Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma.

Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 µg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

Proliferative Properties of 17ß-aminoestrogens in MCF-7 Human Breast Cancer Cells.

The 17ß-aminoestrogens (AEs) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E2 ) which presents pro-coagulant effects, potentially thrombogenic. They possess anti-anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF-7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AEs' proliferation properties were evaluated compared with E2 in MCF-7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co-incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP (ERα) and PHTPP (ERß). E2 and AEs increased MCF-7 cell proliferation; their proliferative effect was between 1.5-2 and E2 = 3.6 compared with controls (0); their relative proliferative effect was 18-38% (E2 = 100%) with a relative proliferative potency of 4.5-8.9 (E2 = 100). The ERα antagonist MPP inhibited the MCF-7 cell proliferation induced by E2 and AEs; on the contrary, the ERß antagonist PHTPP exacerbated the proliferative response, showing that the AEs' proliferative activity was mainly ERα-mediated and apparently controlled by ERß. Preliminary cytometric DNA flow analysis showed that AEs' cell cycle S phase inducer property was lower than E2 following the proliferative order: E2 > butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT.

4-Hydroxycoumarin disorganizes the actin cytoskeleton in B16-F10 melanoma cells but not in B82 fibroblasts, decreasing their adhesion to extracellular matrix proteins and motility.

This study determined the in vitro effects of 4-hydroxycoumarin (4-HC) employing the melanoma cell line B16-F10 and the non-malignant fibroblastic cell line B82. 4-HC disorganized the actin cytoskeleton in B16-F10 cells, but not in B82 fibroblasts. Cytoskeletal disorganization correlated with reductions in cell adhesion to four extracellular matrix proteins and inhibition of random motility. 4-HC did not modify cell viability or actin expression, but decreased tyrosine phosphorylation of several proteins in melanoma cells. Because adhesion of tumor cells to extracellular matrix is required during the metastatic process, 4-HC might be useful as an adjuvant therapy for melanoma.

Anormalidades en el sistema adhesivo de neoplasias pulmonares / Abnormalities in adhesión system of pulmonary neoplasms

La progresión de una neoplasia pulmonar requiere alteraciones en la expresión de moléculas de adhesión en la célula tumoral. Un decremento en la expresión de E-cadherina y de las cateninas a y b disminuye la adhesión homotípica e incrementa el número de células neoplásicas liberadas del tumor primario. Las integrinas presentan cambios complejos en su expresión; la capacidad invasiva se ve favorecida por el aumento en la expresión de unas integrinas, como la a 2b 1 y por la disminución en la expresión de otras, como la a 3b 1. Los cambios en la expresión de ICAM-1 favorecen la evasión de la respuesta inmune. La disminución en la densidad de ICAM-1 en la superficie de células tumorales disminuye la posibilidad de contacto célula-célula. El aumento en la concentración de la isoforma soluble de ICAM-1 bloquea los contrarreceptores presentes en las células inmunológicas. También se han identificado alteraciones en moléculas que modulan la adhesión, como FAK y paxilina. Las moléculas de adhesión y los componentes regulatorios de la adhesión, pueden ser blancos farmacológicos para el desarrollo de nuevas terapias adyuvantes para el tratamiento del cáncer.