👤 Gordon Ferns

Comprehensive molecular assessment of cancers could open up new horizons for novel therapies. Fibroblast growth factor receptor 1 (FGFR1) gene amplification has been previously demonstrated in non-small cell lung cancer (NSCLC) patients. The current study aimed to evaluate the prevalence of FGFR1 gene amplification and its association with clinical and demographic data in a group of NSCLC patients. The present study was performed on eighty-eight NSCLC patients who underwent bronchoscopy or surgery in Qaem Hospital, Mashhad, between 2010 and 2016. FGFR1 gene amplification was detected using real-time PCR assay on DNA extracted from paraffin-embedded tissue blocks of patients. Also, patients' clinical and demographic data, such as their survival, were evaluated. Statistical analysis was carried out using SPSS software. Seventeen (19.31%) out of eighty-eight patients with NSCLC presented FGFR1 gene amplification. Besides, we found a significant association between FGFR1 amplification and cigarette smoking (p-value= 0.01; OR: 4.08). Although cases with squamous cell carcinoma (SCC) showed a higher prevalence of FGFR1 amplification compared to adenocarcinoma patients, the difference was not statistically significant (p-value> 0.05). In addition, our findings showed no relationship between FGFR1 gene amplification and other clinical and demographic factors, including age, sex, grade, tumor operability, and survival. The frequency of FGFR1 amplification is estimated at 20% in the current study (26% in SCC versus 11% in adenocarcinoma; p-value= 0.07). Moreover, we found a direct association between FGFR1 amplification and cigarette smoking. However, no significant relationship with survival or other factors was observed. Show less

Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver. Show less

Cervical cancer is among the most aggressive gynecological tumors and is a consequence of interactions between genetic and epigenetic factors. Several genetic polymorphisms related to cervical cancer have been reported in previous clinical studies. In this study, we aimed to explore the possible relationship between polymorphisms of the ANGPTL4 gene locus and susceptibility to cervical cancer. We investigated the relationship between a single nucleotide polymorphism (SNP) in the ANPGTL4 gene (rs116843064) and risk of cervical cancer in a total of 378 individuals with (n = 151), or without (n = 227) cancer. DNA was extracted, and genotyped using a Taq-Man based real time PCR. The ANPGTL4 polymorphism was found to be associated with an increased risk of developing cervical neoplasia using dominant model (OR = 12.48, CI = 4.9-31.82, p < 0.0001) and additive model (OR = 30.54, CI = 7.35-126.89, p < 0.0001). Our results indicate that there is a strong association between ANPGTL4 and the susceptibility for cervical cancer suggesting that it is a potential risk factor for cervical neoplasia. Show less

Melanoma is a cancer that has a high mortality rate in the absence of targeted therapy. Conventional therapies such as surgery, chemotherapy, and radiotherapy are associated with poor prognosis. The expression of miR-21 appears to be of clinical importance, and the regulation of its expression appears to be an opportunity for treatment. In this current study, we aimed to evaluate the effects of miR-21 inhibition in- vitro and in-vivo. In-vitro studies have investigated LNA-anti-miR-21 in mouse melanoma cells (B16F10), and in-vivo studies have proposed a model of melanoma in male C57BL/6 mice. To evaluate the anticancer effects of LNA-anti-miR-21, a QRT-PCR analysis was performed using the 2 MiR-21 expression was inhibited by 80% after 24 h of B16F10 cell line transfection with LNA-anti-miR-21. The MTT test showed a significant reduction in the number of transfected cells with LNA-anti-miR-21. The transfected cells showed a significant increase in apoptosis in comparison with the control and scrambled LNA groups. According to our in vivo findings, anti-miR-21 could reduce tumor growth and volume in mice receiving intraperitoneal anti-miR after 9 days. The expression of the Show less

Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. The objective of this study was to investigate the association of ANGPTL4 gene variants (E40K) with fasting serum triglyceride levels and with cardiovascular risk factors, that included the presence of MetS in 817 subjects recruited from the Mashhad stroke and heart Atherosclerosis Disorders (MASHAD) cohort Study. ANGPTL4 genotypes were determined using a TaqMan genotyping based real time PCR method. The association of the genetic variant with the risk of metabolic syndrome and its relationship with lipid profile were determined. The frequency of GG, GA and AA genotypes were 96.9, 2.7 and 0.4% in individuals with MetS, and 78.8, 20.8, 0.4%, in those without MetS. The GA genotype of the rs116843064 polymorphism was associated with a lower risk for MetS (e.g., OR in Codominant genetic model: 0.14, 95% CI: (0.06-0.33), p < 0.0001). Subject with an A allele had a higher risk for MetS (OR: 6.72, 95% CI: (3.05-14.82), p < 0.0001). There was a significant difference in fasted lipid profiles across the genotypes for ANGPTL4. Carriers of the AG genotype had higher levels of serum HDL-cholesterol (HDL-C) and lower TG, compared to the GG homozygotes genotype. The G allele at the rs116843064 polymorphic locus of the ANGPTL4 gene was associated with a lower prevalence of MetS. Show less

Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl ester from HDL-C to LDL-C and VLDL-C. The aim of the present trial was to evaluate the effect of curcumin and its modified formulation on serum CETP concentrations in patients with metabolic syndrome. Participants were randomly allocated to one of three groups of 40 subjects receiving either unmodified curcumin or its phospholipid complex or placebo. Lipid profile and plasma CETP were measured at the start and six weeks after initiation of the treatment. The normality of data distribution was assessed by Kolmogorov-Smirnov test. Wilcoxon test was used for comparing the data before and after the intervention. The percent changes of CETP and biochemical factors among the three groups were compared using Kruskal-Wallis test. Serum CETP levels were not significantly altered among patients receiving curcumin. Curcumin and its complex had no significant effect on serum CETP concentrations. Show less

Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRα), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity. To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population. A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRα polymorphisms with the presence of obesity and overweight was assessed. There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85-2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity. This study revealed that there was no significant association between LXRα polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population. Show less

The metabolic syndrome (MetS) is considered to be a major risk factor for type 2 diabetes mellitus and cardiovascular diseases. It is characterized by central adiposity, high blood pressure, glucose intolerance and abnormalities of lipoprotein metabolism. The cause of MetS is likely to be due to a complex interaction between genetic and environmental factors. Liver X receptors alpha (NR1H3) and beta (NR1H2) play a key role in lipid and carbohydrate metabolism. The aim of this study was to investigate the contribution of genetic polymorphisms in the LXRs to risk of MetS and related traits. Two common SNPs in NR1H3 (rs11039155 and rs2279238) and in NR1H2 (rs17373080 and rs2695121) were genotyped using TaqMan assays in MetS patients (n=265) and controls (n=219). Logistic regression analyses were performed to calculate the odds ratios (ORs) as a measure of association of genotypes with the presence of MetS and related phenotypes. Although The NR1H2 polymorphism rs2695121 was nominally associated with MetS but correction for multiple-testing and adjustment for age, sex and number of MetS criteria, failed to identify any significant interactions associated with prevalence of MetS. However in the haplotype analysis, a LXRα haplotype AC, was more common in controls and was associated with a significant protective effect for MetS (OR [95% CI]=0.25 [0.07-0.88], p=0.031). In conclusion, this study suggests that the above-named variants in LXRα and LXRβ genes are not potential contributors to the risk of MetS and related traits in an Iranian population. Show less