Improved sensitization effect of sunitinib in cancer cells of the esophagus under hypoxic microenviroment.

Radiotherapy is widely used in esophageal squamous cell carcinoma (ESCC) treatment. Promoting the radiation sensitivity of cancer cells is required. Recent studies have shown that sunitinib can inhibit the growth of several cancer lines. However, few studies on the radiosensitive effect of sunitinib on ESCC cells under hypoxic conditions have been conducted. In the present study, the radiosensitive effects of sunitinib on human ESCC cells were assessed, and the underlying mechanisms were explored. ESCC cells were exposed to hypoxia and treated with sunitinib at different concentrations prior to irradiation. Sunitinib potently inhibited ESCC cell proliferation in an MTT assay. In a clonogenic survival assay, sunitinib sensitized hypoxic ESCC cells to radiation, with sensitizing enhancement ratios of 1.31-1.59. In addition, sunitinib promoted the apoptosis of ESCC cells, but did not alter their cell cycle distribution. Radiosensitization was accompanied by inhibition of the radiation-induced upregulation of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression. Thus, sunitinib confers radiosensitivity to esophageal cancer cells, which is associated with the downregulation of HIF-1α and VEGF expression. Sunitinib can be a promising radiosensitizer for esophageal cancer radiotherapy.

Management of primary gastric small cell carcinoma in China.

BACKGROUND: Primary gastric small cell carcinomas (GSCCs) are increasingly identified by endoscopy, and account for 15-20% of all gastric neuroendocrine tumors (NETs). GSCCs have the worst prognosis with the highest rate of metastases. PURPOSE: To provide useful information for clinicians and researchers to better manage patients with GSCC, we studied the clinical features of GSCC and explored the corresponding therapies and prognosis. METHODS: A literature search was conducted through PUBMED, EMBASE, CNKI and WanFang Databases using search terms "stomach" or "gastric" and "small cell carcinoma" or "poorly differentiated neuroendocrine carcinoma", for the period 1999 to 2012. And the cases reported were all from China. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. RESULTS: Two hundred and five eligible cases were analyzed. The median age of patients was 62 years, with a male-to-female ratio of 5.4:1. Of the tumors, 53.17% were located in the upper stomach, 25.37% in the mid, 18.54% in the distal stomach, the remaining 2.93% were found in the total stomach. The mean size was 68mm in maximum diameter, with a range of 15-150 mm. Of the one hundred and thirty-five patients, fifty appeared to be pure GSCCs, eighty-five were mixed. The median overall survival time of 195 patients was 18.50 months. The 1-, 2-, and 5-year average survival rates of 142 patients were 66.75%, 37.13%, and 20.15%, respectively. CONCLUSIONS: GSCC is a rare tumor and it is notoriously aggressive with a strong propensity for both regional and distant spread. Therapies including surgical resection, chemotherapy, and local radiotherapy, by itself or in combination with other treatment, have been used to treat GSCCs in China. To identify the most effective treatment modalities for GSCCs, we still need prospective, multicenter, randomized clinical researches.

Relationship between TLR4 and NF-κB p65 protein expressions and clinical radiosensitivity of patients with esophageal squamous cell carcinoma.

OBJECTIVE: To study the relationship between TLR4 and NF-κB p65 protein expressions in tumor tissues after radiotherapy and clinical radiosensitivity of patients with esophageal squamous cell carcinoma. METHODS: A total of 93 patients with esophageal squamous cell carcinoma first treated in our hospital by radiotherapy and surgeries from November 2010 to December 2013 were selected. They were then divided into a severe reaction group, a moderate reaction group and a mild reaction group according to the postoperative pathological examination results of tumor tissues. The expressions of TLR4 and NF-κB p65 in the tumor samples were detected by Western blotting. RESULTS: Compared with the severe reaction group, the expression levels of TLR4 and NF-κB p65 in the moderate reaction group significantly increased (P<0.05). Similarly, the expression levels of the mild reaction group were significantly higher than those of the moderate reaction group (P<0.05). CONCLUSION: Reducing the expression levels of TLR4 and NF-κB p65 proteins may increase the radiosensitivity of patients with esophageal cancer.