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Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell cancer, characterized by the highest mortality rate among other RCC subtypes due to the occurrence of metastasis and drug resistance following surgery. The Von Hippel-Lindau tumor suppressor (VHL)-hypoxia-inducible factor 1 subunit α (HIF1A)/hypoxia-inducible factor 2α (HIF2A)-vascular endothelial growth factor A (VEGFA) protein axis is involved in the development and progression of ccRCC, whereas sunitinib, a tyrosine kinase inhibitor, blocks the binding of VEGFA to its receptor. The aim of the present study was to examine the possible association of the gene expression of VHL, HIF1A, HIF2A, VEGFA and tumor protein P53 (P53) in cancer tissue with the outcome of ccRCC patients who were treated with sunitinib as first-line therapy following nephrec-tomy. A total of 36 ccRCC patients were enrolled, 11 of whom were administered sunitinib post-operatively. Tumor and control samples were collected, and mRNA and protein levels were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. High mRNA and protein expression levels of HIF2A and VEGFA were found to be associated with shorter overall survival (OS) and progression-free survival (PFS) rates, as well as with unfavorable risk factors of cancer recurrence and mortality. Resistance to sunitinib was also observed; the OS and PFS rates were shorter (median OS and PFS: 12 and 6 months, respectively, vs. undetermined). Sunitinib resistance was associated with high HIF2A and VEGFA protein levels (b=0.57 and b=0.69 for OS and PFS, respectively; P

The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25–75, with BMI 19.0–53.0 kg/m2 and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C–reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1–act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA–negative and OSA–positive patients (p < 0.05). Increased PON1–act was observed in the LL–genotype versus the LM + MM–genotype in the study population (p < 0.05). PON1–act was higher in the OSA–negative compared with OSA–positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1–act and LDL–cholesterol in the entire study population. The OSA–positive group presented an inverse relationship between PON1–act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.