Galunisertib promotes bevacizumab-induced vascular normalization in nasopharyngeal carcinoma: Multi-parameter MRI evaluation.

Tumor vascular normalization (TVN) is associated with antitumor therapeutic efficacy in nasopharyngeal carcinoma (NPC). However, the short time window of TVN is the biggest hindrance to its wide clinical application. We investigated whether targeting transforming growth factor beta can enhance the TVN effect of bevacizumab (BEV)-induced patient-derived xenograft (PDX) models of NPC. We constructed mouse subcutaneous PDX models of NPC and classified the mice into four drug-treatment groups, namely placebo control, galunisertib, BEV, and galunisertib + BEV. We performed MRI multi-parameter examinations at different time points and evaluated the vascular density, vascular structure, and tumor hypoxia microenvironment by histopathology. The efficacy of chemotherapy and drug delivery was evaluated by administering cisplatin. We found that combined therapy with galunisertib and BEV significantly delayed tumor growth, enhanced the TVN effect, and improved chemotherapeutic efficacy compared with monotherapy. Mechanistically, galunisertib reversed the epithelial-mesenchymal transition process and inhibited the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor by downregulating LAMC2. Correlation analysis of MRI data and pathological indicators showed that there was a good correlation between them.

Association of liver X receptor α (LXRα) gene polymorphism and coronary heart disease, serum lipids and glucose levels.

BACKGROUND: To explore the relationship between the liver X receptor α gene (LXRα) rsl2221497 polymorphism and the susceptibility of coronary heart disease (CHD) and serum lipids and glucose levels. METHODS: The single fluorescently labeled probes technique was used to detect the genotype of rsl2221497 in LXRα gene in 240 CHD patients and 250 healthy control subjects. The difference of genotype distribution between the two groups was analyzed using of Chi-square test. The serum lipids and glucose levels between the different genotypes were also compared. RESULTS: The risk of CHD in carriers with (AA + GA) genotype was 1.76 times as that in the GG genotype carriers (OR = 1.76, 95% CI: 1.18-2.87, P <0.05), and the risk of CHD in carriers with A allele increased 0.88 times compared to that in G allele carriers (OR = 1.88, 95% CI:1.21-3.43, P <0.01). Logistic regression analysis showed that after adjusting for other confounding factors, A allele was an independent risk for CHD. However, there were no differences in serum lipids and glucose levels between each genotype. CONCLUSIONS: The rsl2221497 polymorphism in LXRα gene was associated with susceptibility of CHD in Han population.