RESUMO
UNLABELLED: Genetic alterations impacting the TGF-beta/Smad4 pathway are found in nearly all pancreatic adenocarcinomas, and recent reports have identified a relationship between DPC4/Smad4 expression and patient survival. In this study we use a clinically relevant animal model of pancreatic cancer to examine the impact of these genetic changes on the biology of pancreatic cancer. METHODS: Using high-density oligonucleotide DNA microarray technology, a comprehensive examination of the components of the TGF-beta/Smad4 pathway was performed on three human pancreatic adenocarcinoma cell lines. The in vitro and in vivo growth characteristics of these cell lines was then compared. Finally, using a clinically relevant orthotopic xenograft model of pancreatic cancer, primary tumor growth and metastases were measured for pancreatic tumors derived from each cell line. RESULTS: Examination of the TGF-beta/Smad4 pathway components identified that these three cell lines possess molecular profiles consistent with approximately 90% of pancreatic adenocarcinoma tumors in patients. A significant discrepancy between in vitro and in vivo growth characteristics of each cell line was identified. When tumors from each cell line were established in nu/nu mice, each cell line exhibited distinct metastatic profiles. Data from these studies is consistent, with clinical observations concerning DPC4/Smad4 and patient outcome. CONCLUSION: Using an orthotopic model of tumor growth and metastasis identifies distinct metastatic profiles associated with molecular alterations of the TGF-beta/Smad4 pathway and provides insight with regard to the biologic consequences of these changes.
Assuntos
Adenocarcinoma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Metástase Neoplásica , Neoplasias Pancreáticas/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transativadores/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína Smad4RESUMO
Intravascular ultrasound (IVUS) has an interesting history that parallels that of many of the advancements that have led to the endovascular era. The use of IVUS in conjunction with standard cross-sectional imaging and three-dimensional reconstructions offers a powerful tool in both the diagnosis and treatment of complex vascular pathology. The use of IVUS has increased over the years and is currently in the process of being incorporated into several modalities that will offer more in the way of real-time information in both the aortic arena and the treatment of increasingly complex peripheral vascular disease. Currently, we use IVUS as a powerful adjunct in combination with other modalities to increase our understanding of vessel architecture and assist in the management of complex vascular pathology.
Assuntos
Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Ultrassonografia de Intervenção , Implante de Prótese Vascular/história , Implante de Prótese Vascular/instrumentação , Procedimentos Endovasculares/história , Procedimentos Endovasculares/instrumentação , Desenho de Equipamento , História do Século XX , História do Século XXI , Humanos , Valor Preditivo dos Testes , Resultado do Tratamento , Ultrassonografia de Intervenção/história , Ultrassonografia de Intervenção/instrumentação , Dispositivos de Acesso VascularRESUMO
SUMMARY: We present a novel method for immediate umbilical reconstruction following surgical ablation of the umbilicus that is simple and reproducible with aesthetically satisfactory results.