Circulating MiRNA-373 as a Predictor of Response to Super-selective Transarterial Chemoembolization Bridging Therapy in Hepatocellular Carcinoma Patients Awaiting Liver Transplantation.

BACKGROUND: Super selective transarterial chemoembolization (TACE) has emerged as a bridging therapy for early hepatocellular carcinoma (HCC) patients awaiting liver transplantation. This study aimed at assessing the expression profiles of circulating MiR-210 and MiR-373 as potential predictors of response to TACE bridging therapy in a group of Egyptian HCC cases on top of chronic hepatitis-C infection, awaiting liver transplantation. METHODS: Fifty-three HCC cases awaiting liver transplantation referred for TACE, were followed up for three months, resulting in forty-five responders and eight non-responders based on modified response evaluation criteria in solid tumors (mRECIST). Circulating pre TACE MiR-210 and MiR-373 expressions were determined using reverse transcription quantitative polymerase chain reaction. RESULTS: Circulating pre TACE MiR-373, but not MiR-210, was significantly higher in non-responders than responders. Receiver operating characteristics (ROC) curve analysis of MiR-373, pre-TACE tumor volume, inflammatory score, and albumin bilirubin (ALBI) grade revealed highest sensitivity for pre-TACE tumor volume (cutoff>11.49 cm3) and highest specificity for pre-TACE MiR-373 (cutoff>1.46-fold change). Multivariate logistic regression revealed pre TACE MiR-373 as a significant independent predictor of TACE response after adjusting for pre TACE tumor volume. CONCLUSION: Circulating pre-TACE MiR-373 could assist as a noninvasive predictor marker of response to TACE bridging therapy in early HCC patients awaiting liver transplantation.

Relation of nitric oxide synthase gene (NOS3) polymorphisms to varicocele risk and post-varicocelectomy seminal oxidative stress reduction.

The pathophysiology of varicocele remains to be unknown. Several genetic factors have been implicated in varicocele etiopathogenesis. We studied the relationship between NOS3 c.894G>T, c.786T>C and 4b/a polymorphisms to varicocele risk and their prognostic value as regards improvement of the post-operative seminal parameters &/or seminal malonaldehyde levels. The three NOS3 polymorphisms were evaluated in 100 patients with varicocele and 100 healthy subjects by RT-PCR. Seminal plasma MDA level was measured pre-operatively and 3 months after varicocelectomy by the thiobarbituric acid method. The GT, TT, TC and bb genotypes of NOS3 polymorphism were more commonly observed in varicocele patients (30%, 9%, 28% and 70% respectively) compared to normal controls (12%, 0%, 10% and 50% respectively). The mean percentage of post-varicocelectomy seminal MDA reduction was highest with the GT genotype (p < .001). Genotypes GT+TT, TC and bb were associated with varicocele occurrence in our patients. The T (c.894G>T), C (c.786T>C) and b (NOS3 intron 4 VNTR) alleles were significantly associated with varicocele occurrence in our cohort of patients. We also report a better response regarding the reduction of seminal MDA after varicocelectomy with the GT and ba genotypes.

Study of microRNA Profile as a Molecular Biomarker in Egyptian Chronic Lymphocytic Leukemia.

MicroRNAs target mRNAs for cleavage or translational repression. They play a critical role in the progression of malignancies and leukemias including chronic lymphocytic leukemia (CLL). However, microRNA expression levels in Egyptian patients with CLL, and their prognostic value remain elusive. Our main aim was to assess the expression pattern of a panel of microRNAs in CLL patients to create an informative microRNA profile. The study subjects were 40 newly diagnosed CLL patients of both sexes and 40 age and sex matched controls. The expression levels of 12 microRNAs were evaluated by qRT-PCR, including miR-15a, 16, 23b, 24, 29a, 29c, 34a, 146a, 155, 181a, 195, and 221. Flow cytometry was used to determine the expression levels of BCL2, CD38, and ZAP-70 in CLL patients. We identified various degrees of upregulated miRNAs (miR-29a, miR-29c, miR-34a, miR-155, miR-146a, and miR-195) and down-regulated ones (miR-15a, miR-16, miR-23b, miR-24, miR-181a, and miR-221) in CLL patients relative to controls. The mean fluorescence intensity ratio (MFI-R) of BCL2 was recorded and was significantly upregulated in CLL patients compared with normal controls. In addition, inverse correlations were observed between microRNAs (miR-15a, miR-16, miR-155, and miR-195) and BCL2 MFI-R while positive correlations were observed between miR-29a and miR-29c, and BCL2 MFI-R. These findings suggest that these miRNAs regulate BCL2 levels. Moreover, we found that miR-15a, miR-16, miR-155, miR-181a, miR-195 and miR-221 were significantly upregulated, while miR-29a and miR-29c were significantly downregulated in ZAP-70 positive CLL patients. Various miRNAs may play an important role in the pathogenesis of CLL and have the potential to be used for the prognosis of patients with CLL.