Circ_0058063 regulates cell vitality and proliferation in oesophageal squamous-cell carcinomas.

Oesophageal squamous-cell carcinoma (ESCC) is a malignant tumor of the digestive system with a poor prognosis. Recent studies have shown the promoting effect of hsa_circ_0058063 (circ_0058063) on ESCC, but the potential regulatory mechanisms of circ_0058063 in ESCC remain largely unclear. The levels of circ_0058063, microRNA-4319 (miR-4319) and mRNA of thrombospondin-1 (THBS1) were indicated by quantitative real-time polymerase chain reaction in ESCC tissues and cells. Meanwhile, the level of THBS1 was quantified by western blot analysis. In addition, the cell functions were examined by CCK8 assay, Edu assay, flow cytometry assay and transwell assay. Furthermore, the interplay between miR-4319 and circ_0058063 or THBS1 was detected by dual-luciferase reporter assay. Finally, an in vivo experiment was implemented to confirm the effect of circ_0058063. The level of circ_0058063 and THBS1 were increased, and the miR-4319 level was decreased in ESCC tissues in contrast to that in normal tissues and cells. For functional analysis, circ_0058063 deficiency inhibited cell vitality, cell proliferation, migration and invasion in ESCC cells, whereas promoted cell apoptosis. Moreover, miR-4319 was confirmed to repress the progression of ESCC cells by suppressing THBS1. In mechanism, circ_0058063 acted as a miR-4319 sponge to regulate the level of THBS1. Besides, circ_0058063 knockdown also attenuated tumour growth in vivo. Circ_0058063 facilitates the development of ESCC through increasing THBS1 expression by regulating miR-4319, which also offered an underlying targeted therapy for ESCC treatment.

Hsa_circ_0014879 regulates the radiosensitivity of esophageal squamous cell carcinoma through miR-519-3p/CDC25A axis.

Circular RNAs (circRNAs) play critical roles in regulating the radiosensitivity of various cancers, including esophageal squamous cell carcinoma (ESCC). This research aimed to explore the role and potential mechanism of hsa_circ_0014879 in regulating ESCC radioresistance. The levels of hsa_circ_0014879, microRNA-519-3p (miR-519-3p) and cell division cycle 25A (CDC25A) were measured using quantitative real-time PCR or western blot. Cell proliferation was evaluated by colony formation assay. Cell migration and invasion were assessed by transwell and scratch assays. The levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot. Xenograft assay was used to analyze the effect of hsa_circ_0014879 on radiosensitivity in vivo. The binding relationship among hsa_circ_0014879, miR-519-3p and CDC25A was confirmed by dual-luciferase reporter assay. Hsa_circ_0014879 and CDC25A were upregulated, whereas miR-519-3p was downregulated in radio-resistant ESCC tissues and cells. Depletion of hsa_circ_0014879 suppressed the proliferation, migration and invasion of radio-resistant ESCC cells. Hsa_circ_0014879 knockdown elevated radiosensitivity of radio-resistant cells by modulating miR-519-3p. Moreover, miR-519-3p enhanced the radiosensitivity of radio-resistant cells by targeting CDC25A. Also, hsa_circ_0014879 upregulated CDC25A via sponging miR-519-3p. Hsa_circ_0014879 silencing enhanced the radiosensitivity of ESCC via regulating the miR-519-3p/CDC25A pathway.

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer.

OBJECTIVE: The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. METHODS: The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were re-evaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. RESULTS: Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. CONCLUSION: The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

Sesamin exerts anti-tumor activity in esophageal squamous cell carcinoma via inhibition of TRIM44 and NF-κB signaling.

Tripartite motif-containing 44 (TRIM44) is known to play an oncogenic role in multiple human cancers, including esophageal cancer. Sesamin possesses potent anti-inflammatory and anti-cancer properties for various cancers. This study is designed to unravel the biological functions of sesamin and TRIM44 in esophageal cancer. TRIM44 expression in esophageal squamous cell cancer (ESCC) cell lines and tissues was determined by RT-qPCR assay and Western blot. The effects of sesamin and TRIM44 on ESCC cell growth in vivo and in vitro were assessed by the mouse model and CCK-8 assay, respectively. We found that TRIM44 was significantly upregulated in ESCC cell lines and tissues when compared to their counterparts. Sesamin treatment or depletion of TRIM44 markedly reduced ESCC cell proliferation. The nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) signaling pathway may be involved in sesamin-mediated TRIM44 suppression. Finally, we showed that oral administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice. Our results suggest that sesamin exerts anti-tumor activity in ESCC via inhibition of NF-κB signaling pathway, demonstrating its potential for the treatment of esophageal cancer.

Pyrroloquinoline quinone induces chondrosarcoma cell apoptosis by increasing intracellular reactive oxygen species.

Pyrroloquinoline quinone (PQQ) has been reported to contribute to cancer cell apoptosis and death; however, little is known of its underlying mechanisms. The present study was designed to investigate the role of PQQ in chondrosarcoma cell apoptosis and the underlying mechanism. A cell cytotoxicity assay was used to detect cell death; flow cytometry analysis was also performed to determine cell apoptosis and intracellular reactive oxygen species (ROS). Biochemical methods were employed to detect the activity and the expression of superoxide dismutase (SOD)1, SOD2 and glutathione. The present study also examined the effect on tumorigenesis in vivo. The results demonstrated that the apoptosis of SW1353 cells induced by PQQ increased in a concentration­ and time­dependent manner, which may be attributable to the accumulation of intracellular ROS. In the in vivo experiments, PQQ inhibited proliferation and promoted apoptosis, increased ROS levels and caused DNA damage in transplanted cells. Taken together, the findings of the present study confirmed that PQQ induced apoptosis in human chondrosarcoma SW1353 cells and transplanted cells, by increasing intracellular ROS and reducing the ability of scavenging oxygen free radicals.

Expression and clinical significance of vascular endothelial growth factor and fms-related tyrosine kinase 1 in colorectal cancer.

The aim of the present study was to investigate the prognostic value of vascular endothelial growth factor (VEGF) and its receptor, fms-related tyrosine kinase-1 (FLT-1), in patients with colorectal cancer. An immunohistochemical approach was used to detect the protein expression of VEGF and FLT-1 in 90 patients with colorectal cancer. The impact of VEGF and FLT-1 tumor cell expression, in addition to other factors, on overall survival (OS) was retrospectively assessed in 90 patients. Multivariate analysis was performed in order to determine the prognostic significance of the factors. The positive expression rate of VEGF in the colorectal cancer tissues was 62.2% (56/90). The positive expression rate of FLT-1 in colorectal cancer tissues was 48.9% (44/90). The results of the log-rank test revealed that improved OS rates were significantly associated with the absence of VEGF expression (P<0.0001). By contrast, FLT-1 expression had no significant impact on OS (P=0.289). Upon multivariate analysis, VEGF expression (P=0.038) and clinical stage (P=0.021) maintained significance. VEGF expression proved to be an independent negative predictor of OS in patients with colorectal cancer. Conversely, FLT-1 expression demonstrated no impact on OS.

Phase II trial of concurrent chemoradiotherapy with S-1 versus weekly cisplatin for locoregionally advanced nasopharyngeal carcinoma.

This is a prospective randomized trial performed to compare the efficacy of concurrent chemoradiotherapy (CCRT) + S-1 (oral fluoropyrimidine) with that of CCRT + cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 105 eligible patients were randomly assigned to receive CCRT with S-1 (S-1 arm, n=50) or cisplatin weekly (control arm, n=55). Patients in the S-1 arm received CCRT plus S-1 (40-60 mg, twice daily for 4 consecutive weeks. Patients in the control arm received standard CCRT with weekly cisplatin. All the patients were included in an intention-to-treat survival analysis. Our results demonstrated that the S-1 and control arms did not differ significantly in terms of complete response, partial response, progression-free survival or overall survival (all P-values >0.05). However, the two arms varied significantly regarding certain grade 3-4 toxicities, including leukopenia, 5.5 vs. 22.0% (P=0.013); mucositis, 20.0 vs. 46.0% (P=0.004); dermatitis, 15.5 vs. 32.7% (P=0.011); and nausea, 9.1 vs. 41.6% (P<0.001) for the S-1 and control arms, respectively. In conclusion, CCRT with S-1 was found to be similar in efficacy but superior in terms of toxicity compared to the standard CCRT with weekly cisplatin.