Glucocorticoid-induced apoptosis in lymphoid organs is associated with a delayed increase in circulating deoxyribonucleic acid.

Pathological processes like cancer, chronic inflammation and autoimmune phenomena, all of which involve massive cell death, are associated with significant increases in circulating DNA. In order to clarify whether massive apoptosis occurring under physiological circumstances also causes DNA release into the circulation, we correlated the time-course of dexamethasone-induced intra thymic cell apoptosis with plasma DNA dynamics in rats. Animals were given 10 mg/l dexamethasone in their drinking water for up to 7 days. Sequential plasma samples were obtained during the treatment and DNA was quantitated by a micro fluorometric assay. Thymus and spleen weight as well as apoptotic cell levels were assessed at different times. Seven days of glucocorticoid treatment reduced thymic and spleen mass by 82 and 31%, respectively. Intra thymic apoptosis was maximal 24 h after the beginning of glucocorticoid treatment, declining markedly by 48 h. Very little apoptosis was observed in the spleen. Plasma DNA increased steadily during the first 4 days of glucocorticoid treatment (11.8 +/- 1.2 microg/ml on day 0; 24.2 +/- 1.6 microg/ml on day 4) beginning to decline afterward. Thymectomy but not splenectomy, drastically reduced the glucocorticoid-induced increase in plasma DNA. It is concluded that hormone-induced massive intra thymic cell death is followed by a delayed release of nucleosomal DNA into the circulation.

Can breast cancer Hsp 27 (Heat Shock Protein 27000) expression influence axillary lymph node status?

The expression of heat shock protein 27 (Hsp 27) in breast cancers correlates with stage of disease, the lower the stage the higher the expression, and with the presence or absence of lymph node metastases; lymph node negative patients being more likely to express Hsp 27 (P<0.04).

Quantitative and functional study of breast cancer axillary lymph nodes and those draining other human malignant tumors.

Lymphocyte functional activity from lymph nodes draining human malignancies reflects the host immune response against tumour. Breast cancer is the neoplasia with the greatest amount of identified antigens but a weak inducer of a host efficient immune response. In our study we compared the mitogen stimulated-proliferative response of cells isolated from metastases-free lymph nodes draining breast cancer (Group 1), other malignant tumours (Group 2), and those obtained from patients without malignancies (Control group). A significant decrease of the proliferative response in cells isolated from lymph nodes draining breast cancer was observed comparing it to the other groups. Quantitative analysis of B and T cells showed a higher number of B cells than T cells in Groups 1 and 2. Moreover, Group 1 presented a two fold increase of T cells compared with Group 2. Our results suggest that the immunosuppression observed in lymph nodes draining breast cancer is higher than the inmunosuppression presented in other malignant tumours and that impaired function is not correlated with the increased number of T cells.

[Biology of heat shock proteins]. / Biologia de las proteinas del shock térmico.

Hsp (Heat shock proteins) are a family of constitutive proteins of all pro and eukariotic cells that play different physiological roles: they promote the folding (acquisition of tertiary structure) assembly, translocation and secretion of newly synthesized polypeptides and participate in the removal or repairing of denatured proteins acting as molecular chaperons. This family of proteins is composed by numerous members grouped according to their molecular weight. When cells are subjected to different stresses such as hyperthermic shock, radiation, toxins, viral infections, etc., Hsp are overexpressed. In this way, they exert a cytoprotective effect, making the cells resistant to apoptosis. In humans, Hsp are overexpressed in cancer cells from ovary, endometrium, breast, prostate, digestive tract, etc. In some cases, overexpression is correlated with an unfavorable outcome because these proteins could favour metastatic disease. Some authors associate them not only with proliferation but also with differentiation of the neoplastic tissue. Recent studies show their influence in resistance to chemotherapeutic drugs. In autoimmune diseases like rheumatoid arthritis, Hsp can suppress the inflammatory response. Nevertheless, their role in the immune system has not been well established.

[Dendritic cells and their role in pathology]. / Células dendríticas y su papel en patologia.

The aim of this review is to update the knowledge on dendritic cells (CD), as potent antigen-presenting cells (APC) expressing class II major histocompatibility (MHC) antigen. The different types of DC are derived from a common bone marrow precursor. They differentiate and migrate to lymphoid and non-lymphoid tissues under the influence of diverse stimuli. After binding antigen in their periphery they move to the lymph node activating T cells. Depending on the microenvironment, DC express several surface markers and secrete cytokines such as IL-12, Il-1 and TNF alpha. DC play a role in the pathogenesis of autoimmune and viral diseases being relevant in AIDS. These cells also infiltrate human tumors where they could be involved in the induction of anti-tumor immune response. The immunostimulatory properties of DC are currently applied in DC-based therapies of melanoma and lymphoma patients.

[Identification of a tumor antigen associated to the estrogen receptor in axillary lymph nodes of breast cancer patients]. / Identificación de un antigeno tumoral asociado al receptor estrogénico en ganglios linfáticos axilares de pacientes con cáncer mamario.

Sixteen axillary lymph nodes were incubated with sera from patients with mammary carcinoma. Using immunofluorescence staining sera recognized antigenic determinants on follicular dendritic cells (FDC) within the follicle centers. These results were confirmed with isolated and cultured FDC that were incubated with the same sera. All the results were negative with normal sera. We also found a cell population positively reacting with a monoclonal antibody against an estrogen receptor associated protein (ERAP) in subcapsular and cortical sinusae and germinal centers. Phenotype identification of ERAP+ cells indicated that they presented characteristics of macrophages and FDC respectively. Lymph nodes from other malignancies were negative for ERAP. These findings suggest that the tumoral antigen could be either the protein associated with the estrogen receptor or the receptor itself. The ERAP could be transported by the macrophages from the tumor to the regional lymph nodes where it could be processed and maintained during a long time by FDC, since it is known that these are the most efficient antigen presenting cells.

Effect of host-organ environment on the in vivo and in vitro behavior of a murine mammary adenocarcinoma.

We investigated the role that organ environment may play in determining the homing of disseminated cells from a murine mammary adenocarcinoma moderately metastatic to lung (M3). Conditioned medium (CM) from normal lung was able to enhance both local and metastatic growth. It increased the number of lung colonies when inoculated together with tumor cells via intravenous or separately via intraperitoneal route. Several in vitro studies were performed in order to elucidate possible mechanisms. It was shown that lung CM stimulated the in vitro growth and the migration of M3 cells. Normal kidney and liver CM lacked all these capacities.

Antibody-dependent Cytotoxicity of Human Platelets Against Trypanosoma Cruzi.

Human platelets in the presence of sera from humans with chronic Chagas' disease display cytotoxic activity against Trypanosoma cruzi (T. cruzi) trypomastigotes. Adsorption of IgE from those sera decrease the cytotoxic effect and IgG purified from the same sera revealed a cytotoxic action similar to the whole sera. Morphological studies suggest that chagasic serum promotes adhesion between parasites and platelets. On the basis of these results it is postulated that platelets may represent a defensive mechanism in South American trypanosomiasis by killing circulating forms of the parasite and that both IgG and IgE are relevant for that action.