ABSTRACT
PREDICT is a tool designed to estimate the benefits of adjuvant therapy and the overall survival of women with early breast cancer. The model uses clinical, histological, and immunohistochemical variables. This study aimed to evaluate the model's performance in a Brazilian population. We assessed the discrimination and calibration of the PREDICT model to estimate overall survival (OS) in five and ten years of follow-up in a cohort of 873 women with early breast cancer diagnosed from January 2001 to December 2016. A total of 743 patients had estrogen receptor (ER)-positive and 130 had ER-negative tumors. The area under the receiver operating characteristic (ROC) curve (AUC) for discrimination was 0.72 (95%CI: 0.66-0.78) at five years and 0.67 (95%CI: 0.61-0.72) at ten years for women with ER-positive tumors. The AUC was 0.72 (95%CI: 0.62-0.81) at five years and 0.67 (95%CI: 0.54-0.77) at ten years for women with ER-negative tumors. The predicted survival in ER-positive tumors was 91.0% (95%CI: 90.2-91.6%) at five years and 79.3% (95%CI: 77.7-81.0%) at ten years, and the observed survival 90.7% (95%CI: 88.6-92.9%) and 77.2% (95%CI: 73.4-81.4%), respectively. The predicted survival in ER-negative tumors was 84.5% (95%CI: 82.5-86.6%) at five years and 75.0% (95%CI: 71.6-78.5%) at ten years, and the observed survival 76.3% (95%CI: 69.1-84.3%) and 67.9% (95%CI: 58.6-78.6%), respectively. In conclusion, PREDICT was accurate to estimate OS in women with ER-positive tumors and overestimated the OS in women with ER-negative tumors.
ABSTRACT
Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.
Subject(s)
Humans , Female , Breast Neoplasms , Neutrophils , Prognosis , Lymphocytes , Retrospective Studies , Neoplasm Recurrence, Local , Obesity/complicationsABSTRACT
Abstract The current COVID-19 pandemic caused by the novel coronavirus (SARS-CoV2) poses a threat to global health owing to its high rate of spread and severe forms of respiratory infection. The lack of vaccines and antivirals prevents clinical strategies against the disease, creating an emerging need for the development of safe and effective treatments. Strategies for vaccine development include complete vaccines against viruses, subunits, and nucleic acids, but are still in their early stages. Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). However, due to the pandemic state, priority is given to marketed drugs. These include chloroquine (CQ), hydroxychloroquine (HCQ), nitazoxanide, remdesivir, Lopinavir/ritonavir (LPV / r), in addition to treatment with convalescent plasma. But, therapeutic specific effects against SARS-CoV2 have not yet been verified. Most of the information obtained about treatment is based on preliminary and limited studies. We conclude that, at this time of emergency, the search for new therapies is more urgent due to the need to save lives. Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.
Resumo A pandemia de COVID-19 causada pelo novo Coronavírus (SARS-CoV2) representa uma ameaça à saúde global devido à alta taxa de disseminação e formas graves de infecção respiratória. A falta de vacinas e antivirais específicos dificultam as estratégias clínicas de controle da doença, criando a necessidade urgente do desenvolvimento de tratamentos seguros e eficazes. Com relação as estratégias para o desenvolvimento de vacinas, incluem-se: aquelas com o vírus completo, subunidades e ácidos nucléicos, mas estas ainda estão em estágios iniciais. Já sobre os estudos realizados até o momento buscando novos alvos terapêuticos contra o SARS-CoV2, destacam a glicoproteína S; Mpro (principal protease ou protease tipo 3C) e um membro da família transmembrana serina protease II (TMPRSS2). No entanto, devido ao estado pandêmico, tem sido dada prioridade aos medicamentos comercializados. Estes incluem a cloroquina (CQ); hidroxicloroquina (HCQ); nitazoxanida; remdesivir; Lopinavir / ritonavir (LPV/r); além do tratamento com plasma de pacientes curados. Porém, ainda não há uma estratégia terapêutica contra o SARS-CoV2 totalmente eficaz, e a maioria das informações obtidas sobre o tratamento é baseada em estudos preliminares e limitados. Concluímos então que, neste momento de emergência, a busca por novas terapias é algo urgente devido à necessidade de salvar vidas. Assim finalizamos sugerindo como alvos interessantes para futuras pesquisas específicas: a glicoproteína S, Mpro e o TMPRSS2.
Subject(s)
Humans , Pneumonia, Viral , Viral Vaccines , Coronavirus Infections/prevention & control , Coronavirus Infections/drug therapy , Pandemics , Betacoronavirus , Drug Development , COVID-19 Vaccines , SARS-CoV-2 , COVID-19ABSTRACT
Abstract The current COVID-19 pandemic caused by the novel coronavirus (SARS-CoV2) poses a threat to global health owing to its high rate of spread and severe forms of respiratory infection. The lack of vaccines and antivirals prevents clinical strategies against the disease, creating an emerging need for the development of safe and effective treatments. Strategies for vaccine development include complete vaccines against viruses, subunits, and nucleic acids, but are still in their early stages. Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). However, due to the pandemic state, priority is given to marketed drugs. These include chloroquine (CQ), hydroxychloroquine (HCQ), nitazoxanide, remdesivir, Lopinavir/ritonavir (LPV / r), in addition to treatment with convalescent plasma. But, therapeutic specific effects against SARS-CoV2 have not yet been verified. Most of the information obtained about treatment is based on preliminary and limited studies. We conclude that, at this time of emergency, the search for new therapies is more urgent due to the need to save lives. Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.
Resumo A pandemia de COVID-19 causada pelo novo Coronavírus (SARS-CoV2) representa uma ameaça à saúde global devido à alta taxa de disseminação e formas graves de infecção respiratória. A falta de vacinas e antivirais específicos dificultam as estratégias clínicas de controle da doença, criando a necessidade urgente do desenvolvimento de tratamentos seguros e eficazes. Com relação as estratégias para o desenvolvimento de vacinas, incluem-se: aquelas com o vírus completo, subunidades e ácidos nucléicos, mas estas ainda estão em estágios iniciais. Já sobre os estudos realizados até o momento buscando novos alvos terapêuticos contra o SARS-CoV2, destacam a glicoproteína S; Mpro (principal protease ou protease tipo 3C) e um membro da família transmembrana serina protease II (TMPRSS2). No entanto, devido ao estado pandêmico, tem sido dada prioridade aos medicamentos comercializados. Estes incluem a cloroquina (CQ); hidroxicloroquina (HCQ); nitazoxanida; remdesivir; Lopinavir / ritonavir (LPV/r); além do tratamento com plasma de pacientes curados. Porém, ainda não há uma estratégia terapêutica contra o SARS-CoV2 totalmente eficaz, e a maioria das informações obtidas sobre o tratamento é baseada em estudos preliminares e limitados. Concluímos então que, neste momento de emergência, a busca por novas terapias é algo urgente devido à necessidade de salvar vidas. Assim finalizamos sugerindo como alvos interessantes para futuras pesquisas específicas: a glicoproteína S, Mpro e o TMPRSS2.
ABSTRACT
The present study aimed to compare the morphometric measurements of Mangalarga Marchador horses of batida and picada marcha. Twenty-two linear and eight angular measurements of 222 males (130 of batida marcha and 92 of picada marcha) and 266 females (168 of batida marcha and 98 picada marcha) were compared in a completely randomized design, consisting of two treatments: horses of batida and picada marcha. The results were submitted to analysis of variance and means were compared by Fisher test (P<0.05). It was concluded that most of the measures of Mangalarga Marchador horses of batida and picada marcha have similar values, however, there are differences between some angles of members...
Subject(s)
Animals , Male , Female , Biomechanical Phenomena , Biometry , Horses/anatomy & histology , Gait/physiology , Range of Motion, Articular/physiology , Movement/physiologyABSTRACT
Patients with advanced cervical cancer have deficient natural killer (NK) cell activity, usually as a consequence of tumor invasion, which results in tumor NK cell sequestration. The reason for the occurrence of such alterations in patients under chemotherapy is unknown. We evaluated the activity and number of NK cells and T cell subpopulations in ten patients before and three weeks after neoadjuvant chemotherapy (CT). The schedule used was cis-platinum (100 Mg/M2 per cycle) and bleomycin (15 mg/cycle), repeated every 28 days. Although there were similar levels of NK cells before and after CT in both groups, we observed greater cytotoxicity of peripheral blood lymphocytes and increased levels of CD4+ and CD8+ T cells (P<0.01) in five patients who presented a good clinical response when compared to the group with a poor response. IL- 12, known to increase NK cell activity when added to peripheral blood lymphocyte cultures, markedly increased lytic activity before and after CT only in the group with a good clinical response. These results suggest that NK cells from the poorly responding patient group express less lytic activity per NK cell and are insensitive to IL- 12 stimulation, probably as a result of reduced IL-12 receptor expression or a defective intracellular transduction mechanism. The present findings may be useful as a prognostic factor in clinical practice and also provide support for human clinical trials of IL- 12 and neoadjuvant CT for the treatment of malignant cervical tumors.
Subject(s)
Humans , Uterine Cervical Dysplasia/drug therapy , Interleukin-12/physiology , Killer Cells, Natural/physiology , Uterine Cervical Dysplasia/complications , Chemotherapy, Adjuvant/adverse effects , Flow Cytometry , Killer Cells, Natural/drug effectsABSTRACT
El objetivo primordial del presente trabajo es dar una visión general de las características que presenta el hierro en el cuerpo humano y hacer una recopilación de los métodos más recientemente propuestos para su determinación. Esta visión pretende ser una clasificación general de metodologías, ilustradas con ejemplos de casos propuestos por los investigadores actuales para que pueda servir de punto de arranque en un mayor estudio; algo que, creemos, es de la mayor importancia. Se hará así un exhautivo recorrido por lo publicado desde enero de 1983 hasta enero de 1990