Abstract. Tumorigenesis has been considered to be as a result of abnormal cell-cell communication. It has been proposed that exosomes act as communicators between tumors and their microenvironment and have been demonstrated to be involved in tumorigenesis and subsequent metastasis. However, the mechanisms underlying the role of exosomes in these processes remains elusive. The present study sought to determine the underlying mechanisms. Using two lung cancer cell lines, it was demonstrated that exosomes derived from metastatic small cell lung cancer cells (NCI-H1688) have greater effects on cancer cell migration, compared with exosomes derived from primary non-small cell lung cancer cells (NCI-H2228). Further characterization of the contents of the exosomes demonstrated that there were increased levels of TGF-β and IL-10 in exosomes from NCI-H1688 cells compared with exosomes derived from NCI-H2228 cells, in particular under hypoxia. Blockade of TGF-β and IL-10 with antibodies confirmed that these cytokines were essential for the regulation of cancer cell migration. Taken together, the results of the present study indicated that exosomes derived from cancer cells regulated the cellular migration of tumor cells through TGF-β and IL-10, which may provide a novel approach for developing therapeutic methods against cancer.

Background. Over the past decades, lots of advance have occurred in the prevention, diagnosis, and treatment of head and neck cancer (HNC). However, the contemporaneous incidence and survival trends, on the basis of population-based registry, have not been reported. Methods. The HNC cancer cases were accessed from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence trend was analyzed by joinpoint analysis, with the survival trend being analyzed by period analysis of relative survival rate (RSR) and Kaplan-Meier analyses. Cox regression analysis was performed to identify the prognostic factors for overall survival. Results. The general incidence trend of HNC increases slightly, with an average annual percentage change of 0.6%, along with five fluctuating segments. The improvement of net survival over the past decades was showed by increasing 60-month RSR, from 54.1% to 56.0% to 60.9% to 66.8%, which was further confirmed by Kaplan-Meier analyses. Moreover, disparities in incidence and survival patterns can be observed in different subgroups. Conclusion. A fluctuating incidence pattern and an ever-improving survival were observed in HNC over time.

BackgroundThe risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue.MethodsAn electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of bevacizumab.ResultsThirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05–1.57). This association varied significantly with tumor types (P = 0.002) and chemotherapeutic agents (P = 0.005) but not with bevacizumab dose (P = 0.90). Increased risk was seen in patients with non–small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum.ConclusionCompared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.

Nasopharyngeal carcinoma (NPC) is a leading cause of cancer-related mortality. Radiotherapy is one of the primary modalities for NPC treatment. However, in patients in the late stages of the disease, the local control rate and overall survival rate remain low. Therefore, it is urgent to identify new targets that can improve the outcome of radiotherapy in this neoplasm. In the present study, we investigated the effects of metformin on the radiosensitivity of NPC cells and explored the potential mechanisms. The radiosensitizing effects of metformin on NPC cells were measured by colony formation assay. Cell apoptosis was assessed by Hoechst 33342 staining analysis. DNA damage was detected by monitoring γ-H2AX foci with immunofluorescence. The changes in apotosis-related and DNA damage repair-related proteins were detected by western blotting. Our study demonstrated that metformin significantly reduced the cell viability, enhanced radiosensitivity and potentiated radiation-induced caspase-9/-3 cleavage in the NPC cells. In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, γ-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80. Therefore, our results suggest that metformin possesses a strong radiosensitizing potential in NPC cells. This radiosensitizing effect was associated with inhibition of DNA double-strand break repair processes through HR repair and the NHEJ repair signaling pathway, thereby enhancing radiation-induced cell apoptosis. These findings imply that metformin is a potent radiation-sensitizing agent and may be a promising candidate for clinical evaluation as part of a combined regimen for the treatment of nasopharyngeal carcinoma.

Abstract. In colorectal cancer (CRC), KRAS and BRAF mutations in primary tumors are associated with resistance to anti-epidermal growth factor receptor (anti-EGFR)-based therapies. However, the correlation between KRAS/BRAF mutation in primary tumors and serum has not been well studied. To evaluate the degree of concordance of KRAS/BRAF mutations between the primary tumors and the matched serum samples in CRC, serum and tumor tissues were collected from 115 patients with CRC and KRAS/BRAF mutations were examined by nested polymerase chain reaction (PCR) and direct sequencing. BRAF mutations were present in 3.5% (4/115) of the primary tumor tissue samples and 0.87% (1/115) of the serum samples. In the 4 primary tumors with BRAF mutations, identical mutations were not observed in the corresponding serum samples (κ=-0.016). KRAS mutations were observed in 32.2% (37/115) of the primary tumors and 11.3% (13/115) of the serum samples. Of the 37 tumor cases with KRAS mutations, 9 had identical mutations in the corresponding serum sample, with a concordance rate of 24.3% (9/37). Discordance was observed in 32 (27.8%) patients. The concordance between KRAS mutations in the primary tumors and KRAS mutations in the matched serums was low (κ=0.231). The results of the present study suggest that the possibility of differences in the mutational status of KRAS/BRAF between primary tumors and matched serum samples should be considered when patients are selected for anti-EGFR-based therapies.