RESUMEN
BACKGROUND: The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. METHODS: Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. RESULTS: Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. CONCLUSION: Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptor Notch1/biosíntesis , Receptor 1 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Receptor 3 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Receptor Notch1/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 3 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
Relato de caso de paciente de 38 anos, feminina, com lúpus eritematoso sistêmico (LES) que apresentou evento tromboembólico arterial agudo em membro inferior direito. A investigação evidenciou a presença de anticorpos antifosfolípides e vegetação asséptica em válvula mitral, endocardite de Libman-Sacks (eLS). São discutidas as possíveis causas de eventos tromboembólicos arteriais no LES, com ênfase nas recomendações atuais para diagnóstico e tratamento da eLS.
Case report of a 38-year-old female patient with systemic lupus erythematosus (SLE) who presented an acute arterial thromboembolic event in the right lower limb. Investigation showed the presence of antiphospholipid antibodies and sterile vegetation in the mitral valve, Libman-Sacks endocarditis (LSE). Possible causes of thromboembolic events in SLE are discussed, with emphasis on current recommendations for diagnosis and treatment of LSE.
Asunto(s)
Adulto , Femenino , Humanos , Anticuerpos Antifosfolípidos/inmunología , Endocarditis/etiología , Endocarditis/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Trombosis/etiología , Trombosis/inmunologíaRESUMEN
Case report of a 38-year-old female patient with systemic lupus erythematosus (SLE) who presented an acute arterial thromboembolic event in the right lower limb. Investigation showed the presence of antiphospholipid antibodies and sterile vegetation in the mitral valve, Libman-Sacks endocarditis (LSE). Possible causes of thromboembolic events in SLE are discussed, with emphasis on current recommendations for diagnosis and treatment of LSE.
