Modulation of vascular endothelium by imatinib: a study on the EA.hy 926 endothelial cell line.

In this study the EA.hy 926 endothelial cell line--simulating endothelial cells--was treated with imatinib in order to define a possible anti-angiogenic role for imatinib. Dose and time response experiments were performed. Cell morphology was studied, while migration efficiency, intercellular permeability and VE-cadherin expression were assayed, both in the presence and in the absence of imatinib. Imatinib-induced EA.hy 926 cell apoptosis was also examined. Results showed that imatinib reduced the endothelial cell population, changed cell monolayer morphology and reduced cell-to-cell cohesiveness. Migration efficiency was significantly decreased while intercellular permeability was 2.76-fold increased in the presence of imatinib. Indirect immunofluorescence microscopy showed nearly complete down-regulation of VE cadherin in imatinib-treated cells. Furthermore, apoptotic activity was detected in imatinib-treated cells. Altogether our results support an antiangiogenic profile for imatinib that possibly contributes to its therapeutic potential.

The distribution of S-100 protein in hyperplastic and neoplastic prostatic epithelium.

Specimens from 30 cases of benign prostatic hyperplasia and 75 cases of prostatic carcinoma obtained during suprapubic prostatectomy, transurethal resection of the prostate and radical prostatectomy, were stained immunohistochemically for S-100 protein, prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), neuron specific enolase (NSE) and polyclonal keratin. S-100 protein was positive in 9.3% of prostatic carcinomas and negative in all cases of prostatic hyperplasia. PAP and PSA were positive in all cases, while NSE was positive in 16% of the carcinoma cases. Polyclonal keratin was positive in both cell layers of the double layered hyperplastic prostatic epithelium with a more intense staining pattern in the outer cell layer. The authors believe that the S-100 protein immunoreactivity observed in some prostatic carcinomas, reflecting the change in the functional status of the neoplastic cells, might be of prognostic significance. They also emphasize the non-myoepithelial nature of the outer cell layer of the double layered prostatic epithelium.

Clinical implication of neuroendocrine differentiation in prostatic adenocarcinomas.

Specimens from 75 cases of prostatic adenocarcinoma of different M.D. Anderson degrees of malignancy were stained immunohistochemically for neuron-specific enolase (NSE), prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP). None of these tumors presented on hematoxylineosin sections any features suggesting neuroendocrine differentiation; nevertheless, 18.7% of the tumors were at least focally NSE positive. Because of the synchronous antigenic expression of the NSE-positive cells to PSA and PAP, the authors suggest that prostatic exocrine and neuroendocrine cells derive from a common precursor stem cell. The possibility of a more aggressive biological behavior of these tumors in comparison to the conventional carcinomas is discussed. The probable clinical necessity for a combined therapeutic approach is also investigated.

Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy.

Proliferating cell nuclear antigen (PCNA) is a nuclear protein maximally elevated in the S phase of proliferating and transformed cells and is recognized by the monoclonal antibody PC-10 in paraffin tissue sections. The liver regenerative process after partial hepatectomy in rats was estimated with the in vivo incorporation of [3H]thymidine into liver DNA and the liver thymidine kinase activity. The expression of PCNA in rat liver after partial hepatectomy was performed by immunohistochemical staining with PC-10 in paraffin embedded tissues, at different time intervals up to 240 hr. Proliferating cell nuclear antigen expression, [3H]thymidine incorporation into DNA, and liver thymidine kinase activity exhibited marked oscillations during the liver regenerative process. A close relationship was demonstrated among DNA synthesis, thymidine kinase activity, and PC-10 score. Our results suggest that PC-10 monoclonal antibody may be used as a worthwhile proliferation index in the evaluation of the rate of liver regeneration in rats.

Nucleolar organizer regions in prostatic adenocarcinomas. Comparison with flow cytometric analysis, tumor grade, stage and serum prostate-specific antigen levels.

Twenty-eight cases of prostatic adenocarcinomas have been selected and the mean argyrophil nucleolar organizer region (AgNOR) count for each case was evaluated. Nine of these tumors were of high, 13 of median and 6 of low differentiation. It was found that as the tumors became less differentiated, the AgNOR count increased (p less than 0.001). Stage of the disease, serum prostate-specific antigen (PSA) value, and DNA ploidy of all these cases have been examined as well but no statistically significant correlation among these three parameters and the AgNOR count was found.

Variation of vascular density within and between tumors of the uterine cervix and its predictive value for radiotherapy.

Vascular density in different regions of a number of uterine cervix carcinomas was determined by morphometric analysis of stained histologic sections. Variance analysis indicated a larger inter- than intra-tumoral inhomogeneity of the vasculature, suggesting a certain individual vascularization pattern in these tumors. As indicated by a retrospective study of archival biopsies, this pattern has a predictive value in regard to the efficacy of radiotherapy.