Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology

Breast cancer is characterized by cellular and molecular heterogeneity. Several molecular events are involved in controlling malignant cell processes. In this sense, there is an overriding importance to study the multiple cell alterations within this pathology. That the immune response can vary depending on sex is a widely identified fact. Steroid hormones and their receptors may regulate different functions and the responses of several subpopulations of the immune system. Few reports are focused on the function of estrogen receptors (ERs) on immune cells and their roles in different breast cancer subtypes. Thus, the aim of this review is to investigate the immune infiltrating tumor microenvironment and the prognosis conferred by it in different breast cancer subtypes, to discuss the current knowledge and to point out the roles of estrogen and its receptors on the infiltrating immune cells, as well as to identify how different immune subsets are modulated after anti-hormonal treatments in breast cancer patients

New Method to Disaggregate and Analyze Single Isolated Helminthes Cells Using Flow Cytometry: Proof of Concept

In parasitology, particularly in helminthes studies, several methods have been used to look for the expression of specific molecules, such as RT-PCR, western blot, 2D-electrophoresis, and microscopy, among others. However, these methods require homogenization of the whole helminth parasite, preventing evaluation of individual cells or specific cell types in a given parasite tissue or organ. Also, the extremely high interaction between helminthes and host cells (particularly immune cells) is an important point to be considered. It is really hard to obtain fresh parasites without host cell contamination. Then, it becomes crucial to determine that the analyzed proteins are exclusively from parasitic origin, and not a consequence of host cell contamination. Flow cytometry is a fluorescence-based technique used to evaluate the expression of extra-and intracellular proteins in different type cells, including protozoan parasites. It also allows the isolation and recovery of single-cell populations. Here, we describe a method to isolate and obtain purified helminthes cells

Progesterone Induces Scolex Evagination of the Human Parasite Taenia solium: Evolutionary Implications to the Host-Parasite Relationship

Taenia solium cysticercosis is a health problem in underdeveloped and developed countries. Sex hormones are involved in cysticercosis prevalence in female and male pigs. Here, we evaluated the effects of progesterone and its antagonist RU486 on scolex evagination, which is the initial step in the development of the adult worm. Interestingly, progesterone increased T. solium scolex evagination and worm growth, in a concentration-independent pattern. Progesterone effects could be mediated by a novel T. solium progesterone receptor (TsPR), since RU486 inhibits both scolex evagination and worm development induced by progesterone. Using RT-PCR and western blot, sequences related to progesterone receptor were detected in the parasite. A phylogenetic analysis reveals that TsPR is highly related to fish and amphibian progesterone receptors, whereas it has a distant relation with birds and mammals. Conclusively, progesterone directly acts upon T. solium cysticerci, possibly through its binding to a progesterone receptor synthesized by the parasite

A New Parasiticidal Compound inT. soliumCysticercosis

The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis

Sex Steroids Effects on the Molting Process of the Helminth Human Parasite Trichinella spiralis

We evaluated the in vitro effects of estradiol, progesterone, and testosterone on the molting process, which is the initial and crucial step in the development of the muscular larvae (ML or L1) to adult worm. Testosterone had no significative effect on the molting rate of the parasite, however, progesterone decreased the molting rate about a 50% in a concentration- and time-independent pattern, while estradiol had a slight effect (10%). The gene expression of caveolin-1, a specific gene used as a marker of parasite development, showed that progesterone and estradiol downregulated its expression, while protein expression was unaffected. By using flow citometry, a possible protein that is recognized by a commercial antiprogesterone receptor antibody was detected. These findings may have strong implications in the host-parasite coevolution, in the sex-associated susceptibility to this infection and could point out to possibilities to use antihormones to inhibit parasite development

Neuroimmunoendocrine Interactions in Tumorigenesis and Breast Cancer

Organism homeostasis is regulated through the tri-directional relationships between immune, endocrine, and nervous systems. These relationships are established by a complex network of chemokines, cytokines, hormones (peptide and non-peptide), neurotransmitters, and neurohormones that act onto its target cells, through common receptors. Despite initial attribution of the exclusive action of each molecule group (neurotransmitters, hormones, and cytokines), to the function of one specific system (nervous, endocrine, and immune, respectively), ligand and receptor pleiotropy and redundancy showed the multidirectional communication between systems. Cancer and metabolic and autoimmune diseases get established when homeostasis is disrupted. These interactions act in different disease levels, in cancer, since initial immunosurveillance phase, until immunosubversion and metastasis, in all cases is crucial for tumor development, cancer outcome, and patient prognosis

The Long Road to the Immunodiagnosis of Neurocysticercosis: Controversies and Confusions

To date, even widely studied, there is not a standard diagnostic method to detect neurocysticercotic patients. The later due to the complex nature of cysticercosis disease and the simplicity of common immunological assumptions involved in explaining the low scores and reproducibility of immunotests in the diagnosis of neurocysticercosis. To begin with, the few studies dealing with the immune response during neurocysticercosis are not conclusive, which of course it is crucial to develop an immunodiagnostic test. Their full recognition should clear confusion and reduce controversy as well as provide avenues of research and technological design. In here, logical arguments add that even under common immunological assumptions, serology of neurocysticercosis will always include false negative and positive results. Thus, serology is no strong support for medical diagnosis of neurocysticercosis (NC). In contrast, immunotests performed in the cerebrospinal fluid (CSF) of neurological patients should have fewer false positive and fewer false negatives than in serum. To conclude, it is argued that high scores in serology for NC will not yield to usual approaches and that success needs of a concerted worldwide effort. A more punctilious strategy based on the design of panels of confirmed positive and negative sera needs to be construed, shared and tested by all interested groups to obtain comparable results. The identification of a set of specific and representative antigens of Taenia solium (T. solium) and a thorough compilation of the many forms of antibody response of humans to the many forms of T. solium disease are also to be considered as one of the most importants factors to the disease