title: An animal model of preclinical diagnosis of pancreatic ductal adenocarcinomas.
abstract: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease, which is usually diagnosed in an advanced stage. Animal PDA models which reflect the human condition are clearly necessary to develop early diagnostic tools and explore new therapeutic approaches. We have established transgenic rats carrying a mutated H- or K-ras gene (Hras250 and Kras327) controlled by Cre/loxP activation. These animals develop PDA which are histopathologically similar to that in humans. We utilized this model to identify biomarkers to detect early PDA. We report here that serum levels of Erc/Mesothelin are significantly higher in rats bearing PDA than in controls. Importantly, the levels are significantly elevated in rats before grossly visible carcinomas develop. Even in rats with very small microscopic ductal carcinoma lesions, elevated serum Erc/Mesothelin can be detected. We believe this is the first report of a pancreas tumor animal model in which pre-symptomatic lesions can be diagnosed.
authors.affiliation: Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fukamachi
authors.forename: Hajime
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ohara
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iigo
authors.forename: David B
authors.initials: DB
authors.lastname: Alexander
authors.forename: Jiegou
authors.initials: J
authors.lastname: Xu
authors.forename: Ne
authors.initials: N
authors.lastname: Long
authors.forename: Misato
authors.initials: M
authors.lastname: Takigahira
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
authors.forename: Izumu
authors.initials: I
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D058851:GPI-Linked Proteins; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D000090204:Mesothelin; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C000715529:Msln protein, rat; D000090204:Mesothelin