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BACKGROUND: ß-thalassemia is an inherited hemoglobinopathy resulting in quantitative changes in the ß-globin chain. Understanding the molecular basis of that disorder requires studying the expression of genes controlling the pathways that affect the erythropoietic homeostasis especially the MAPK pathway. The MAPKs are a family of serine/threonine kinases that play an essential role in connecting cell-surface receptors to DNA in the nucleus of the cell. AIM: to study the effect of expression of GNAI2, DUSP5 and ARRB1 genes on MAPK signaling pathway in pediatric patients with beta thalassemia. METHODS: Forty children with beta thalassemia major (TM), forty children with beta thalassemia intermedia (TI) and forty age and gender matched healthy controls were enrolled in this study. Detection of GNAI2, DUSP5 and ARRB1 mRNA expression was done by real time polymerase chain reaction (RT-PCR). RESULTS: revealed increased expression of ARRB1 (Arrestin Beta 1) gene, and decreased expression of both GNAI2 (Guanine nucleotide-binding protein G (i) subunit alpha-2) and DUSP5 (Dual specificity protein phosphatase 5) genes in both patient groups than control groups respectively. CONCLUSIONS: Change in the rate of expression of ARRB1, GNAI2 and DUSP5 may have a role in the pathogenesis of abnormal hematopoiesis in cases of ß thalassemia through affecting the MAPK pathway.
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Accumulating evidence has revealed that livin gene and BCL-2 modifying factor (BMF) gene are closely associated with the initiation and progression of colon carcinoma by activating or suppressing multiple malignant processes. Those genes that can detect colon - cancer are a promising approach for cancer screening and diagnosis. This study aimed to evaluate correlation between livin, BMF and p53 genes expression in colon cancer tissues of patients included in the study, and their relationship with clinicopathological features and survival outcome in those patients. In this study, 50 pathologically diagnosed early cancer colon patients included and their tissue biopsy with 50 matched adjacent normal tissue, and 50 adenoma tissue specimens were analyzed for livin gene and BMF gene expressions using real time PCR. The relationship of those genes expressions with clinicopathological features, tumor markers, Time to Progression and overall survival for those patients were correlated in cancer colon group. In this study, there was a significant a reciprocal relationship between over expression of livin gene and down regulation of BMF and p53 genes in colon cancer cells. Livin mRNA was significantly higher, while BMF and p53 mRNA were significantly lower in colorectal cancer tissue compared to benign and normal colon tissue specimens (P < 0.001), however, this finding was absent between colon adenomas and normal mucosa. There was a significant association between up regulation of livin and down regulation of BMF and p53 expressions with more aggressive tumor (advanced TNM stage), rapid progression with metastasis and decreased overall survival in cancer colon patients, hence these genes can serve as significant prognostic markers of poor outcome in colon cancer patients. This work highlights the role of livin, BMF and p53 genes in colorectal tumorigenesis and the applicability of using those genes as a diagnostic and prognostic markers in patients with colon carcinoma and as a good target for cancer colon treatment in the future.
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BACKGROUND: Livin gene and Yes-Associated Protein 1 (YAP1 (play a pivotal role in organ size control and tumorigenesis. AIM: In the present pilot study, we investigate the expression of Livin gene and YAP1 in hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) compared to other HCV patients and controls.Methods: the studied patients were divided into three groups 30 patients in each group in addition to 30 healthy subjects as a control group. Relative quantification of Livin gene and YAP-1 were assessed by quantitative Real Time RT-PCR (qPCR) in all studied patients and healthy controls. other laboratory investigations were done including complete blood count (CBC),international normalized ratio (INR) as well as liver function tests and tumor markers. RESULTS: Significant overexpression of Livin gene and YAP-1 was detected in HCC group followed by Hepatitis C Virus (HCV) untreated group then HCV treated group. The relative quantitation (RQ) of both genes showed positive correlation to the carcinoembryonic antigen (CEA) level and a significant relation was found between higher level of Livin and YAP1 genes and tumor size. The overall survival rate was low in those patients with high levels of Livin and YAP 1 genes so they were considered as indicators of a bad prognosis. CONCLUSION: There is overexpression of Livin gene and YAP1 in hepatocellular carcinoma patients. They can be used as indicators of bad prognosis of the disease pathway together with low survival rate.
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BACKGROUND: 11ß HSD1 generates cortisol from cortisone. 11ß HSD1 single-nucleotide polymorphism (SNP) was associated with metabolic syndrome (MeTS). Although the relation of acne vulgaris (AV) and skin tags (STs) with MeTS has been reported, the relationship between 11ß HSD 1 SNP and cortisol activity in those patients has not studied till now. AIMS: To investigate, two 11ß-HSD1 SNPs (rs846910 and rs12086634), serum lipid profile and cortisol levels in patients with AV and STs in an Egyptian population. PATIENTS AND METHODS: This case-control study was performed on 50 patients having STs and 50 complaining of AV and 50 sex- and age-matched controls. We searched for serum lipid profile, cortisol levels, and 11ß-HSD1 rs846910 and rs12086634 SNPs using real time-PCR. RESULTS: Compared to controls,11ß-HSD1 rs846910 GA genotype carriers had significantly higher risks for developing AV and STs by 3.4- and 4.9-fold, respectively, and its A allele increases these risks by 3.1 and 4.4 times, respectively. Also, 11ß-HSD1 rs12086634 TG genotype increases the risk of AV by 3.2-fold, as well as STs by 3.5-fold, and its G allele increases the risk of AV by 3.2-fold and STs by 7-fold. In AV and ST patients, rs846910 GA genotype demonstrated significant associations with elevated body mass index (BMI), and cholesterol, low density lipoprotein (LDL), cortisol, and decreased high density lipoprotein serum levels, respectively. However, rs12086634 GG genotype was significantly associated with increased BMI, cholesterol, and LDL serum levels in patients with AV and STs, in addition to the number of STs and serum cortisol levels in ST patients. CONCLUSION: 11ß-HSD1 rs846910 and rs12086634 gene polymorphisms may contribute to AV and STs pathogenesis, that may be mediated through enhancing the enzymatic activity (increasing cortisol levels). AV and STs are associated with obesity and atherogenic lipid profile. Diagnosis of AV and STs may play a role in early detection of the MeTS.
