Biomedical subjects

Juan Jose Mandoki

Publications and source records attributed to Juan Jose Mandoki.

4 recordsLinked to original sources

PubMed2006

Lung carcinomas decrease the number of monocytes/macrophages (CD14+ cells) that produce TNF-alpha.

The role that inflammation plays in cancer is puzzling. In peripheral blood, TNF-alpha-producing monocytes (CD14+ cells) were compared among patients with lung cancer, patients with tuberculosis and healthy donors; also, in pleural effusion TNF-alpha-producing CD14+ cells were compared between tuberculous patients and lung cancer patients. To analyze the level of the cellular alteration in TNF-alpha production, an experimental model was set up. TNF-alpha-producing CD14+ cells in peripheral blood from lung cancer patients were significantly lower than those from healthy donors. In pleural effusion, TNF-alpha-producing CD14+ cells were significantly lower in lung cancer patients than in tuberculous patients. Based on the results obtained from an experimental model, we suggest that this phenomenon was attributed to a reduced expression of TNF-alpha transcript. These findings provide evidence that lung carcinomas reduce TNF-alpha production by macrophages, possibly by inducing in these cells an M2 phenotype, which favor tumor progression.

Adenocarcinoma↗

PubMed2005

Effector, memory and naïve CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients.

The proportions of naïve, memory and effector CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients were studied. CD8+ T subsets were identified by using a combination of the following antibodies: anti-CD45RA, anti-CD45RO, anti-CD27 and anti-CD28, as well as antibodies to other markers. Fas-positive cells were determined in each CD8+ T subset. Also, the intracellular cytokine patterns of CD4+ and CD8+ lymphocytes from pleural effusion were analysed. In naïve, memory and effector CD8+ T subsets no significant differences were observed in peripheral blood between healthy donors and cancer patients. In contrast, a high proportion of cells with memory phenotype (CD45RA-CD45RO+CD27+CD28+) and a low proportion of cells with effector phenotype (CD45RA+CD45RO-CD27-CD28-) were found in pleural effusion with respect to peripheral blood (P<0.001). The altered proportions of CD8+ T subsets in pleural effusion were not mediated by type 2 cytokines produced by CD4+ or CD8+ lymphocytes. In the effector CD8+ T subset, from peripheral blood as well as from pleural effusion, a low percentage of perforin-expressing cells was observed compared to granzyme A-expressing cells. Additionally, a high percentage of naïve CD8+ T cells expressing Fas was found. Our data suggest that: (i) terminal-differentiation process of CD8+ T cells is blocked, and (ii) early Fas-expression in CD8+ T cells, which was reflected even in peripheral blood, may lead to apoptosis of naïve cells when they reach the effector stage. All these processes may contribute to the inadequate antitumour immune response found in lung carcinoma patients.

Adenocarcinoma↗

PubMed2005

Effects of single administration of diethylstilbestrol on murine langerhans cells.

Diethylstilbestrol (DES) is a synthetic compound with potent estrogenic actions useful in the treatment of prostate carcinoma despite the fact that it can also induce some forms of neoplasia. Both effects are thought to be related to its estrogenic actions and very little attention has been focused on the possible effect of DES on the immune response. Skin is the largest organ of the body and constitutes the first line of defense against xenobiotics. The Skin Immune System (SIS) has become the center of attention of research for the development of new therapeutic approaches for neoplasic diseases. Langerhans cells (LC), as an element of SIS, are "professional" antigen presenting cells resident in the skin that participate in the immune response associated with tolerance and acquired immunity to antigens. Hence in this work we studied the effect of DES on LC of murine skin as a model to analyze the possible effect of DES on the immune response. Male CD-1 mice (20 to 35 g body weight) were treated topically (TO) or subcutaneously (SC) with DES (10 and 100 mg/kg, dissolved in ethanol) and sacrificed at 12, 84 and 228 hr. LC were quantified in the ear skin of mice using both an enzymatic histochemical technique to demonstrate ATP-ase activity; and an indirect immunohistochemical assay for detecting class II molecules of the major histocompatibility complex (MHC-II). DES induced a significant time- and dose- dependent reduction in the number of LC (P < 0.05). Data presented here suggest that estrogens may exert a modulatory action on LC.

Adenosine Triphosphatases↗

PubMed2004

Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines.

Coumarin and 7-hydroxycoumarin have anti-tumour actions in vitro and in vivo. There are no previous reports on the cytostatic and apoptotic actions of coumarin and 7-hydroxycoumarin in non-small cell lung carcinoma (NSCLC) cell lines. Here we report on: (1) the inhibition of cell proliferation, (2) the phase in which cell cycle arrest occurs, and (3) the induction of apoptosis. Inhibition of cell proliferation was determined by 3H-thymidine incorporation. The effects on cell cycle phases were determined at 100 microg/ml of coumarin or 7-hydroxycoumarin using propidium iodide and flow cytometry. Higher concentrations were used to study apoptosis, detected by: (1) morphological cell changes, (2) subG1 peak detection and (3) Annexin-V assay. Peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin were used as controls. The actions of these compounds depended on drug concentrations and on histological cell type. Coumarin and 7-hydroxycoumarin inhibited cell growth by inducing cell cycle arrest in the G1 phase in all the lung carcinoma cell lines. Apoptosis required large concentrations of the coumarin compounds and was observed in adenocarcinomas. Apoptosis was not associated with intra-nucleosomal DNA fragmentation. Apoptosis was not observed in squamous lung carcinoma cell lines, but an increase in G1 cell cycle arrest was detected. In PBMC, only large concentrations of the coumarin compounds elicited a cystostatic action. Coumarins in combination with other anti-neoplastic drugs might increase the effectiveness of NSCLC treatments.

Adenocarcinoma↗