RESUMO
Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.
Assuntos
Neoplasias da Mama/prevenção & controle , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Neoplasias Ovarianas/prevenção & controle , Neoplasias da Mama/genética , Terapia de Reposição de Estrogênios , Feminino , Triagem de Portadores Genéticos , Aconselhamento Genético , Humanos , Mutação , Neoplasias Ovarianas/genética , Medição de Risco , Fatores de Risco , Salpingo-OoforectomiaRESUMO
The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.
Assuntos
Córtex Suprarrenal/imunologia , Aldosterona/imunologia , Imunomodulação/imunologia , Inflamação/imunologia , Modelos Imunológicos , Receptores de Mineralocorticoides/imunologia , Animais , Humanos , Fatores Imunológicos/imunologiaRESUMO
BACKGROUND: Restenosis post stenting is due to the deposit of extracellular matrix, mainly collagen in the neointima. Controversy exists regarding if collagen is generated locally or by immigration from the adventitia. AIM: To study the fibrocellular response after stent implantation in rabbit iliac arteries. To observe, by immunohistochemistry and in situ hybridization, if collagen type I mRNA is expressed in the neointima, in the media or in the adventitia. MATERIAL AND METHODS: Thirty eight white rabbits (New Zealand) of 4 kg received an hypercholesterolemic diet during 1 month. After this period, in all but 6 of them, an angioplasty with stent implantation was performed via right carotid artery in both iliac arteries, using a 1:1.3 relationship regarding the reference vessel. Angiograms were performed at day 0, 4, 21, and 40, followed by paraffin fixation of the injured segments, immunohistochemistry for alpha-actin and in situ hybridization to detect procollagen type I (alpha 1R1) mRNA. RESULTS: No hybridization was observed in non injured arteries or at day 0 (n = 6). Expression of alpha 1R1 mRNA was observed in the neointima starting at day 4 after stenting (n = 8). At day 21 (n = 8) hybridization of procollagen type I was not only observed in the neointima, but also in the media, which became equally intense in both areas. At day 40 (n = 6) hybridization was observed similarly in the media and adventitia. CONCLUSIONS: In this model, hybridization of procollagen type I started in the neointima, then involved the media and finally the adventitia. This finding might be useful for designing therapies to be delivered locally at the end of an angioplasty to prevent collagen deposition in the neointima.
Assuntos
Colágeno Tipo I/análise , Oclusão de Enxerto Vascular/metabolismo , Artéria Ilíaca/metabolismo , Pró-Colágeno/análise , Túnica Íntima/metabolismo , Angioplastia com Balão , Animais , Oclusão de Enxerto Vascular/patologia , Artéria Ilíaca/cirurgia , Imuno-Histoquímica , Hibridização In Situ , RNA Mensageiro/análise , Coelhos , Stents , Túnica Íntima/patologiaRESUMO
Repeated amphetamine (AMPH) administration results in behavioral sensitization. To investigate the participation of the opioid system in this phenomenon, we examined the effects of acute and repeated AMPH administration on mu-opioid receptor (MOR) mRNA levels in the nucleus accumbens (NAc) and striatum (STR) of rats, by quantitative non-radioactive in situ hybridization. Five injections of d-AMPH (1.5 mg kg-1, i.p., once every other day), resulted in a sensitization response profile and a significant down-regulation of MOR mRNA levels in the NAc shell, whereas no change was observed in MOR mRNA levels in the NAc core compared to the saline controls. Conversely, MOR mRNA levels were up-regulated in the rostral STR of AMPH-sensitized rats compared to saline controls. No changes in MOR mRNA levels were observed after acute AMPH treatment in any of the brain regions studied. These results suggest that the opioid system participates in the neurobiological underpinnings of behavioral sensitization and that opioid receptor (OR) expression in the STR and NAc shell and core is differentially modulated by repeated AMPH exposure.