Abstract: . . .  gene and protein expression profiles, comparative genomic hybridization, and analysis of mutations in key genes that contribute to the pathogenesis of the disease. (See also Section III, Scientific Toolkit.) 2. Develop experimental model systems. Also needed to pursue these priorities are in vitro, ex vivo, and animal models that faithfully recapitulate the complex biology of invasive human pancreatic cancer and its precursors. No existing animal model meets this criterion, and the dozens of human pancreatic cell lines that have been isolated remain underutilized for this purpose. Particular emphasis should be given to developing mouse and other models of normal and aberrant development, precursor lesions, signal transduction pathways, gene expression, carcinogenesis, and interactions between the tumor, stroma, and host. . . .
. . .  in appropriate animal models. In addition, non­ invasive methods for studying apoptosis in vivo are urgently needed. Clinical trials of agents targeting apoptosis should include markers of apoptosis as surrogate endpoints to better understand the mechanisms by which new antitumor agents either succeed or fail. Pancreatic cancer patients suffer more than most other cancer patients from cancer - related constitutional problems such as cachexia, weight loss, fatigue, and 16 Pancreatic Cancer : An Agenda for Action Page 27 depression. These symptoms and signs decrease a patient’s performance status and both quality and quantity of life, and are thought to adversely affect a patient’s ability to respond to therapies. The mechanisms associated with cancer -related sequelae are not well understood, but recent evidence indicates that tumor-derived factors such as zinc alpha2 glycoprotein and a proteolysis­ inducing factor may contribute to these symptoms. Clinical trials testing the actions eicosapentaenoic . . .
. . .  hybridization, and analysis of mutations in key genes that contribute to the pathogenesis of the disease. (See also Section III, Scientific Toolkit.) 2. Develop experimental model systems. Also needed to pursue these priorities are in vitro, ex vivo, and animal models that faithfully recapitulate the complex biology of invasive human pancreatic cancer and its precursors. No existing animal model meets this criterion, and the dozens of human pancreatic cell lines that have been isolated remain underutilized for this purpose. Particular emphasis should be given to developing mouse and other models of normal and aberrant development, precursor lesions, signal transduction pathways, gene expression, carcinogenesis, and interactions between the tumor, stroma, and host. . . .
--3000,3,500,2843,54276