Apatinib combined with concurrent chemoradiotherapy in patients with subglottic small cell carcinoma: a case report.

Subglottic small cell carcinoma (SSMCC) is a rare type of neoplasm, meaning that laryngeal cancer guidelines in several countries, including the National Comprehensive Cancer Network (NCCN) guidelines, do not include treatment principles for SSMCC. Angiogenesis is an established factor in tumor initiation, growth, and dissemination. Apatinib mesylate, an orally administered drug, is a novel inhibitor of vascular endothelial growth factor receptor-2, a key mediator of angiogenesis, and has been shown to be safe and efficacious in the treatment of certain types of malignant tumors. To the best of our knowledge, there are few reports on the treatment of SSMCC with apatinib combined with concurrent chemoradiotherapy. In the present report of SSMCC in a 64-year-old woman, oral apatinib was given daily at a dose of 250 mg in combination with concurrent chemoradiotherapy; the only toxicities reported were mild leukopenia and finger numbness. Clear and rapid efficacy was observed with the disappearance of the tumor mass. Our findings indicate that apatinib combined with concurrent chemoradiotherapy may be effective in patients with SSMCC, with adverse reactions within the manageable range, thus representing an additional treatment option for this type of malignancy.

G­protein­coupled receptor 120 regulates the development and progression of human esophageal cancer.

The aim of the present study was to investigate the role of G­protein coupled receptor 120 (GPR120) in esophageal cancer and explore the related mechanisms. The expression of GPR120 in esophageal cancer tissues was examined by immunohistochemistry. Correlation analysis was performed to investigate the association between the level of GPR120 and clinical parameters. The expression of GPR120 was evaluated in esophageal cancer cell lines and the effects of GPR120 on cell proliferation, clone formation, migration and invasion were evaluated in an in vitro cell model and an in vivo ectopic tumor nude mice model. In addition, the effect of GPR120 on epithelial­mesenchymal transition (EMT), PI3K and I­κB pathway, as well as angiogenesis and inflammation­related cytokines was explored in order to elucidate the underlying mechanisms. Significantly increased expression of GPR120 was observed in esophageal cancer tissues compared to normal tissues. The expression of GPR120 was significantly related with histological grade, TNM stage and lymph node metastasis. GPR120 knockdown significantly decreased cell proliferation, clone formation, migration and invasion in vitro and decreased tumor growth in vivo. Furthermore significantly increased levels of E­cadherin and decreased levels of N­cadherin and vimentin, decreased level of Akt phosphorylation and I­κB phosphorylation, as well as decreased levels of vascular endothelial growth factor (VEGF), interleukin­8 (IL­8) and cyclooxygenase­2 (Cox­2) and its corresponding protein PGE2 were observed as the underlying mechanisms. In conclusion, we observed an increased level of GPR120 in esophageal cancer tissues, which served as a positive regulator of the development and progression of esophageal cancer. Multiple mechanisms including EMT, PI3K and I­κB pathway, as well as angiogenesis and inflammation­related cytokines were involved.

Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. METHODS: A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. RESULTS: The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. CONCLUSIONS: The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma.

Radiation therapy is one of the most important methods of contemporary cancer treatment. Cells in the G2 and M phases are more sensitive to radiation therapy, and cell division cycle 25 homolog C (CDC25C) is essential in shifting the cell cycle between these two phases. In this study, the knockdown of CDC25C in human esophageal squamous carcinoma EC9706 cells was mediated by transfecting shRNA against human CDC25C-subcloning into pGV248. The levels of CDC25C mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Moreover, cell proliferation and radiosensitivity were measured. Stable CDC25C-knockdown EC9706 cell lines were successfully established. Furthermore, the proliferation of both control and CDC25C-shRNA-EC9706 cells was inhibited after the cells were treated with increasing X-ray doses, and the proliferation of the control cells was affected more significantly (p<0.05). Moreover, cell colony formation assays allowed us to reach the same conclusion. Taken together, our experiments demonstrated that the knockdown of CDC25C can reduce both the radiotherapy sensitivity and the proliferation activity of EC9706 cells. Thus, CDC25C might be a potential biomarker for radiotherapy treatment.

Analysis of the efficacy of intensity-modulated radiotherapy and two-dimensional conventional radiotherapy in nasopharyngeal carcinoma with involvement of the cervical spine.

The aim of the present study was to retrospectively analyze the clinical efficacy and side-effects of two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated radiotherapy (IMRT) in 53 NPC patients with cervical spine involvement, without distant metastases. In total, 53 patients were enrolled in the present study, with 24 being treated with IMRT and 29 being treated with 2D-CRT. All 53 patients received platinum-based concurrent chemotherapy and 4-6 cycles of adjuvant chemotherapy subsequent to radiation. The patients were clinically staged according to the seventh edition of the UICC and AJCC staging systems. Overall survival (OS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) rates were calculated. The 3- and 5-year OS rates were 87.7% and 45.5% in the IMRT-treated group and 65.5% and 9.1% in the 2D-CRT-treated group (P=0.01). The 3- and 5-year LPES rates were 87.4% and 69.9% in the IMRT-treated group compared with 49.4% and 9.4% in the 2D-CRT-treated group, respectively (P=0.00). The 3- and 5-year DMFS rates were 94.4 and 40.8% in the IMRT-treated group and 79.8 and 30.4% in the 2D-CRT-treated group (P=0.13). N stage (P=0.00) and radiotherapy methods (P=0.01) were relevant to the OS and LPFS rates, it also revealed a significant difference when the DMFS rates were analyzed in N stage. The incidence of dry mouth in the IMRT group was significantly lower (P=0.01), but there was no statistically significant difference in acute oropharyngeal mucositis or myelosuppression. IMRT had significant advantages in local control and OS compared with conventional 2D-CRT, but IMRT failed to reduce the incidence of distant metastasis.