RESUMO
Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Mastectomia Segmentar/normas , Oncologia/normas , Terapia Neoadjuvante/normas , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Consenso , Técnica Delphi , Feminino , Humanos , Mastectomia Segmentar/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
Female sexual behavior is a complex process regulated by multiple brain circuits and influenced by sex steroid hormones acting in the brain. Several regions in the hypothalamus have been implicated in the regulation of female sexual behavior although a complete circuitry involved in female sexual behavior is not understood. Fez family zinc finger 1 (Fezf1) gene is a brain specific gene that has been mostly studied in the context of olfactory development, although in a recent study, FEZF1 has been identified as one of the genes responsible for the development of Kallman syndrome. In the present study, we utilized shRNA approach to downregulate Fezf1 in the ventromedial nucleus of the hypothalamus (VMN) with the aim to explore the role of this gene. Adult female mice were stereotaxically injected with lentiviral vectors encoding shRNA against Fezf1 gene. Mice injected with shRNA against Fezf1 had significantly reduced female sexual behavior, presumably due to the downregulation of estrogen receptor alpha (ERα), as the number of ERα-immunoreactive cells in the VMN of Fezf1 mice was significantly lower in comparison to controls. However, no effect on body weight or physical activity was observed in mice with downregulated Fezf1, suggesting that the role of Fezf1 in the VMN is limited to the regulation of sexual behavior. SIGNIFICANCE STATEMENT: Fezf1 gene has been identified in the present study as a regulator of female sexual behavior in mice. Regulation of the female sexual behavior could be through the regulation of estrogen receptor alpha expression in the ventromedial nucleus of the hypothalamus, as the expression of this receptor was reduced in mice with downregulated Fezf1. As expression of Fezf1 is very specific in the brain, this gene could present a potential target for the development of novel drugs regulating hypoactive sexual desire disorder in women, if similar function of FEZF1 will be confirmed in humans.
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Proteínas de Ligação a DNA/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Comportamento Sexual Animal/fisiologia , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Receptor alfa de Estrogênio/genética , Feminino , Camundongos , Proteínas do Tecido Nervoso/genética , RNA Interferente Pequeno , Proteínas RepressorasRESUMO
OBJECTIVES: Biofilm-associated implant infections represent a serious public health problem. Covalent immobilization of antimicrobial agents on titanium (Ti), thereby inhibiting biofilm formation of microbial pathogens, is a solution to this problem. METHODS: Vancomycin (VAN) and caspofungin (CAS) were covalently bound on Ti substrates using an improved processing technique adapted to large-scale coating of implants. Resistance of the VAN-coated Ti (VAN-Ti) and CAS-coated Ti (CAS-Ti) substrates against in vitro biofilm formation of the bacterium Staphylococcus aureus and the fungal pathogen Candida albicans was determined by plate counting and visualized by confocal laser scanning microscopy. The efficacy of the coated Ti substrates was also tested in vivo using an adapted biomaterial-associated murine infection model in which control-Ti, VAN-Ti or CAS-Ti substrates were implanted subcutaneously and subsequently challenged with the respective pathogens. The osseointegration potential of VAN-Ti and CAS-Ti was examined in vitro using human bone marrow-derived stromal cells, and for VAN-Ti also in a rat osseointegration model. RESULTS: In vitro biofilm formation of S. aureus and C. albicans on VAN-Ti and CAS-Ti substrates, respectively, was significantly reduced compared with biofilm formation on control-Ti. In vivo, we observed over 99.9% reduction in biofilm formation of S. aureus on VAN-Ti substrates and 89% reduction in biofilm formation of C. albicans on CAS-Ti substrates, compared with control-Ti substrates. The coated substrates supported osseointegration in vitro and in vivo. CONCLUSIONS: These data demonstrate the clinical potential of covalently bound VAN and CAS on Ti to reduce microbial biofilm formation without jeopardizing osseointegration.
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Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Titânio/farmacologia , Animais , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida albicans/fisiologia , Caspofungina , Linhagem Celular , Equinocandinas/farmacologia , Feminino , Humanos , Lipopeptídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Osseointegração , Próteses e Implantes/microbiologia , Staphylococcus aureus/fisiologia , Vancomicina/farmacologiaRESUMO
The presence of steroidogenic enzymes in the brain suggests de novo synthesis of steroid hormones in the brain. The current study was designed to determine the developmental profiles of cytochrome p450 aromatase (cyp19), 17ß-hydroxysteroid dehydrogenase (17ß-HSD), 5α-reductase type I and 3α-hydroxysteroid dehydrogenase (3α-HSD) mRNA expression levels in the fetal mouse brain and potential influence of peripheral steroids, and the steroidogenic factor 1 (SF-1) gene on their expression. Brains were collected from WT and SF-1 knockout male and female fetuses at embryonic (E) days E12, E14, E16, and E18. Quantitative PCR analyses revealed age related increases in the expression levels of 17ß-HSD and 5α-reductase. Differences between genotypes in the expression levels of 17ß-HSD and 5α-reductase were detected on E14, with reduced levels of expression in SF-1 KO males and females for 17ß-HSD and only between females for 5α-reductase. Expression of 3α-HSD mRNA did not differ significantly between sexes, age groups or genotypes with the exception of SF-1 KO males, which had an unexplained increase in mRNA for this enzyme on day E18. Expression of cyp19 was at the limit of detection and could not be analyzed effectively. There were no sex differences and, with the exception of small difference on E14 for 17ß-HSD and 5α-reductase, no differences between genotypes. The results suggest that gonadal steroids do not influence the production of neurosteroids in the fetal brain, nor does SF-1 play a major role in the regulation of steroidogenic enzyme expression in the brain.
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17-Hidroxiesteroide Desidrogenases/genética , 3-alfa-Hidroxiesteroide Desidrogenase (B-Específica)/genética , Aromatase/genética , Encéfalo/metabolismo , Colestenona 5 alfa-Redutase/genética , Fator Esteroidogênico 1/genética , 17-Hidroxiesteroide Desidrogenases/metabolismo , 3-alfa-Hidroxiesteroide Desidrogenase (B-Específica)/metabolismo , Animais , Aromatase/metabolismo , Colestenona 5 alfa-Redutase/metabolismo , Feminino , Masculino , Camundongos , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Caracteres Sexuais , Fator Esteroidogênico 1/metabolismoRESUMO
The European Breast Cancer Council (EBCC) traditionally identifies controversies or major deficiencies in the management of patients with breast cancer and selects a multidisciplinary expert team to collaborate in setting crucial principles and recommendations to improve breast cancer care. The 2024 EBCC manifesto focuses on disparities in the care of patients with metastatic breast cancer. There are several reasons for existing disparities both between and within countries. Our recommendations aim to address the stigma of metastatic disease, which has led to significant disparities in access to innovative care regardless of the gross national income of a country. These recommendations are for different stakeholders to promote the care of patients with metastatic breast cancer across Europe and worldwide.
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Neoplasias da Mama , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Europa (Continente) , Feminino , Metástase NeoplásicaRESUMO
INTRODUCTION: Quality care in breast cancer is higher if patients are treated in a Breast Center with a dedicated and specialized multidisciplinary team. Quality control is an essential activity to ensure quality care, which has to be based on the monitoring of specific quality indicators. Eusoma has proceeded with the up-dating of the 2017 Quality indicators for non-metastatic breast cancer based on the new diagnostic, locoregional and systemic treatment modalities. METHODS: To proceed with the updating, EUSOMA setup a multidisciplinary working group of BC experts and patients' representatives. It is a comprehensive set of QIs for early breast cancer care, which are classified as mandatory, recommended, or observational. For the first time patient reported outcomes (PROMs) have been included. As used in the 2017 EUSOMA QIs, evidence levels were based on the short version of the US Agency for Healthcare Research and Quality. RESULTS: This is a set of quality indicators representative for the different steps of the patient pathway in non-metastatic setting, which allow Breast Centres to monitor their performance with referring standards, i.e minimum standard and target. CONCLUSIONS: Monitoring these Quality Indicators, within the Eusoma datacentre will allow to have a state of the art picture at European Breast Centres level and the development of challenging research projects.
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Neoplasias da Mama , Indicadores de Qualidade em Assistência à Saúde , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Qualidade da Assistência à SaúdeRESUMO
The European Society for Radiotherapy and Oncology (ESTRO) has advocated the establishment of guidelines to optimise precision radiotherapy (RT) in conjunction with contemporary therapeutics for cancer care. Quality assurance in RT (QART) plays a pivotal role in influencing treatment outcomes. Clinical trials incorporating QART protocols have demonstrated improved survival rates with minimal associated toxicity. Nonetheless, in routine clinical practice, there can be variability in the indications for RT, dosage, fractionation, and treatment planning, leading to uncertainty. In pivotal trials reporting outcomes of systemic therapy for breast cancer, there is limited information available regarding RT, and the potential interaction between modern systemic therapy and RT remains largely uncharted. This article is grounded in a consensus recommendation endorsed by ESTRO, formulated by international breast cancer experts. The consensus was reached through a modified Delphi process and was presented at an international meeting convened in Florence, Italy, in June 2023. These recommendations are regarded as both optimal and essential standards, with the latter aiming to define the minimum requirements. A template for a case report form (CRF) has been devised, which can be utilised by all clinical breast cancer trials involving RT. Optimal requirements include adherence to predefined RT planning protocols and centralised QART. Essential requirements aim to reduce variations and deviations from the guidelines in RT, even when RT is not the primary focus of the trial. These recommendations underscore the significance of implementing these practices in both clinical trials and daily clinical routines to generate high-quality data.
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Neoplasias da Mama , Ensaios Clínicos como Assunto , Consenso , Humanos , Neoplasias da Mama/radioterapia , Feminino , Ensaios Clínicos como Assunto/normas , Europa (Continente) , Radioterapia (Especialidade)/normas , Sociedades Médicas , Garantia da Qualidade dos Cuidados de Saúde/normasRESUMO
PURPOSE: We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy. PATIENTS AND METHODS: POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months. RESULTS: Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5). CONCLUSION: In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.
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Neoplasias da Mama , Preservação da Fertilidade , Técnicas de Reprodução Assistida , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Adulto , Gravidez , Preservação da Fertilidade/métodos , Estudos Prospectivos , Quimioterapia Adjuvante/efeitos adversos , Indução da Ovulação/métodos , Indução da Ovulação/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Pessoa de Meia-Idade , CriopreservaçãoRESUMO
PURPOSE: The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2, high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment. METHODS: Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains. Scores were compared between treatment groups using mixed model for repeated measures. Two-sided P values <.05 were statistically significant for the primary end point. All secondary end points were descriptive. RESULTS: One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: -1.3 [95% CI, -2.4 to -0.2]; P = .022; ACT: -1.3 [95% CI, -2.3 to -0.2]; P = .017) and 12 months (NACT: -1.6 [95% CI, -2.8 to -0.3]; P = .017; ACT: -1.3 [95% CI, -2.4 to -0.2]; P = .025). There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]). During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status. CONCLUSION: Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients.
Assuntos
Neoplasias da Mama , Ftalazinas , Piperazinas , Qualidade de Vida , Receptor ErbB-2 , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Fadiga/induzido quimicamente , Mutação , Náusea , Medidas de Resultados Relatados pelo Paciente , VômitoRESUMO
After a diagnosis of unilateral breast cancer, increasing numbers of patients are requesting contralateral prophylactic mastectomy (CPM), the surgical removal of the healthy breast after diagnosis of unilateral breast cancer. It is important for the community of breast cancer specialists to provide meaningful guidance to women considering CPM. This manifesto discusses the issues and challenges of CPM and provides recommendations to improve oncological, surgical, physical and psychological outcomes for women presenting with unilateral breast cancer: (1) Communicate best available risks in manageable timeframes to prioritise actions; better risk stratification and implementation of risk-assessment tools combining family history, genetic and genomic information, and treatment and prognosis of the first breast cancer are required; (2) Reserve CPM for specific situations; in women not at high risk of contralateral breast cancer (CBC), ipsilateral breast-conserving surgery is the recommended option; (3) Encourage patients at low or intermediate risk of CBC to delay decisions on CPM until treatment for the primary cancer is complete, to focus on treating the existing disease first; (4) Provide patients with personalised information about the risk:benefit balance of CPM in manageable timeframes; (5) Ensure patients have an informed understanding of the competing risks for CBC and that there is a realistic plan for the patient; (6) Ensure patients understand the short- and long-term physical effects of CPM; (7) In patients considering CPM, offer psychological and surgical counselling before surgery; anxiety alone is not an indication for CPM; (8) Eliminate inequality between countries in reimbursement strategies; CPM should be reimbursed if it is considered a reasonable option resulting from multidisciplinary tumour board assessment; (9) Treat breast cancer patients at specialist breast units providing the entire patient-centred pathway.
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Neoplasias da Mama , Mastectomia Profilática , Neoplasias Unilaterais da Mama , Humanos , Feminino , Mastectomia/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Mastectomia Profilática/psicologia , Neoplasias Unilaterais da Mama/psicologia , Neoplasias Unilaterais da Mama/cirurgia , Mama/patologiaRESUMO
Female receptivity including the immobile hormone-dependent lordosis posture is essential for successful reproduction in rodents. It is well documented that lordosis is organized during the perinatal period when the actions of androgens decrease the males' ability to display this behavior in adulthood. Conversely the absence of androgens, and the presence of low levels of prepubertal estrogens, preserve circuitry that regulates this behavior in females. The current study set out to determine whether sex chromosomal genes are involved in the differentiation of this behavior. An agonadal mouse model was used to test this hypothesis. The SF-1 gene (Nr5a1) is required for development of gonads and adrenal glands, and knockout mice are consequently not exposed to endogenous gonadal steroids. Thus contributions of sex chromosome genes can be disassociated from the actions of estrogens. Use of this model reveals a direct genetic contribution from sex chromosomes in the display of lordosis and other female-typical sexual behavior patterns. It is likely that the concentrations of gonadal steroids present during normal male development modify the actions of sex chromosome genes on the potential to display female sexual behavior.
Assuntos
Cromossomos Sexuais/genética , Diferenciação Sexual/genética , Comportamento Sexual Animal/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Postura/fisiologia , Receptores de Progesterona/metabolismo , Roedores/genética , Roedores/metabolismo , Roedores/fisiologia , Caracteres Sexuais , Cromossomos Sexuais/fisiologia , Fator Esteroidogênico 1/genéticaRESUMO
Significant progress has been achieved in human health in the European Union in recent years. New medicines, vaccines, and treatments have been developed to tackle some of the leading causes of disease and life-threatening illnesses. It is clear that investment in research and development (R&D) for innovative medicines and treatments is essential for making progress in preventing and treating diseases. Ahead of the legislative process, which should begin by the end of 2022, discussions focus on how Europe can best promote the huge potential benefits of new science and technology within the regulatory framework. The challenges in European healthcare were spelled out by the panellists at the roundtable organised by European Alliance for Personalised Medicine (EAPM). Outcomes from panellists' discussions have been summarized and re-arranged in this paper under five headings: innovation, unmet medical need, access, security of supply, adapting to progress, and efficiency. Some of the conclusions that emerged from the panel are a call for a better overall holistic vision of the future of pharmaceuticals and health in Europe and a collaborative effort among all stakeholders, seeing the delivery of medicines as part of a broader picture of healthcare.
RESUMO
PURPOSE: We aimed to assess patients' and physicians' perspectives on wider implementation of telemedicine in radiation oncology practice, disrupted by the novel coronavirus disease 2019 (COVID-19). METHODS: Quantitative questionnaires were prepared and distributed between May 27 and June 11, 2020. A 29-question survey targeting patients with cancer was distributed electronically via cancer support organizations. Cross-sectional data from a selected weekday at a radiation oncology department were also analyzed. In addition, a 25-question survey was distributed to 168 physicians employed by a comprehensive cancer center. RESULTS: In total, we have analyzed 468 patients' and 101 physicians' responses. Among responding patients, 310 were undergoing active treatment and 158 were in follow-up care. Both patients and physicians reported no experiences with video consultations during the COVID-19 pandemic, but 15% of patients stated that they missed telemedicine services that would include a video call. Overall, 30.6% of patients expressed interest in more frequent usage of telemedicine and 23.3% would start using it. Sixty-seven percent of radiation oncologists expressed interest in more frequent usage of telemedicine, and 14% would use it similarly as in the past. For patients treated with radiation therapy (RT), 59.9% and 63.4% of the responding patients acknowledged that video consultations would be an important addition to medical care during RT course or after the completion of RT, respectively. Comparably, 61.1% and 63.9% of radiation oncologists believed video consultations would be useful or extremely useful for patients undergoing RT or for patients in the follow-up setting, respectively. CONCLUSIONS: The post-COVID-19 era represents a unique chance to improve and guarantee continuity of cancer care via telemedicine solutions, when appropriate.
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Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Radioterapia (Especialidade)/métodos , Telemedicina , Adulto , Idoso , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos/psicologia , Inquéritos e QuestionáriosRESUMO
Biofilms, especially those formed by Staphylococcus aureus, play a key role in the development of orthopedic implant infections. Eradication of these infections is challenging due to the elevated tolerance of biofilm cells against antimicrobial agents. In this study, we developed an antibiofilm coating consisting of 5-(4-bromophenyl)-N-cyclopentyl-1-octyl-1H-imidazol-2-amine, designated as LC0024, covalently bound to a titanium implant surface (LC0024-Ti). We showed in vitro that the LC0024-Ti surface reduces biofilm formation of S. aureus in a specific manner without reducing the planktonic cells above the biofilm, as evaluated by plate counting and fluorescence microscopy. The advantage of compounds that only inhibit biofilm formation without affecting the viability of the planktonic cells, is that reduced development of bacterial resistance is expected. To determine the antibiofilm activity of LC0024-Ti surfaces in vivo, a biomaterial-associated murine infection model was used. The results indicated a significant reduction in S. aureus biofilm formation (up to 96%) on the LC0024-Ti substrates compared to pristine titanium controls. Additionally, we found that the LC0024-Ti substrates did not affect the attachment and proliferation of human cells involved in osseointegration and bone repair. In summary, our results emphasize the clinical potential of covalent coatings of LC0024 on titanium implant surfaces to reduce the risk of orthopedic implant infections. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1908-1919, 2019.
Assuntos
Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis , Imidazóis , Teste de Materiais , Staphylococcus aureus/fisiologia , Titânio , Animais , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Camundongos , Titânio/química , Titânio/farmacologiaRESUMO
The 3rd International Consensus Conference for Breast Cancer in Young Women (BCY3) took place in November 2016, in Lugano, Switzerland organized by the European School of Oncology (ESO) and the European Society of Medical Oncologists (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY2 with incorporation of new evidence to inform the guidelines, and areas of research priorities were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).
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Neoplasias da Mama/terapia , Consenso , Oncologia/normas , Guias de Prática Clínica como Assunto/normas , Adulto , Neoplasias da Mama/prevenção & controle , Gerenciamento Clínico , Feminino , Humanos , Sociedades Médicas/normas , Suíça , Adulto JovemRESUMO
Steroidogenic factor 1 (SF-1), officially designated NR5A1, is essential for gonadal and adrenal development and for the normal structure of the ventromedial hypothalamus (VMH), as demonstrated by SF-1 knockout mice (SF-1 KO), but much less is known about the possible effects of haploinsufficiency of the SF-1 gene. In the present study, maternal behavior in SF-1 KO heterozygous mice was evaluated. Behavioral tests revealed that SF-1 KO heterozygous females have impaired maternal behavior. In comparison to wild-type (WT) females, SF-1 KO heterozygous females retrieved significantly fewer pups into their nests, latency to retrieve and crouch over the pups was longer, and their nests were lower quality. As suggested by previous studies full dosage of SF-1 gene is needed for appropriate stress response and expression of brain-derived neurotrophic factor (BDNF) in the brain, and this might present a mechanism through which maternal behavior in SF-1 KO heterozygous females is impaired.