Glucose transporters (GLUTs) are required for glucose uptake in malignant cells, and they can be used as molecular targets for cancer therapy. An RT-PCR analysis was performed to investigate the mRNA levels of 14 subtypes of GLUTs in human colorectal cancer (COLO 205 and HT-29) and normal (FHC) cells. RT-PCR (n = 27) was used to assess the differences in paired tissue samples (tumor vs normal) isolated from colorectal cancer patients. GLUT2 was detected in all tested cells. The average GLUT2 mRNA level in 12 of 27 (44.4%) cases was 2.4-fold higher in tumor compared to normal tissues (*, p = 0.027). Higher GLUT2 mRNA expression was preferentially detected in advanced-stage tumors (stage 0 vs 3 = 16.38-fold, 95% CI = 9.22-26.54-fold; *, p = 0.029). The apple polyphenol phloretin (Ph) and siRNA methods were used to inhibit GLUT2 protein expression. Ph (0-100 μM, for 24 h) induced COLO 205 cell growth cycle arrest in a p53-dependent manner, which was confirmed by pretreatment of the cells with a p53-specific dominant negative expression vector. Hepatocyte nuclear factor 6 (HNF6), which was previously reported to be a transcription factor that activates GLUT2 and p53, was also induced by Ph (0-100 μM, for 24 h). The antitumor effect of Ph (25 mg/kg or DMSO twice a week for 6 weeks) was demonstrated in vivo using BALB/c nude mice bearing COLO 205 tumor xenografts. In conclusion, targeting GLUT2 could potentially suppress colorectal tumor cell invasiveness.
α-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4, *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced using the immunohistochemical staining H-score method (*P < 0.001). Statistical analysis revealed that lower FUCA1 levels significantly predicted an inferior overall survival rate among triple-negative breast cancer (TNBC) patients compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down MDA-MB-231 cell lines were established, and the results suggest that transient FUCA inhibition creates a selective pressure that triggers the metastasis of primary tumor cells, as detected by wound healing and invasion assays (*P < 0.01). The results suggest that FUCA1 may be a potential prognostic molecular target for clinical use, especially in TNBC patients.
The objective of the study was to evaluate the impact of a program based on the Teaching Personal and Social Responsibility (TPSR) on the variables of responsibility, basic psychology needs, motivation, satisfaction with life and the intention to be physically active, as well as the differences of gender. The participants were 85 students (experimental group n = 35, 17 girls and control group n = 50, 28 girls). The students of the experimental group received the TPSR for 8 months within the physical education subject. The findings indicated an improvement in the experimental group in terms of personal responsibility and in the case of female students, in basic psychological needs and intrinsic motivation. In conclusion, the TPSR program can be integrated into the physical education curriculum in order to improve the personal responsibility of students and fulfill their motivation and satisfaction of basic psychological needs.
Background:Accumulating data have found that adiponectin is involved in development of breast cancer (BC). However, these results were inconsistent.Method:A systematic search in PubMed, Embase, ISI Web of Science, and Chinese National Knowledge Infrastructure databases were conducted up to October 1, 2017. The standardized mean difference (SMD) with 95% confidence interval was applied to pool the effect size.Results:Finally, 31 eligible studies were included in this meta-analysis. The overall results indicated that serum adiponectin levels in BC cases were significantly lower than the controls (SMD = −0.33, P < 0.0001). As for the subgroup analysis of menstrual status, serum adiponectin levels were significantly lower in pre- and postmenopausal BC cases. Moreover, the subgroup analysis by ethnicity in pre- and postmenopausal group indicated an inverse association between adiponectin levels and BC risk in Asian population, but not in Caucasian population.Conclusion:The present meta-analysis suggests that low serum adiponectin concentration may be associated with an increased BC risk in premenopausal and postmenopausal women, especially among Asians. Adiponectin may serve as a biomarker of BC risk and help to identify subjects at high risk for BC development.
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