Erlotinib is a novel therapeutic agent for cancer treatment. This study was performed to investigate the role of c-MET-PI3K-AKT pathway in the regulation of erlotinib-induced radiosensitization.A973 lung adenocarcinoma cells treated with 6 Gy of radiation were incubated in the presence of erlotinib. The apoptotic rate after 24 hours, the colony-formating rate after 14 days, and changes in the c-MET expression levels after 14 days of irradiation were examined. Surviving fractions in different treatment groups (blank control, radiation alone, erlotinib alone, anti-c-MET monoclonal antibody alone, combined erlotinib and radiation, and combined erlotinib and radiation with anti-c-MET monoclonal antibody groups) were determined, the survival curves were plotted, and the sensitizer enhancement ratio was calculated using colony formation assays. Expressions of c-MET, p-c-MET, PI3K, AKT, and p-AKT in cells in different treatment groups were examined by Western blot analysis.The apoptotic rate in the combined erlotinib and radiation group was higher than those in single treatment groups; however, the colony-forming rate remained approximately 2.04 ± 1.02%. The expression of c-MET in colony-forming cells in the combined group significantly increased, and the blockade of c-MET activity significantly enhanced the radiosensitizing effect of erlotinib. The expression of c-Met, p-c-MET, PI3K, AKT, and p-AKT among colony-forming cells significantly decreased upon the inhibition of c-MET.Upregulated activity of the c-MET-PI3K-AKT pathway was found to be important for cell survival under combined the treatment with erlotinib and radiation. The blockade of the c-MET-PI3K-AKT signaling pathway enhanced the radiosensitizing effect of erlotinib.
Stereotactic ablative radiotherapy (SABR/SBRT) is a revolutionary technique for tumor therapy. Its advantages are especially beneficial for the treatment spinal tumors. It has a wide range of indications in radiotherapy alone and in preoperative and postoperative treatments for spinal tumor. The mechanism of stereotactic radiotherapy for spinal tumors is special, and completely different from traditional radiotherapy. Compared with traditional radiotherapy, SBRT creates more DNA double-strand breaks, leads to less DNA damage repair, and also has anti-vascular effects, in situ vaccine effects and abscopal effect. In the present study, the literature regarding SABR for the treatment of spinal tumors is summarized, and we reviewed characteristics of SABR and spinal tumors, as well as the clinical efficacy and toxicity of SABR in treating spinal tumors. In addition, we proposed several issues around the SABR treatment of spinal tumor, the standard of treatment dose, and the post-treatment follow-up. We also made predictions with respect to future management of spinal tumors, SABR development, multi-modality integration between SABR and other treatments, and other future development trends, thereby providing future research directions as a contribution to the field.
Objective: To investigate the treatment efficacy of ultra-low-dose bevacizumab for cerebral radiation necrosis. Methods: Patients with cerebral radiation necrosis after stereotactic radiotherapy (SRT) confirmed by imaging were included. Bevacizumab (1 mg/kg, once every three weeks, for at least three continuous treatments) was administered. The primary endpoints included change in cerebral necrosis symptoms, volume of intracranial edema, and changes in MRI signals. The secondary endpoints were adverse reactions of bevacizumab treatment. Results: In total, 21 patients were included in this study, all of whom received SRT between December 2016 and February 2019, developed cerebral radiation necrosis, and were treated with bevacizumab. Twenty patients were symptomatic from radiation necrosis, and the symptoms were alleviated in 18 patients (90%). Twenty patients had intracranial edema, and the grade of edema index (EI) was improved in 19 patients (95%). The intensity of the intracranial-enhanced MRI signals was significantly reduced in 20 patients (95.24%). The adverse reactions of bevacizumab treatment were mild, and no adverse reactions more severe than grade 2 were found. Conclusion: The preliminary results showed that ultra-low-dose bevacizumab had high efficacy for treating cerebral radiation necrosis, and could be a valid alternative to the standard-dose bevacizumab. Clinical registry: Chinese clinical trial registry (ChiCTR-IOD-16009803). Keywords: bevacizumab, cerebral radiation necrosis, stereotactic radiotherapy, drug dose, edema index
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