RESUMO
PURPOSE: Little is known concerning the onset, duration, and magnitude of direct therapeutic effects of anti-vascular endothelial growth factor (VEGF) therapies. Such knowledge would help guide the rational development of targeted therapeutics from bench to bedside and optimize use of imaging technologies that quantify tumor function in early-phase clinical trials. EXPERIMENTAL DESIGN: Preclinical studies were done using ex vivo microcomputed tomography and in vivo ultrasound imaging to characterize tumor vasculature in a human HM-7 colorectal xenograft model treated with the anti-VEGF antibody G6-31. Clinical evaluation was by quantitative magnetic resonance imaging in 10 patients with metastatic colorectal cancer treated with bevacizumab. RESULTS: Microcomputed tomography experiments showed reduction in perfused vessels within 24 to 48 h of G6-31 drug administration (P Assuntos
Inibidores da Angiogênese/uso terapêutico
, Anticorpos Monoclonais/uso terapêutico
, Neoplasias Colorretais/irrigação sanguínea
, Neoplasias Colorretais/tratamento farmacológico
, Diagnóstico por Imagem
, Fator A de Crescimento do Endotélio Vascular/imunologia
, Adolescente
, Animais
, Anticorpos Monoclonais/farmacologia
, Anticorpos Monoclonais Humanizados
, Bevacizumab
, Linhagem Celular Tumoral
, Sistemas de Liberação de Medicamentos
, Feminino
, Humanos
, Camundongos
, Camundongos Nus
, Neovascularização Patológica/tratamento farmacológico
, Ensaios Antitumorais Modelo de Xenoenxerto