Journal of Cytology & Histology

Background: Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme in the conversion of 5 ′ -deoxy- 5-fluorouridine (5 ′ -dFUrd), an intermediate metabolite of capecitabine (Xeloda ® ), to 5-fluorouracil (5-FU). We investigated the correlation between dThdPase activity and immunohistochemical staining in gynecological carcinoma and adjacent normal tissues. We hypothesize that the differential dThdPase activity between tumors and adjacent tissue is predictive of response to treatment with pyrimidine antimetabolites.

Methods: In 45 samples of carcinoma tissue and 35 of adjacent normal tissue from 45 patients, we measured dThdPase activity as well as immunoreactivity using an anti-dThdPase monoclonal antibody and macrophage and histiocyte-specific antibodies.

Results: dThdPase activity in tumor tissue was significantly higher than that in the corresponding adjacent normal tissue in all samples tested (12 uterine cervical, 19 endometrial, and 4 ovarian tumors). Anti-dThdPase immunopositivity was observed in the epithelial tumor cells of 76.9% of uterine cervical cancer samples, 60.0% of endometrial cancer samples and 63.6% of ovarian cancer samples. In stromal tissue, 84.6% of uterine cervical tumors (11/13), 90.0% of endometrial tumors (18/20), and 81.8% of ovarian tumors (9/11) were immunopositive for anti-dThdPase in interstitial cells (mainly macrophages). Macrophages were also strongly reactive in the stromal tissues of uterine cervical, endometrial, and ovarian cancers. The correlation between dThdPase activity and intensity of immunohistochemical staining of epithelial tumor cells with anti-dThdPase monoclonal antibody was statistically significant in endometrial carcinoma ( P = 0.008) but borderline in uterine cervical tumors ( P = 0.077). We found a good correlation between dThdPase activity and staining of epithelial tumor cells, particularly in the case of endometrial cancer.

Conclusions: We show that gynecological carcinomas show increased dThdPase activity, and this activity correlates with dThdPase staining of tumor epithelial cells. Thus, dThdPase staining of biopsy specimens could be useful in predicting the outcome of therapy with pyrimidine metabolites.

Background: The optimal stem cell source for regenerative therapy of the failing heart has not been settled. Embryonic stem cells, bone marrow derived cells, skeletal myoblasts, as well as cells derived from adult cardiac biopsies have been explored. Here we investigated the option to generate heart progenitor cells from the early human embryonic heart (hEHPCs) for the treatment of acute myocardial infarction. Methods: Two hearts (8 and 8.5 gestational weeks) from human abortion material were used for the clonal expansion of hEHPCs after stage specific embryonic antigen 1 (SSEA-1) enrichment by magnetic beads isolation. GFP-transduced hEHPCs- were transplanted into 18 SCID mice intramyocardially after induction of myocardial infarction. Hearts were harvested every 72 hours. Results: In this study we succeeded to isolate clones of hEHPCs with similar characteristics twice from two different early human embryonic hearts (8 and 8.5 gestational weeks) based on SSEA-1, a multipotent stem cell marker. Isolated clones were found to be positive for the multipotent stem cell marker (c-kit), the cardiac progenitors transcription factors GATA4, NKX2.5, TBX5 as well as the endothelial progenitors markers (CD133, CD34 and KDR). After transplantation into the peri-infarcted region they survived up to 12 days, and formed tubule-like structures in the mouse heart. Conclusions: These data demonstrate that the SSEA-1+ enriched cell population provides a potential basis to find the optimal cardiac progenitor cell population.

The protective effect of zinc (Zn) on the liver and kidney of albino rats exposed to intraperitoneal injection of cadmium chloride (CdCl2) was studied. Light microscopic examination for rats which were injected intraperitonealy with of 0.16 mg CdCl2/kg of body weight for 8 weeks indicated severe histological changes in both liver and kidney. In liver, a blurred trabecular structure, vacuolar degeneration and increased density of nuclear chromatin with very compact nuclear structure were found in hepatocytes. Moreover; mononuclear cell infiltrations and necrosis of single cells were also observed. In the kidney tubules, degeneration and hypertrophy of epithelial cells and dilation in the glomeruli were also observed. The effects of cadmium on the ultrastructures of both organs were studied. There are ultrastructural damages appeared in both organs as nuclear membrane damage, chromatin condensation, swelling of the mitochondria with regression of mitochondrial cristae, degranulation and disintegration of protein-synthesizing structures such as rough endoplasmic reticulum, increased number of lysosomes and ultimately cell death. Zn partially alleviated the damage observed in both the liver and kidney and differences in histological structure has been observed between the Zn-Cd and the control groups. Our results demonstrate the protective effect of ZnCl2 in prevention CdCl2- induced significant toxic pathological changes in the liver and kidney of the albino rats.