Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients.

AIM: Prostate cancer (PCa) is the second most common cancers in men worldwide. Its incidence can be influenced by several risk factors including genetic susceptibility. Therefore the search for the expression of a certain gene (ERG) and its rearrangement could give us clues for proper identification of PCa. And the study of ERG expression and its comparison to FISH in Egyptian patients can show whether ERG immunophenotype could be used instead of FISH, as it is cheaper. MATERIALS AND METHODS: This study was performed on 85 cases of PCa, showing 30 cases with HGPIN and 30 cases of prostatic hyperplasia. All were immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC TMRPSS2-ERG). RESULTS: ERG expression was found in 26% of PCa cases and 20% of HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases showing ERG immunoexpression). CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

The pharmacological approach to reverse portal hypertention and hepatic schistosomal fibrosis in Egypt, control experimental study.

Schistosoma mansoni is the most prevalent cause of liver fibrosis in Egypt. It is characterized by hepatocyte damage, inflammation and chronic parasite egg-induced granuloma formation leading to fibrosis. Its management, particularly fibrosis, has focused primarily on treating and preventing the complications of portal hypertension. Unfortunately, there is no therapy that has been proved to prevent progressive hepatic fibrosis which is associated with a significant morbidity and mortality due to granulomatous hypersensitivity to parasite eggs. However, recent developments in understanding hepatic fibrogenesis confirm that recovery from advanced fibrosis is possible. There is a considerable imperative to develop anti-fibrotic strategies that are applicable to liver fibrosis. It was noted that a marked increase in the amount of different interstitial collagens types are associated with the development of fibrotic liver diseases. Meanwhile, it has been suggested that as long as the relative portions of liver collagen are still within the normal limits, the fibrosis may still be reversible. If it exceeds the normal limits fibrogenesis will proceed to its end stage, even if the etiological agent is removed. Collagen type IV and procollagen type III are two of the most accurate fibrosis markers which allow reliable non-invasive diagnosis. The T lymphocytes and the immuno-regulatory cytokines may be important in the host response to S. mansoni granuloma formation and fibrosis. Chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Corticosteroids and prostaglandins interfere with both efferent and afferent mechanisms of immune function. These data indicate that this adjuvant therapy can be a candidate for therapeutic intervention in hepatic fibrosis through induction of a balance between Th1 and Th2 cells response as will be documented by the fibrosis markers. One hundred S. mansoni infected hamsters (150-250 gm) were obtained from the BRPU-TBRI (5 groups, 20 hamsters each). Treatment was started 10 weeks post infection. First G (20 hamsters) was neither infected nor treated, second G. was infected but untreated, third group infected and PZQ treated, forth G. infected and PZQ and MP treated and fifth group infected and PZQ and PgE1 treated. Samples (liver and blood) were obtained 20 weeks post infection. The serum level of: liver functions, procollagen type III, collagen type IV & Th1 cytokine (IL-2) and Th2 cytokine (IL-10) were performed. Histopathology was performed to study liver fibrosis, measuring the proliferate activity of the hepatocytes using cell image analyzer system and granuloma cells using the indirect immuno-histochemistry by monoclonal antibody proliferating cell nuclear antigen (PCNA). In this study, G.V showed high significant reduction in granuloma size, type and percentage of fibrosis and significant elevation in percentage of degenerated ova compared to Gs.III & IV. The proliferation index measured using PCNA showed high proliferative activity of hepatocytes in non treated group which declined in the treated Gs.III, IV & V. The proliferation activity of hepatocytes and granuloma forming cells decreased significantly in G.V compared to G.IV. There was a significant reduction in liver function tests even tendency for normalization in G.V compared to group III and IV. Procollagen type III and collagen type IV were significantly low in the serum in G.V compared to Gs.III & IV. Th1 (IL-2) level was significantly high in G.V compared to Gs.III, IV and Th2 (IL-10) was significantly low in G.V compared to Gs III & IV indicating the low amount of fibrosis was in the group treated with PZQ PgE1.PgE1 with PZQ to treat S. mansoni infected hamsters can modulate liver fibrosis and improves the liver function tests up to normalization. The balance between Th1 and Th2 cytokines level could be modulated to help reverse or decrease fibrosis in S. mansoni infected hamsters. This may pave the way for clinical application as combined therapy PZQ and PgE1 may by an effective approach to reverse hepatic fibrosis in schistosomiasis by the induction of dominant Th1 response.

Biocompatible dialysis membranes and oxidative stress in patients wih end-stage renal disease on maintenance haemodialysis.

Oxidative stress has been shown in (ESRD) patients specially those receiving regular haemodialysis (HD) in relation with an increased production of toxic free radicals due to membrane-induced complement leukocyte activation. An imbalance between oxidants and antioxidans has been suggested in uremic patients on HD. The respective influence of uremia and dialysis procedure has not been evaluated. Studies that have probed into the mechanism of oxygen radical production have implicated the bio-incompatibility of dialysis membranes. The effect of different dialysis membranes on lipid, lipoproteins, lipid peroxidation and total antioxidant capacity in ESRD patients on regular HD was studied. One hundred subjects were selected; 20 healthy controls, 20 chronic renal failure (CRF) patients on conservative drug management and 60 CRF patients on maintenance HD (20 dialyzed by polysulfone, 20 by hemophan and 20 by cuprophane membranes). All patients were matched for age, sex, gender and etiology of ESRD and HD patients for duration of dialysis. In addition to routine tests (Hb% and creatinine clearance in healthy control group and CRF patients on conservative management), total cholesterol, triglycerides, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B), serum malondialdehyde (MDA) and plasma total antioxidant status (TAS) were estimated. MDA was significantly higher and TAS was lower in uremic patients treated conservatively or by HD than in controls. MDA was significantly higher in HD than CRF patients on conservative management with least significant difference in HD patients treated by polysulfone followed by hemophan and then cuprophane membrane, while only cuprophane group showed lower levels of TAS compared to CRF patients on conservative management. HDL-C and Apo A was higher in polysulfone and hemophan than cuprophane group while triglyderide was lower. Polysulfone group showed lower levels of LDL-C than both cuprophane and hemophane groups thus providing less atherogenic lipid profile. There was a positive correlation between Hb% and TAS and a significant negative correlation between MDA and Hb%. There was a significant negative correlation between TAS and duration of dialysis in HD patients. In CRF patients on conservative management we obtained a significant positive correlation with TAS and a significant negative correlation with MDA.