, Pang Q, Wang P). Read article or submit your manuscript for publishing.

Background: To investigate the effectiveness and mechanism of¹²⁵I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro.Methods: The CL187 cell line was exposed to radiation of⁶⁰Coγ ray at high dose rate of 2 Gy/min and¹²⁵I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under¹²⁵I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI) staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR) and Raf under continuous low dose rate irradiation (CLDR) and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence.Results: The relative biological effect (RBE) for¹²⁵I seeds compared with⁶⁰Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G₂/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%.P< 0.05 vs. control groups by Student's t-test were found in every treated group both in apoptosis and in G₂/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change.Conclusion: ¹²⁵I seeds resulted in more effective inhibition than⁶⁰Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G₂/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could influence the proliferation of cells via MAPK signal transduction.

The optimal administration time for applying epidermal growth factor receptor inhibitors combined with radiotherapy has been unclear. We investigated the efficacy of combining gefitinib with radiation in different treatment schedules. We demonstrated that gefitinib was administered to A549 lung cancer cells in three ways (administration before irradiation, administration upon irradiation, administration after irradiation) to establish the radiosensitizing effect. Cell‐survival rates were evaluated by colony‐forming assays. Cell apoptosis and cell‐cycle distribution were investigated using flow cytometry; meanwhile, the expression of P21, Cdc25c, Bcl‐2, Bax, Rad51 and phosphorylated DNA‐PKcs (phospho‐DNA‐PK) after 6 Gy irradiation and/or gefitinib were determined by Western blot analysis. The sensitizer enhancement ratios of the gefitinib administration before irradiation, administration upon irradiation, and administration after irradiation groups were 2.23, 1.51 and 1.30, respectively. A higher apoptosis rate and G₂/M phase arrest were observed in cells at 48 h after exposure to 6 Gy irradiation when gefitinib was administrated before irradiation. Increased cell apoptosis and cell cycle arrest were further supported by the expression changes of Bcl‐2, Bax, P21, Cdc25c, Rad51 and phospho‐DNA‐PK at the same time. The best radiosensitizing effect was obtained when gefitinib was delivered before irradiation. Apoptosis might be an important way of cell killing and G₂/M phase arrest might be an important mechanism of apoptosis. The expression proportion changes of P21/Cdc25c proteins may play an important role in G₂/M cell cycle arrest. Moreover, the pro‐apoptotic/antiapoptotic and DNA repair factors may be important modulators taking part in the molecular events of the radiosensitizing effect of gefitinib combined with irradiation. (Cancer Sci 2009)

In order to investigate the efficacy of bevacizumab on the treatment of radiation cerebral necrosis, patients who were diagnosed with radiation cerebral necrosis by imaging after stereotactic radiotherapy were collected. Bevacizumab was applied at a dose of 5 mg/kg once every three weeks at least three times. The changes in cerebral necrosis symptoms before and after treatment, the cerebral edema volume, the cerebral necrosis volume, and the changes in magnetic resonance imaging (MRI) strengthening phase signals of cerebral necrosis were used as the first observation point. The side effects of bevacizumab were used as the second observation point. Total of 14 radiation cerebral necrosis patients were treated with bevacizumab between June 2011 and February 2013 were collected. There were 12 symptomatic patients, of whom 10 patients (83.3%) had reduced symptoms. The edema index grades of nine patients (64.29%) improved. The cerebral necrosis volumes of 13 patients (92.86%) decreased. The T1 phase signal strengths of the intracranial enhanced MRIs of 12 patients (85.71%) significantly decreased. The clinical side effects of bevacizumab were mild. In conclusion, Preliminary results showed that treatment of radiation cerebral necrosis using bevacizumab was safe and effective. This treatment measure is worthy of further study.