Background: This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection.

Imatinib is a principal therapeutic agent for targeting colorectal tumours. However, mono-targeting by imatinib does not always achieve complete cancer eradication. Selenite, a well-known chemopreventive agent, is commonly used in cancer patients. In this study, we aimed to explore whether selenite can modulate imatinib cytotoxicity in colorectal cancer cells. HCT116 cells were treated with different concentrations of imatinib and/or selenite for 24, 48 and 72 hr. Imatinib-selenite interaction was analysed using isobologram equation. As indicators of apoptosis, DNA fragmentation, caspase-3 activity, Bcl-2 expression were explored. Autophagic machinery was also checked by visualizing acidic vesicular organelles and measuring Beclin-1 expression. Furthermore, reactive oxygen and nitrogen species were also examined. This study demonstrated that selenite synergistically augmented imatinib cytotoxicity in HCT116 cells as demonstrated by combination and dose reduction indices. Supranutritional dose of selenite when combined with imatinib induced apoptotic machinery by decreasing Bcl-2 expression, increasing caspase-3 activity and subsequently fragmenting DNA and blunted cytoprotective autophagy by decreasing Beclin-1 expression and autophagosomes formation. Moreover, their combination induced cell cycle S-phase block, increased total thiol content and reduced nitric oxide levels. In conclusion, selenite synergizes imatinib cytotoxicity through multi-barrelled molecular targeting, providing a novel therapeutic approach for colorectal cancer.Colorectal cancer (CRC) is the third most commonly diagnosed tumour type in males and the second in females worldwide [1]. Its annual incidence is expected to increase by nearly 80% over the next two decades in the less developed countries [2]. Imatinib mesylate, a tyrosine kinase small molecule inhibitor, has been studied for its therapeutic efficacy in the treatment of gastrointestinal stromal tumours (GISTs) [3] and CRC [4]. It was proven that imatinib inhibits chronic myeloid leukaemia (CML)-specific tyrosine kinase BCR-ABL and stem cell factor receptor (c-kit) [4]. However, c-kit mutation and over-expression associated with pro-angiogenic and anti-apoptotic responses resulted in compromised imatinib cytotoxicity and development of imatinib-resistant cancer cells [5,6]. It has also been reported that 45% of imatinib-treated patients experienced severe neutropenia requiring interruption of therapy or dose reduction ending in compromising patient outcome [7]. Thereby, several reports have described reduced effectiveness of imatinib as single agent for successful chemotherapy [4,7,8].The search for the underlying resistance mechanisms of imatinib has revealed that several interplaying mechanisms play vital roles. Although BCR/ABL point mutation, amplification and over-expression are frequently involved in imatinib and other tyrosine kinase inhibitors' resistance mechanisms [9], many other BCR/ABL-independent factors have been identified. These include decreased intracellu...

Introduction: Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 70% of infected patients, while 20-30% of patients recover spontaneously. This strengthens the role of the host genetic factors in either spontaneous or drug-induced viral clearance. The aim of this study was to investigate the relationship between interleukin-1β +3953 gene polymorphism and the response to interferon therapy in chronic HCV patients infected with genotype 4. Methodology: The interleukin-1β (+3953 C/T) (rs1143634) gene was amplified in 115 chronic HCV patients. Interleukin-1β single nucleotide polymorphism (SNP) plus several clinical and pathological factors were statistically analyzed in correlation with response to therapy. Results: Genotypes C/T and T/T had a significant association with non-response to treatment compared to genotype C/C, which had a strong association with response to treatment (95% confidence; 6.4884-48.5818, p = 0.0001). Furthermore, analysis of allele frequency in this cohort revealed that the T allele is associated with non-response, higher fibrosis, and higher hepatic activity, while the C allele had a significant association with sustained virologic response lower fibrosis, and lower hepatic activity (p value = 0.0001). Conclusion: This is the first study to examine the correlation between interleukin-1β (+3953 C/T) (rs1143634) gene polymorphism and the response of interferon therapy in genotype 4 HCV-infected patients. The results encourage further assessment of this SNP as a marker to predict response to therapy and disease progression, which can have major implications in saving money, time, and in avoiding unnecessary adverse effects.

AIM:To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio.METHODS:Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded.RESULTS:BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio.CONCLUSION:IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value.

Introduction. Hepatitis C virus (HCV) infection affects almost 3% of the world's population with the highest prevalence in Egypt (15%). The standard therapy; pegylated interferon (PEG-IFN) and ribavirin, is effective in only 60% of Egyptian patients; moreover it is costly, prolonged, and has severe side effects, so prediction of response is essential to reduce burden of unfavorable treatment. Several viral and host factors have been proved to affect response to the treatment PEG-IFN and ribavirin; the strongest of them is polymorphisms near IL28B; nonetheless, nonresponse in patients with favorable IL28B is still unexplained, which implies the importance of studying other immunological factors that may correlate with response. Interleukin 12 (IL-12) is one of the most important proinflammatory cytokine presented with the initiation of immune response, determining Th1 and Th2 differentiation. A functional single nucleotide polymorphism (A/C) at the 3′ untranslated region (3′UTR) at position 1188 (NCBI SNP database no 3212227) was reported to be associated with responding more efficiently to antiviral combination therapy in HCV genotype 1 infected patients. The present study aims to evaluate association between this polymorphism with fibrosis stages, necroinflammation activity, response to the combined therapy, and gender in Egyptian HCV genotype 4. Material and Methods. A total of 133 Egyptian chronic HCV (CHCV) patients were treated with IFN/RBV and were followed up. IL12B 1188 A/C genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) analysis. Results. A nonsignificant trend for higher sustained virological response (SVR) was observed in patients homozygote for IL12B 1188 A/C SNP CC genotype (69% SVR versus 30.8% NR) only but not in AC and AA genotypes. No association was detected between IL12B 1188 A/C polymorphism and less severe fibrosis or less liver activity. By stratification of response according to gender genotype, a significant difference in response between males and females was seen among AA genotype carriers only due to high number of non responder females. Conclusion. IL12B CC genotype appears to have some influence on SVR achievement but not on severe fibrosis and severe necroinflamation activity. Females carrying A/A genotype of IL12B 1188 A/C SNP achieve less SVR than those carrying AC and CC genotypes.