Autophagy is an evolutionarily conserved cellular response to conditions of stress such as hypoxia, which induce radioresistance in cancer cells. We studied the mechanism of action of hypoxia on autophagy and radiosensitivity in colon cancer cells. In the human colon cancer cell lines SW480 and SW620, autophagosomes were analyzed to evaluate autophagy by flow cytometry. The expression of hypoxia inducible factor-1α (HIF-1α), Bcl-2, and miR-210 was detected by western blotting and quantitative real-time polymerase chain reaction (PCR). HIF-1α and miR-210 inhibition was induced by siRNA transfections. Apoptosis detection and colony assays were performed to determine radiosensitivity. HIF-1α and miR-210 showed a significant increase under hypoxic condition. The inhibition of HIF-1α decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1α induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. Our results imply that autophagy contributes to the reduction of radiosensitivity in hypoxic environment, and the process is mediated through the HIF-1α/miR-210/Bcl-2 pathway in human colon cancer cells.

To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.

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The objective of this study was to evaluate the necessity of concurrent chemotherapy in T1-2N1 nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT).The retrospective analysis was conducted using the paired comparison method. We matched cases to controls using the greedy matching algorithm with 1:1 control to case ratio. Controls were matched to cases by factors including age, gender, T stage, and duration of RT. The control group included patients received IMRT alone. In another group, concurrent chemotherapy (DDP 40 mg/m2/w) was administrated to each paired patient.From Jan 2009 to Dec 2011, a total of 86 well-balanced T1-2N1 (2002 UICC staging system) NPC patients were retrospectively analyzed. Half of them (43 patients) received radical IMRT alone and another 43 received concurrent chemotherapy with IMRT (CCRT). Median follow-up is 37.4 months (4.8–66.2 months). All patients received a radiation dose of 66Gy/30Fx. In the CCRT group, all patients received a cumulative dose of ≥200 mg/m2. The differences of 3-year overall survival (OS), 3-year progression-free survival (PFS), 3-year relapse-free survival (RFS), and 3-year metastasis-free survival (MFS) between 2 groups were not significant (P > 0.05). The most frequently increased toxicities related to chemotherapy were mild to moderate leukopenia (P = 0.003) and mild anemia (P = 0.008).Omission of weekly cisplatin chemotherapy resulted in comparable survival outcomes to CCRT in IMRT populations. More data from future randomized trials are warranted to further confirm it.