Genetic Variations of VEGFA Gene Are Associated With Infiltration of Adjacent Tissues and the Clinical Outcome of Patients With Nasopharyngeal Carcinoma
ANTICANCER RESEARCH
Authors: Psoma, Elizabeth; Koliou, Georgia-Angeliki; Dimitrakopoulos, Foteinos-Ioannis; Papadopoulou, Kyriaki; Rontogianni, Dimitra; Bobos, Mattheos; Visvikis, Anastasios; Kosmidis, Paris A.; Fountzilas, George; Constantinidis, Jannis; Kalogera-Fountzila, Anna
Abstract
Background/Aim: The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC). Patients and Methods: Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA -1154 G/A (rs1570360), -2578 A/C (rs699947), -1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS -671 A/G (rs1800682) was performed by using Sanger sequencing. Results: The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA -2578, VEGFA -1154 and VEGFA + 936 were significantly associated with infiltration to the pterygoid processes (p= 0.011, p= 0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA -2578 CC as compared to AC (HR=0.24, p=0.060). Conclusion: The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group.
A New Model Applied for Evaluating a Rhenium-diselenium Drug: Breast Cancer Cells Stimulated by Cytokines Induced from Polynuclear Cells by LPS
ANTICANCER RESEARCH
Authors: Veena, Vijay; Harikrishnan, Adhikesavan; Lakshmi, Basavegowda; Khanna, Sunali; Desmaele, Didier; Collery, Philippe
Abstract
Background/Aim: New anticancer drugs are usually tested on cancer cells in culture in a standard medium. We stimulated immune polynuclear cells by lipopolysaccharides to obtain an enriched medium (EM) containing inflammatory cytokines more closely reflecting the tumor microenvironment and tested a rhenium-diselenium (Re-diSe) drug in this new model. Concentrations of cytokines were compared with a control medium (CM). Materials and Methods: Human-derived breast cancer cells were grown in culture either in CM or EM with or without Re-diSe. Assays of tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL6), intereukin 1 beta (IL1 beta), transforming growth factor-beta (TGF beta), insulin growth factor 1 (IGF1) and vascular epidermal growth factor A (VEGFA) were performed by enzyme-linked immunosorbent assays. The production of reactive oxygen species (ROS) was determined by 2,7-dichlorofluorescein test. The cell growth was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests. Results: Concentrations of TNF alpha, IL6 and Il1 beta were observed to be significantly higher in EM than in CM. There was no difference for TGF beta, IGF1 and VEGFA. The cells were sensitive to Re-diSe, with reduced concentrations of TGF beta, IGF1, VEGFA and ROS, but the half-maximal inhibitory concentration was significantly higher in EM than in CM. Conclusion: The efficacy of the Re-diSe drug was confirmed in this model of aggressive cancer.