Clinical Effect of Apatinib Mesylate Tablets Combined with Paclitaxel Concurrent Radiotherapy and Chemotherapy in the First-Line Treatment of Locally Advanced Nasopharyngeal Carcinoma.

Objective: To explore the clinical efficacy and safety of apatinib combined with paclitaxel in the first-line treatment of locally advanced nasopharyngeal carcinoma. Methods: From March 2016 to June 2018, 114 patients with locally advanced nasopharyngeal carcinoma who received first-line treatment in our hospital were selected as the patient group, and those who received apatinib combined with paclitaxel concurrent radiotherapy and chemotherapy were selected as the research group (n = 54), while those who received paclitaxel concurrent radiotherapy and chemotherapy were selected as the control group (n = 60). Sixty healthy individuals in our hospital were recruited in the same period as the healthy group. The clinical effective rate, adverse reactions, 2-year overall survival rate (OS), 2-year progression-free survival rate (PFS), and quality of life were compared between the two groups, and the expression of miR-655 in the serum of each group was tested by RT-qPCR. Results: The total clinical effective rate of the research group was higher than that of the control group, and the 2-year OS and PFS of the research group were also higher than those of the control group (P < 0.05). Both groups of patients could tolerate the treatment, but the incidence of hypertension and proteinuria in the research group was higher than that in the control group (P < 0.05). The expression of miR-655 in the serum of patients was lower than that of the healthy group (P < 0.05). After treatment, miR-655 in serum increased in both the groups and miR-655 in the research group was higher than that in the control group (P < 0.05). The 2-year survival rate of OS and PFS in patients with low expression of miR-655 was significantly lower than that in patients with high expression of miR-655 (P < 0.05). Conclusion: Apatinib combined with paclitaxel concurrent radiotherapy and chemotherapy is effective and well-tolerated in the treatment of locally advanced nasopharyngeal carcinoma, which improves the quality of life of patients and can be popularized in clinical practice. In addition, the increase of miR-655 may be a target for treating nasopharyngeal carcinoma.

Circulating Tumor Cells and Fibronectin 1 in the Prognosis of Nasopharyngeal Carcinoma.

OBJECTIVE: Nasopharyngeal carcinoma is highly endemic in Southeast China. Circulating tumor cell is an important biomarker in the prognosis of variety kinds of cancers. Overexpression of fibronectin 1 was observed in variety kinds of malignancies and may contribute to progress and metastasis of the cancers. The current study was aimed to investigate phenotypes of circulating tumor cell in nasopharyngeal carcinoma blood and fibronectin 1 expression in the circulating tumor cell, and their clinical application in predicting nasopharyngeal carcinoma prognosis. METHODS: Blood samples were obtained from nasopharyngeal carcinoma patients before and after treatment. CanPatrol circulating tumor cell enrichment and RNA in situ hybridization were applied to identify circulating tumor cell and its phenotypes. Fibronectin 1 messenger RNA expression in the cells of circulating tumors was examined by messenger RNA-in situ hybridization. RESULTS: Circulating tumor cell was not associated with tumor characteristics or lymph node metastasis. Patients with >9 circulating tumor cells or >5 mesenchymal phenotype circulating tumor cell per 5-mL blood had poorer progression-free survival (P < .05). Multivariable analysis demonstrated that 2 or more mesenchymal phenotype circulating tumor cells with high fibronectin 1 messenger RNA expression predicted shorter progression-free survival (P < .05). CONCLUSIONS: Circulating tumor cells with high-level fibronectin 1 expression was associated with poor survival in patients with nasopharyngeal carcinoma and could be an independent prognostic factor for nasopharyngeal carcinoma.

Erastin decreases radioresistance of NSCLC cells partially by inducing GPX4-mediated ferroptosis.

The aim of the present study was to examine whether erastin influences radioresistance in non-small cell lung cancer (NSCLC) cells and produce a preliminary investigation into its mechanism of action. The radioresistant subtype of NSCLC cells, A549-R and H460-R, were induced by high-dose hypofractionated irradiation. Erastin was used to treat the radioresistant cells and radiosensitivity was examined by colony formation assays. Cell death was determined after the cells were treated with erastin, irradiation (IR) or erastin together with IR. The expression of glutathione peroxidase 4 (GPX4) expression in the parental cells and radioresistance cells was detected by western blotting. GPX4 expression in the radioresistance cells was subsequently inhibited, radiosensitivity and cell death was measured, and erastin enhanced radiosensitivity in A549-R and H460-R cells. Erastin and IR exhibited a combined effect on killing cells, as co-treatment with erastin and IR demonstrated a higher effect on killing cells compared with erastin or IR alone. GPX4 expression was inhibited by erastin in the radioresistant cells. Inhibiting GPX4 expression also radiosensitized NSCLC cells to radiation in the radioresistant cell lines. Erastin-induced and GPX4-inhibition-induced cell death could partially be rescued by deferoxamine, but not Z-VAD-FMK and olaparib, which indicated that erastin and GPX4-inhibition induced ferroptosis in the radioresistant cells. Erastin decreased radioresistance of NSCLC cells partially by inducing GPX4-mediated ferroptosis.

Niclosamide sensitizes nasopharyngeal carcinoma to radiation by downregulating Ku70/80 expression.

The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. CCK-8 assay was used to determine the effect of niclosamide on the proliferation of NPC cells. Colony formation assay was used to evaluate the radiosensitizing effect of niclosamide on NPC cells. Flow cytometry analysis was used to determine the apoptosis of NPC cells induced by niclosamide. Immunofluorescent staining was used to detect the formation of γ-H2AX foci and the localization of Ku70/80 proteins in NPC cells. Real-time PCR quantification analysis was used to examine the level of Ku70/80 mRNA. DNA damage repair-related proteins were detected by western blot analysis. Our results showed that niclosamide markedly suppressed the proliferation of NPC cells. Niclosamide pretreatment followed by irradiation reduced the colony forming ability of NPC cells. Niclosamide in combination with irradiation significantly increased the apoptotic rate of NPC cells. Niclosamide significantly reduced the transcriptional level of K70/80 but not the translocation of Ku70/80 protein induced by irradiation. In conclusion, our study demonstrated that niclosamide could inhibit the growth of NPC cells and sensitize the NPC cells to radiation via suppressing the transcription of Ku70/80.