Interferon-alpha inhibits proliferation and induces apoptosis of merkel cell carcinoma in vitro.

Merkel cell carcinoma is a tumor with aggressive biological behavior and limited response to chemotherapy. The present study investigated the effect of interferon (IFN)-alpha on growth and apoptosis of Merkel carcinoma cells in vitro. Proliferation of MCC-1 cell line was reduced dose-dependently by IFN-alpha and diminished when higher IFN-alpha concentrations were used. Additionally, IFN-alpha potently decreased DNA-synthesis and Ki67/MIB-1 proliferation index of MCC-1 cultures. Furthermore, IFN-alpha induced dose-dependently apoptosis of MCC-1 cells as shown by caspase-3 activation, and detection of apoptotic DNA strand breaks and fragmented nuclei. These findings suggest that IFN-alpha may have antitumor activity against Merkel cell carcinoma.

Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: study in paraffin tissue sections.

BACKGROUND: Steroid action is mediated, in addition to classical intracellular receptors, by recently identified membrane sites, that generate rapid non-genomic effects. We have recently identified a membrane androgen receptor site on prostate carcinoma cells, mediating testosterone rapid effects on the cytoskeleton and secretion within minutes. METHODS: The aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone. RESULTS: We report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleason's microscopic grading score system. CONCLUSION: We conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens.

Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. A common feature is the presence of microscopic areas of epithelial cell dropout. Increased apoptosis of these cells could elucidate the speculative pathogenesis of the disease. Therefore, the aim of our study was to examine the expression of p53, p21, bcl-2, bax, and caspase-3 in association with DNA strand breaks in bronchial and alveolar epithelial cells in lung specimens from IPF patients and control subjects. PATIENTS AND METHODS: We examined by immunohistochemistry the expression of p53, p21, bax, bcl-2, and caspase-3 in association with DNA strand breaks detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) in bronchial and alveolar epithelial cells in lung specimens taken by biopsy in 12 IPF patients and 10 control subjects. An independent tissue evaluation by two pathologists graded semiquantatively the degree of staining present. RESULTS: TUNEL was positive in epithelial cells in all IPF patients and only in one control subject. The expression of p53, p21, bax, and caspase-3 was up-regulated in IPF patients compared to control subjects. Bcl-2 was expressed less in IPF patients than in control subjects. CONCLUSIONS: These results confirm that apoptotic hyperplastic epithelial cells are present in patients with IPF and that the expression of p53, p21, bax, and caspase-3 appears to be up-regulated and that of bcl-2 down-regulated in these cells. The increased expression of proapoptotic molecules in epithelial cells in IPF may be involved in the inadequate and delayed reepithelialization, which in turn contributes to fibroblast proliferation.