An animal model of preclinical diagnosis of pancreatic ductal adenocarcinomas

被引:17
作者
Fukamachi, Katsumi [2 ]
Tanaka, Hajime [3 ]
Hagiwara, Yoshiaki [4 ,5 ]
Ohara, Hirotaka [3 ]
Joh, Takashi [3 ]
Iigo, Masaaki [2 ]
Alexander, David B. [2 ]
Xu, Jiegou [2 ]
Long, Ne [2 ]
Takigahira, Misato [6 ,7 ]
Yanagihara, Kazuyoshi [6 ,8 ]
Hino, Okio [5 ]
Saito, Izumu [9 ]
Tsuda, Hiroyuki [1 ,2 ]
机构
[1] Nagoya City Univ, Grad Sch Med Sci, Nanotoxicol Project, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[2] Nagoya City Univ, Grad Sch Med Sci, Dept Mol Toxicol, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[3] Nagoya City Univ, Grad Sch Med Sci, Dept Gastroenterol & Metab, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[4] Immunobiol Labs, Takasaki, Gunma 3700831, Japan
[5] Juntendo Univ, Sch Med, Dept Pathol & Oncol, Tokyo 1138421, Japan
[6] Natl Canc Ctr, Res Inst, Cent Anim Lab, Chuo Ku, Tokyo 1040045, Japan
[7] Natl Canc Ctr, Gastrointestinal Sect, Chuo Ku, Tokyo 1040045, Japan
[8] Yasuda Womens Univ, Dept Life Sci, Lab Hlth Sci, Asaminami Ku, Hiroshima 7310153, Japan
[9] Univ Tokyo, Inst Med Sci, Genet Mol Lab, Minato Ku, Tokyo 1088639, Japan
基金
日本学术振兴会;
关键词
Pancreas cancer; Serum marker; Erc; Mesothelin; Animal model; LINKED-IMMUNOSORBENT-ASSAY; N-ERC/MESOTHELIN; MOLECULAR-CLONING; RENAL CARCINOGENESIS; MONOCLONAL-ANTIBODY; C-ERC/MESOTHELIN; OVARIAN CANCERS; SERIAL ANALYSIS; ELISA SYSTEM; EXPRESSION;
D O I
10.1016/j.bbrc.2009.10.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:636 / 641
页数:6
相关论文
共 29 条
[1]  
Argani P, 2001, CLIN CANCER RES, V7, P3862
[2]   Transgenic rats carrying human c-Ha-ras proto-oncogenes are highly susceptible to N-methyl-N-nitrosourea mammary carcinogenesis [J].
Asamoto, M ;
Ochiya, T ;
Toriyama-Baba, H ;
Ota, T ;
Sekiya, T ;
Terada, M ;
Tsuda, H .
CARCINOGENESIS, 2000, 21 (02) :243-249
[3]   Treatment of pancreatic cancer: Challenge of the facts [J].
Beger, HG ;
Rau, B ;
Gansauge, F ;
Poch, B ;
Link, KH .
WORLD JOURNAL OF SURGERY, 2003, 27 (10) :1075-1084
[4]  
CHANG K, 1992, CANCER RES, V52, P181
[5]   ISOLATION AND CHARACTERIZATION OF A MONOCLONAL-ANTIBODY, K1, REACTIVE WITH OVARIAN CANCERS AND NORMAL MESOTHELIUM [J].
CHANG, K ;
PASTAN, I ;
WILLINGHAM, MC .
INTERNATIONAL JOURNAL OF CANCER, 1992, 50 (03) :373-381
[6]   MOLECULAR-CLONING AND EXPRESSION OF A CDNA-ENCODING A PROTEIN DETECTED BY THE K1 ANTIBODY FROM AN OVARIAN-CARCINOMA (OVCAR-3) CELL-LINE [J].
CHANG, K ;
PASTAN, I .
INTERNATIONAL JOURNAL OF CANCER, 1994, 57 (01) :90-97
[7]   Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers [J].
Chang, K ;
Pastan, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) :136-140
[8]   AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma [J].
DiMagno, EP ;
Reber, HA ;
Tempero, MA .
GASTROENTEROLOGY, 1999, 117 (06) :1464-1484
[9]   Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas [J].
Frierson, HF ;
Moskaluk, CA ;
Powell, SM ;
Zhang, H ;
Cerilli, LA ;
Stoler, MH ;
Cathro, H ;
Hampton, GM .
HUMAN PATHOLOGY, 2003, 34 (06) :605-609
[10]   Establishment of a novel specific ELISA system for rat N- and C-ERC/mesothelin. Rat ERC/mesothelin in the body fluids of mice bearing mesothelioma [J].
Hagiwara, Yoshiaki ;
Hamada, Yukiko ;
Kuwahara, Maki ;
Maeda, Masahiro ;
Segawa, Tatsuya ;
Ishikawa, Kiyoshi ;
Hino, Okio .
CANCER SCIENCE, 2008, 99 (04) :666-670