RESUMO
Breast cancer is characterized by cellular and molecular heterogeneity. Several molecular events are involved in controlling malignant cell process. In this sense, the importance of studying multiple cell alterations in this pathology is overriding. A well-identified fact on immune response is that it can vary depend on sex. 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 prognosis conferred by it in different breast cancer subtypes, discuss the current knowledge and point out the roles of estrogens 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.
Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias da Mama , Estrogênios/imunologia , Proteínas de Neoplasias/imunologia , Receptores de Estrogênio/imunologia , Microambiente Tumoral/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologiaRESUMO
Endometriosis is a gynecological inflammatory and estrogen dependent pathology, defined as the presence of endometrial tissue outside the uterine cavity. The two most common symptoms of endometriosis are pelvic pain and infertility. This pain can be so intense that it affects the quality of life of women, from their relationships to their daily activities. Approximately 10% of women of reproductive age suffer from this disease. The main objective of this work was to investigate which immune system abnormalities present in patients with endometriosis that prevents ectopic endometrial tissue removal. Here we describe a series of changes in the different types of leukocytes, cytokines and factors that regulate the immune response seen in patients with endometriosis and the mechanisms by which these changes, not only favor "immunological tolerance" to the endometrial implants but at the same time stimulate the development of the disease by increasing cell proliferation and angiogenesis and inhibition of apoptosis ectopic endometrial tissue.
Assuntos
Endometriose/imunologia , Sistema Imunitário/fisiologia , Citocinas/imunologia , Estrogênios/imunologia , Feminino , Humanos , Leucócitos/imunologia , Peritônio/imunologiaRESUMO
The higher frequency of triple-negative and HER-2-positive tumors detected in younger patients has been suggested as an explanation for the more aggressive tumor types observed in this age group. However, estrogen receptor (ER)-positive tumors are the most frequent subtype of breast carcinomas identified, even in younger patients. In this retrospective study, the morphological and immunohistochemical profiles of ER-positive breast carcinomas from women 35 yrs and younger that were diagnosed between 1997 and 2007 were evaluated. From these cases, 213 were selected based on the availability of pathology reports and paraffin blocks. For comparison, 117 consecutive cases of breast carcinomas diagnosed in patients >60 yrs from 2006 were included. Paraffin-embedded tumors were stained for expression of ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), Ki-67 antigen, epidermal growth factor receptor (EGFR), cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays. ER-positive carcinomas were diagnosed in 120 (56.1%) samples of the younger patient group and in 92 (78.6%) samples of the older patient group. Of these ER-positive carcinomas, 48 (40%) from the younger patient group presented the subtype luminal A, compared with 53 (57.6%) from the older patient group (p=0.01). Tumors from the younger patient group were also associated with increased vascular involvement, co-expression of HER-2, and decreased expression of CD117. These results highlight differences in expression markers and the pathology of ER-positive tumors detected in younger women, with a notable characteristic being co-expression of HER-2.
Assuntos
Neoplasias da Mama/patologia , Estrogênios/imunologia , Marcadores Genéticos , Neoplasias Hormônio-Dependentes/patologia , Receptor ErbB-2/imunologia , Adulto , Neoplasias da Mama/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/imunologiaRESUMO
La Colestasis Gravídica en un síndrome que habitualmente se produce en el tercer trimestre del embarazo y se resuelve en el embarazo. Se caracteriza clínicamente por la presencia de prurito, ictericia o ambos sin otra disfunción hepática importante. En el siguiente trabajo se reporta caso de paciente femenino de 24 años III gestas II para FUR: 12/8/06 quien refiere de 6 días de evolución orinas coluricas, prurito generalizado predominio de manos y tórax, exámenes para clínicos con aumento de un transaminasas, fosfatasas alcalinas, se diagnóstica colestasis gravídica, patología de baja incidencia de 1/300 y 1/2000 embarazos, se considera importante realizar una revisión académica del mismo.
Assuntos
Humanos , Adulto , Feminino , Gravidez , Cálculos da Bexiga Urinária/etiologia , Colestase Intra-Hepática/patologia , Colestase Intra-Hepática/terapia , Monoéster Fosfórico Hidrolases/imunologia , Melanose/diagnóstico , Melanose/terapia , Urina/citologia , Período Pós-Parto/fisiologia , Prurido/diagnóstico , Transaminases/imunologia , Estrogênios/imunologia , Cirurgia Geral , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/patologia , Obstetrícia , Progesterona/imunologia , Sorologia/métodosRESUMO
Several clinical and experimental studies have demonstrated gender dimorphism in immune and organ responsiveness and in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses have been shown to be depressed in males following trauma-hemorrhage, whereas they were aintained/enhanced in proestrus females. Furthermore, sex hormones have been shown to be responsible for this gender-specific immune response following adverse circulatory conditions. More specifically, studies indicate that androgens produce immunodepression following trauma-hemorrhage in males. In contrast, female sex steroids appear to exhibit immunoprotective properties following trauma and severe blood loss. With regard to the underlying mechanisms, receptors for sex hormones have been identified on various immune cells suggesting direct effects of these hormones on the immune cells. Alternatively, indirect effects of sex hormones, ie, modulation of cardiovascular responses or androgen- and estrogen-synthesizing enzymes, might contribute to gender-specific immune responses. Recent studies indicate that sex hormones, eg, dehydroepiandrosterone (DHEA), also modulate the function of peripheral blood mononuclear cells in surgical patients. Thus, the immunomodulatory properties of sex hormones/receptor antagonists/sex steroid synthesizing enzymes following trauma-hemorrhage suggests novel therapeutic strategies for the treatment of immunodepression in surgical patients.
Assuntos
Hormônios Esteroides Gonadais/imunologia , Sepse/imunologia , Fatores Sexuais , Choque Hemorrágico/imunologia , Ferimentos e Lesões/imunologia , Adjuvantes Imunológicos/uso terapêutico , Antagonistas de Receptores de Andrógenos , Androgênios/imunologia , Circulação Sanguínea , Desidroepiandrosterona/imunologia , Desidroepiandrosterona/uso terapêutico , Suscetibilidade a Doenças , Estrogênios/imunologia , Feminino , Humanos , Imunocompetência , Masculino , Receptores Androgênicos/imunologia , Receptores Androgênicos/uso terapêutico , Receptores de Estrogênio/imunologia , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/fisiopatologia , Índices de Gravidade do Trauma , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/fisiopatologiaRESUMO
Several clinical and experimental studies have demonstrated gender dimorphism in immune and organ responsiveness and in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses have been shown to be depressed in males following trauma-hemorrhage, whereas they were aintained/enhanced in proestrus females. Furthermore, sex hormones have been shown to be responsible for this gender-specific immune response following adverse circulatory conditions. More specifically, studies indicate that androgens produce immunodepression following trauma-hemorrhage in males. In contrast, female sex steroids appear to exhibit immunoprotective properties following trauma and severe blood loss. With regard to the underlying mechanisms, receptors for sex hormones have been identified on various immune cells suggesting direct effects of these hormones on the immune cells. Alternatively, indirect effects of sex hormones, ie, modulation of cardiovascular responses or androgen- and estrogen-synthesizing enzymes, might contribute to gender-specific immune responses. Recent studies indicate that sex hormones, eg, dehydroepiandrosterone (DHEA), also modulate the function of peripheral blood mononuclear cells in surgical patients. Thus, the immunomodulatory properties of sex hormones/receptor antagonists/sex steroid synthesizing enzymes following trauma-hemorrhage suggests novel therapeutic strategies for the treatment of immunodepression in surgical patients.
Uma série de estudos clínicos e experimentais demonstram a existência de dimorfismo sexual das respostas imunológicas e orgânicas, bem como da suscetibilidade e morbidade em relação ao choque, ao trauma e à sepse. Respostas imunes celularmente mediadas apresentam-se deprimidas em machos em resposta ao binômio trauma-hemorragia, mas conservados/enaltecidos em fêmeas em proestro. Adicionalmente demonstra-se que os hormônios sexuais são responsáveis por esta dicomotomia de resposta sexualmente específica, em condições cardiovasculares adversas. Estudos específicos indicam que os andrógenos produzem imunodepressão pós-trauma hemorragia em machos. Em contraste, esteróides sexuais femininos parecem exibir propriedades imunoprotetoras após episódios de trauma com ou sem perda importante de sangue. No terreno dos mecanismos subjacentes, foram identificados receptores para hormônios sexuais em várias células do sistema imunológico, sugerindo a existência de efeitos diretos destes hormônios sobre tais células. Alternativamente, observam efeitos indiretos de hormônios sexuais tais como modulação das respostas cardiovasculares das enzimas sintetizadores de andrógeno e estrógeno, que podem contribuir para as estas respostas sexualmente diferenciadas. Estudos recentes indicam que os hormônios sexuais, como por exemplo a dehidroepiandrosterona também modulam a função de células mononucleares da série branca em pacientes cirúrgicos. Assim, as propriedades imunomodulatórias de hormônios sexuais/antagonistas de receptores/enzimas sintetizadores de esteróides após a ocorrência de trauma ou de hemorragia sugerem o caminho para novas estratégias terapêuticas para o tratamento de imunodepressão em pacientes cirúrgicos.
Assuntos
Humanos , Masculino , Feminino , Hormônios Esteroides Gonadais/imunologia , Caracteres Sexuais , Sepse/imunologia , Choque Hemorrágico/imunologia , Ferimentos e Lesões/imunologia , Adjuvantes Imunológicos/uso terapêutico , Androgênios/imunologia , Circulação Sanguínea , Suscetibilidade a Doenças , Desidroepiandrosterona/imunologia , Desidroepiandrosterona/uso terapêutico , Estrogênios/imunologia , Imunocompetência , Receptores Androgênicos/antagonistas & inibidores , Receptores Androgênicos/imunologia , Receptores Androgênicos/uso terapêutico , Receptores de Estrogênio/imunologia , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/fisiopatologia , Índices de Gravidade do Trauma , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/fisiopatologiaRESUMO
PROBLEM: We have previously demonstrated that the addition of placental interleukin-6 (IL-6) to murine hybridomas increased asymmetric antibody synthesis. Here we analyze whether progesterone (Pg) and estrogen (E2) affect asymmetric antibody synthesis by modulating IL-6 production in hybridoma cells. METHOD OF STUDY: Hybridoma 112D5 B cells were cultured with E2, Pg or recombinant IL-6. Cell proliferation was assessed by 3H-thymidine incorporation, and asymmetric antibodies were measured in culture supernatants by Con A fixation and enzyme-linked immunusorbant assay (ELISA). E2 and Pg-receptors (ER and PR) were evaluated in whole cell extracts by Western blot. IL-6 was measured in culture supernatants by ELISA. RESULTS: 112D5 expressed both PR and ER, which were differentially regulated. At 48 hr, Pg and E2 slightly decreased cell proliferation whereas IL-6 did not. As well as IL-6, 10(-10) M Pg but not E2 induced asymmetric antibody production. Interestingly, Pg at 10(-6) M decreased asymmetric antibody synthesis by hybridoma cells. Finally, mainly Pg but also E2 increased IL-6 synthesis, although IL-6 levels did not correlate with asymmetric antibodies synthesized in the presence of E2 or Pg. CONCLUSIONS: In cells expressing both ER and PR, we could demonstrate that steroids participate in humoral immune responses by modulating asymmetric antibody synthesis. IL-6 proved to be only partially involved. Other possible mechanisms involved in the effect of Pg on blocking antibody responses and their contribution to a successful pregnancy are discussed in the paper.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Estrogênios/imunologia , Interleucina-6/imunologia , Progesterona/imunologia , Animais , Divisão Celular/efeitos dos fármacos , Estrogênios/farmacologia , Hibridomas/efeitos dos fármacos , Hibridomas/imunologia , Técnicas In Vitro , Camundongos , Progesterona/farmacologia , Receptores de Estrogênio/biossíntese , Receptores de Estrogênio/imunologia , Receptores de Progesterona/biossíntese , Receptores de Progesterona/imunologiaRESUMO
Si bien el embrión tiene un programa genético de su propio desarrollo, para que se lleven a cabo el desarrollo y diferenciación embrionaria, así como la gestación normal, deben establecerse una serie de interacciones coordinadas entre el concepto y la madre, las cuales son mediadas por mensajeros químicos mediante mecanismo autocrinos, paracrinos y endocrinos. En el presente trabajo se analiza la participación de hormonas y factores réguladores de la implantación y el desarrollo de la unidad feto-placentaria