ABSTRACT
Triple-negative breast cancer (TNBC) comprises 15-20% of all breast cancers (BC). Lacking targeted therapy options, TNBC becomes the focal point of clinical investigations aiming not only to identify drugs with enhanced response potential but also to uncover new immunological and/or metabolic pathways conducive to more effective treatments. Currently, neoadjuvant treatment for TNBC relies on standard chemotherapy in conjunction with immunotherapy, given the improved response observed with this drug combination. This review delves into the latest therapeutic updates in TNBC treatment and explores potential advancements shaping the future landscape of this disease in the neoadjuvant setting.
Subject(s)
Neoadjuvant Therapy , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Immunotherapy , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
BACKGROUND: Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain. METHODS: We used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 10(2)), medium (3 × 10(3)), and high (3 × 10(4)) parasite loads were generated by infecting C57BL/6 mice with "Y"-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey's multiple comparison post-test, Kruskal-Wallis test with Dunn's multiple comparison, χ2 test and Spearman correlation. RESULTS: High parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines. CONCLUSIONS: These experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.
Subject(s)
Chagas Disease/pathology , Inflammation/pathology , Intestines/pathology , Parasite Load , Trypanosoma cruzi/isolation & purification , Animals , Chagas Disease/parasitology , Cytokines/analysis , Disease Models, Animal , Histocytochemistry , Immunohistochemistry , Intestines/parasitology , Mice, Inbred C57BL , Microscopy , Parasitemia/parasitology , Survival Analysis , Time FactorsABSTRACT
O implante de cardiodesfibriladores automáticos surgiu na década de 1980 como tratamentoalternativo na prevenção de arritmias graves em pacientes sobreviventes de fibrilação ventricular ou taquicardiaventricular sintomática. Os resultados iniciais mostraram resultados favoráveis à prevenção de morte súbita eredução de mortalidade geral com o uso desses dispositivos. Diante disso, a comprovação dessas evidências porestudos randomizados tornou-se de suma importância para indicação dessa prótese. A revisão dos resultadosdesses estudos demonstrou que o implante de cardiodesfibrilador automático éprimeira opção na terapêuticade pacientes com taquicardia ventricular sustentada ou fibrilação ventricular com comprometimentohemodinâmico, sendo também superior ao tratamento farmacológico em pacientes com taquicardia ventricularsustentada sintomática ou após ressuscitação de parada cardiorrespiratória. Nos casos de doença arterialcoronária, disfunção ventricular esquerda e presença de potenciais tardios ao eletrocardiograma, não háevidências em favor do implante desse dispositivo. O implante profilático de cardiodesfibrilador implantável empacientes de alto risco com infarto agudo do miocárdio recente não reduz a mortalidade geral. Esse dispositivonão representa benefícios para a sobrevivência nos casos de cardiomiopatia dilatada idiopática. A terapia comcardiodesfibrilador implantável combinada à terapia de ressincronização cardíaca melhora a qualidade devida, a classe funcional e a capacidade física na insuficiência cardíaca moderada a grave. Esse dispositivo estáassociado a redução equivalente da mortalidade em idosos e em indivíduos mais jovens, sem comprometimentoda qualidade de vida nos idosos, excluindo-se pacientes com comorbidades graves. O objetivo deste artigo érevisar os principais estudos clínicos em cardiodesfibrilador implantável, avaliando aspectos essenciais paraindicação dessa terapêutica.
The implantation of implantable cardioverter-defibrillators emerged in the 1980s as an alternativetreatment in the prevention of serious arrhythmias in survivors of ventricular fibrillation or symptomatic ventriculartachycardia. Initial results showed favorable for prevention of sudden death and overall mortality reduction withimplantable cardioverter-defibrillator results. Therefore, the evidence of such evidence by randomized trials hasbecome of paramount importance for implantable cardioverter-defibrillator indication. A review of the results of hese studies demonstrated that implantable cardioverter-defibrillator implantation is first choice in the treatmentof patients with sustained ventricular tachycardia or ventricular fibrillation with hemodynamic compromise,being also superior to medical therapy in patients with symptomatic sustained ventricular tachycardia or afterresuscitation from cardiac arrest. In cases of coronary artery disease, left ventricular dysfunction and presenceof late potentials on electrocardiogram, there is no evidence in favor of implantable cardioverter-defibrillatorimplantation. Prophylactic implantable cardioverter-defibrillator implantation in high-risk patients with recentacute myocardial infarction does not reduce overall mortality. The implantable cardioverter-defibrillator doesnot represent benefits for survival in cases of idiopathic dilated cardiomyopathy. Combination therapy withimplantable cardioverter-defibrillator and cardiac resynchronization therapy improves quality of life, functionalclass and exercise capacity in moderate to severe heart failure. The implantable cardioverter-defibrillator isassociated with an equivalent reduction of mortality in elderly and younger subjects without impairment ofquality of life in elderly patients, excluding patients with severe comorbidities.
