BackgroundInfection with urinary schistosomiasis and its severity are oncogenic factors for developing carcinoma of the bladder, whether it is urothelial carcinoma (UC) of a transitional cell type (TCC) or non-urothelial of squamous cell carcinoma (SCC). In UC it is not defined whether it is schistosomal or not. This led to controversial results in expression of tumour markers, tumour prognosis, and response to therapy.ObjectivesWe assessed the application by immunohistochemistry method (IHC) for detection of schistosomal antigen in bladder cancer tissue samples to differentiate UC associated with or without schistosomiasis. Urothelial carcinoma stage, grade, and progression were correlated with the density, intensity, and index of schistosomal antigen expression. Follow up was done for 2-5 years.Design and participantsArchival tissue samples of 575 patients were studied: 515 urothelial carcinoma, 30 patients with SCC associated with schistosomiasis, and a control group of 30 patients without schistosomiasis.MeasurementsExpression of schistosomal antigen in tissue was done by IHC using monoclonal antibodies (MAbs) against schistosomal antigens (SA). Correlation of intensity of antigen expression to clinical and pathological data was analysed.Results and limitationsWe identified 3 parameters of antigen expression: density, intensity and index with 4 grades for each. SCC-group was 100% positive. UC was positive in 61.4% distributed as follows: Ta: 37.5%, T1: 62%, and muscle invasive T2-4 were 64%. Upstaging, metastases and recurrence were correlated with high index in T1 and T2-4 tumours.ConclusionUrothelial carcinoma associated with schistosomiasis was defined by the positive expression of schistosomal antigens in tissues detected by lHC using MAbs against schistosomal haematobium. Upstaging and progression of T1 and T2-4 were correlated with high density, intensity, and index of antigen expression. Non-schistosomal UC had negative expression for schistosomal antigen, which was detected in 36.5% of cases. These results would be of significance in differentiating schistosomal from non-schistosomal bladder cancer of UC and would predict the prognosis in T1, T2-3 tumours. Implementation of IHC using MAbs against SA in UC would help in planning the proper therapy. Schistosomiasis should be considered as an oncogene for UC in endemic areas.
Liver fibrosis is the wound-healing response of the liver to chronic injury it is very important to investigate different treatments and therapies for cirrhosis as the liver is one of the target organs for which stem cell-based therapeutics is very promising. In this study, Isolation, propagation, and characterization of unrestricted somatic stem cells (USSCs) from cord blood (CB) samples were performed and induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. The therapeutic potentiality of USSCs in two experimental models of chronic liver injury was evaluated. First experimental model (30 mice): Ten Schistosoma mansoni infected mice were intravenously injected with USSCs 1×10 6 cell/mouse. Ten were infected untreated (pathological control) and 10 healthy mice (negative control). 2nd experimental model (30 hamsters): Twenty were injected with repeated doses of carbon tetrachloride Sigma-Aldrich Chemical Co. (St Louis, Missouri, USA) to induce liver fibrosis; 10 were treated with intrahepatic injection of 3x10 6 USSCs and the other 10 were untreated pathological control. Ten healthy hamsters served as negative control. Animals were sacrificed 12 weeks post transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemical staining. Moreover, liver sections were examined for fibrosis levels. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes, and hepatocyte-like cells. In both models transplantation of CBUSSCs resulted in engraftment of the fibrosed livers with newly formed hepatocytes evidenced by positive immunostaining with human Hep Par1, α-fetoprotein, CK-18, CK-7 and OV6. Transplanted liver sections showed diminished hepatic fibrosis with significantly lower fibrotic index as well as significantly improved liver functions compared to the pathological control (p<0.001). Conclusion These data provide hope that human CB-derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis. This work is extracted from the project 1410 supported by the Science and Technology Development Funds (STDF),
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