Abstract : Background: Tumor cells have numerous immune surveillance escape mechanisms as well as means of res
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Abstract : Background: Tumor cells have numerous immune surveillance escape mechanisms as well as means of resistance to apoptosis. This study tried to clarify one of these mechanisms in bladder cancer with the hope of being able to develop targeted therapy that will sensitize the tumor cells to immune mediated apoptosis. Methods: In this study, light and electron microscopic examination and expression of TGF-beta-1protein and TGF-beta-R-1 receptor using immunocytochemical and immunoelectronmicroscopic techniques in urine and peripheral blood mononuclear cells (PBMNCs). Samples were obtained from 5 healthy controls (Group 1) and 60 patients are studied and classified according to the cytopathologic examination of their urine into 2 main subgroups: chronic cystitis (bilharzial and nonbilharzial, (Group 2, n = 15) and bladder cancer (transitional cell carcinoma and squamous cell carcinoma, (Group 3, n=45), whether associated with schistosomal infection or not associated. Results: Urine examination by both immunocytochemical and immunoelectronmicroscopic techniques revealed a statistically significant decrease in the percentage of positive cases expressing TGF-beta-R1 receptor in bladder cancer in comparison with either chronic cystitis cases or controls (P < .01), while TGF-beta-1 protein was significantly increased (P < .01). By light and electron microscopic examination, exfoliated necrotic malignant epithelial (urothelial) cells and many inflammatory cells were detected in malignant cases. Examination of PBMNCs by immunocytochemical and immunoelectronmicroscopic techniques showed a significant increase in the percentage of positive cases expressing both TGF-beta-1 protein and TGF-beta-R-1 receptors in bladder cancer in comparison to the control group (P < .01 and P < .05, respectively) and to chronic cystitis cases (P < .05). By light and electron microscopic examination, 42 out of 45 bladder cancer cases (93.3%) revealed remarkable apoptotic changes represented by cell shrinkage, surface blebs, nuclear chromatin condensation, and vacuolated cytoplasm. Conclusions: This work helps researchers and clinicians to better understand one of the escape mechanisms in bladder cancer that may facilitate the reverse of tumor escape from the immune system. It also draws attention to TGF-beta-1 protein and TGF-beta-R1 receptor; TGF-beta-1 protein can be used as attractive target for anticancer therapy, and the absence of TGF-beta-R1 can be considered a marker for malignant transformation of urothelial cells in bladder cancer. Key words: TGF-beta-1, TGF-beta-R-1, cytopathology, immunocytochemistry, cancer bladder, electron microscope. - Slides
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