BackgroundHer2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients’ clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients’ in Saudi Arabia, and to explore its prognostic value in BC.MethodsA total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures.ResultsIHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient’s cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort.ConclusionThe study showed that 25 % of our patients’ cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.

BackgroundRecurrent pregnancy loss (RPL) or recurrent spontaneous abortion is an obstetric complication that affects couples at reproductive age. Previous reports documented a clear relationship between parents with chromosomal abnormalities and both recurrent miscarriages and infertility. However, limited data is available from the Arabian Peninsula which is known by higher rates of consanguineous marriages. The main goal of this study was to determine the prevalence of chromosomal abnormalities and thrombophilic polymorphisms, and to correlate them with RPL and consanguinity in Saudi Arabia.MethodsCytogenetic analysis of 171 consent patients with RPL was performed by the standard method of 72-h lymphocyte culture and GTG banding. Allelic polymorphisms of three thrombophilic genes (Factor V Leiden, Prothrombin A20210G, MTHFR C677T) were performed using PCR-RFLP (restriction fragment length polymorphism) and gel electrophoresis.ResultsData analysis revealed that 7.6 % of patients were carrier of numerical or structural chromosomal abnormalities. A high rate of translocations (46 %) was associated to increased incidence of RPL. A significant correlation between consanguineous RPL patients and chromosomal abnormalities (P < 0.05) was found. Both Factor V Leiden and Prothrombin A20210G allelic polymorphisms were significantly associated with a higher prevalence of RPL.ConclusionsThis study demonstrated a strong association between RPL and the prevalence of chromosomal abnormalities and inherited thrombophilia. Given the high rate of consanguineous marriages in the Saudi population, these results underline the importance of systematic cytogenetic investigation and genetic counseling preferably at the premarital stage or at least during early pregnancy phase through preimplantation genetic diagnosis (PGD).

BackgroundThe identification of charge clusters (runs of charged residues) in proteins and their mapping within the protein structure sequence is an important step toward a comprehensive analysis of how these particular motifs mediate, via electrostatic interactions, various molecular processes such as protein sorting, translocation, docking, orientation and binding to DNA and to other proteins. Few algorithms that specifically identify these charge clusters have been designed and described in the literature. In this study, 197 distinctive human viral proteomes were screened for the occurrence of charge clusters (CC) using a new computational approach.ResultsThree hundred and seventy three CC have been identified within the 2549 viral protein sequences screened. The number of protein sequences that are CC-free is 2176 (85.3 %) while 150 and 180 proteins contained positive charge (PCC) and negative charge clusters (NCC), respectively. The NCCs (211 detected) were more prevalent than PCC (162). PCC-containing proteins are significantly longer than those having NCCs (p = 2.10-16). The most prevalent virus families having PCC and NCC were Herpesviridae followed by Papillomaviridae. However, the single-strand RNA group has in average three times more NCC than PCC. According to the functional domain classification, a significant difference in distribution was observed between PCC and NCC (p = 2. 10−8) with the occurrence of NCCs being more frequent in C-terminal region while PCC more often fall within functional domains. Only 29 proteins sequences contained both NCC and PCC. Moreover, 101 NCC were conserved in 84 proteins while only 62 PCC were conserved in 60 protein sequences. To understand the mechanism by which the membrane translocation functionalities are embedded in viral proteins, we screened our PCC for sequences corresponding to cell-penetrating peptides (CPPs) using two online databases: CellPPd and CPPpred. We found that all our PCCs, having length varying from 7 to 30 amino-acids were predicted as CPPs. Experimental validation is required to improve our understanding of the role of these PCCs in viral infection process.ConclusionsScreening distinctive cluster charges in viral proteomes suggested a functional role of these protein regions and might provide potential clues to improve the current understanding of viral diseases in order to tailor better preventive and therapeutic approaches.

BackgroundPolycystic ovary syndrome (PCOS) is characterized by the growth of a number of small cysts on the ovaries which leads to sex hormonal imbalance. Women who are affected by this syndrome suffer from irregular menstrual cycles, decline in their fertility, excessive hair growth, obesity, acne and most importantly cardiac function problems. The vascular endothelial growth factor (VEGF) plays a pivotal role in tissue vascularization in general and in the pathogenesis of many diseases. The PCOS was found to be associated with high expression levels of VEGF. In women who undergo assisted reproductive procedures (ART), VEGF was found to be a key mediator of other factors to control ovary angiogenesis. Here, we set out to examine the association of VEGFA gene polymorphism with PCOS and its components in a population of Tunisia women to enhance our understanding of the genetic background leading angiogenesis and vascularization abnormalities in PCOS.MethodsThe association of VEGFA gene with PCOS and its components was examined in a cohort of 268 women from Tunisia involving 118 PCOS patients and 150 controls. VEGFA gene variations were assessed through the analysis of the following SNPs rs699947 (A/C), rs833061 (C/T), rs1570360 (G/A), rs833068 (G/A), rs3025020 (C/T), and rs3025039 (C/T). The linkage disequilibrium between SNPs was assessed using HAPLOVIEW software while combination of SNPs into haplotypes in the population and the reconstruction of the cladogram were carried-out by PHASE and ARLEQUIN programs, respectively. Genetic association and genotype-phenotype correlations were calculated by logistic regression and non-parametric tests (Kruskall-Wallis and Mann–Whitney tests), respectively, using StatView program.ResultsWe observed 10 haplotypes in our studied cohort whereH1 (ACGG), H2 (ACAG), H7 (CTGG) and H8 (CTGA) were the most frequent. We observed the association of the genotype CT of the SNP rs30225039 with PCOS phenotype (P = 0.03; OR 95 % CI = 2.05 [1.07–3.90]) and a trend for correlation of the pair of haplotypes H2/H2 with prolactin levels in plasma (P = 0.077; 193.5 ± 94.3 vs 45.7 ± 7.2). These data are consistent with literature and highlight one more time the role of vascularization in the pathogeny of PCOS.ConclusionsLD pattern in VEGF locus showed a similar LD pattern between the Tunisian population and the CEU. More haplotypes in the Tunisian population than in CEU was observed (22 haplotypes vs 16 haplotypes) suggesting higher recombination rate in Tunisians. The study showed that there was any advantage of using haplotypes compared with SNPs taken alone.

BackgroundHer2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients’ clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients’ in Saudi Arabia, and to explore its prognostic value in BC.MethodsA total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures.ResultsIHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient’s cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort.ConclusionThe study showed that 25 % of our patients’ cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.

BackgroundRecurrent pregnancy loss (RPL) or recurrent spontaneous abortion is an obstetric complication that affects couples at reproductive age. Previous reports documented a clear relationship between parents with chromosomal abnormalities and both recurrent miscarriages and infertility. However, limited data is available from the Arabian Peninsula which is known by higher rates of consanguineous marriages. The main goal of this study was to determine the prevalence of chromosomal abnormalities and thrombophilic polymorphisms, and to correlate them with RPL and consanguinity in Saudi Arabia.MethodsCytogenetic analysis of 171 consent patients with RPL was performed by the standard method of 72-h lymphocyte culture and GTG banding. Allelic polymorphisms of three thrombophilic genes (Factor V Leiden, Prothrombin A20210G, MTHFR C677T) were performed using PCR-RFLP (restriction fragment length polymorphism) and gel electrophoresis.ResultsData analysis revealed that 7.6 % of patients were carrier of numerical or structural chromosomal abnormalities. A high rate of translocations (46 %) was associated to increased incidence of RPL. A significant correlation between consanguineous RPL patients and chromosomal abnormalities (P < 0.05) was found. Both Factor V Leiden and Prothrombin A20210G allelic polymorphisms were significantly associated with a higher prevalence of RPL.ConclusionsThis study demonstrated a strong association between RPL and the prevalence of chromosomal abnormalities and inherited thrombophilia. Given the high rate of consanguineous marriages in the Saudi population, these results underline the importance of systematic cytogenetic investigation and genetic counseling preferably at the premarital stage or at least during early pregnancy phase through preimplantation genetic diagnosis (PGD).