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A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer.

A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Research Abstract Details 

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  • A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Abstract Text:

    james m amos-landgrafJames M Amos-Landgraf,lawrence n kwongLawrence N Kwong,christina m kendziorskiChristina M Kendziorski,mark reichelderferMark Reichelderfer,jose torrealbaJose Torrealba,jamey weichertJamey Weichert,jill d haagJill D Haag,kai-shun chenKai-Shun Chen,jordy l wallerJordy L Waller,michael n gouldMichael N Gould,william f doveWilliam F Dove,

    Progress toward the understanding and management of human colon cancer can be significantly advanced if appropriate experimental platforms become available. We have investigated whether a rat model carrying a knockout allele in the gatekeeper gene Adenomatous polyposis coli (Apc) recapitulates familial colon cancer of the human more closely than existing murine models. We have established a mutagen-induced nonsense allele of the rat Apc gene on an inbred F344/NTac (F344) genetic background. Carriers of this mutant allele develop multiple neoplasms with a distribution between the colon and small intestine that closely simulates that found in human familial adenomatous polyposis patients. To distinguish this phenotype from the predominantly small intestinal phenotype found in most Apc-mutant mouse strains, this strain has been designated the polyposis in the rat colon (Pirc) kindred. The Pirc rat kindred provides several unique and favorable features for the study of colon cancer. Tumor-bearing Pirc rats can live at least 17 months, carrying a significant colonic tumor burden. These tumors can be imaged both by micro computed tomography scanning and by classical endoscopy, enabling longitudinal studies of tumor genotype and phenotype as a function of response to chemopreventive and therapeutic regimes. The metacentric character of the rat karyotype, like that of the human and unlike the acrocentric mouse, has enabled us to demonstrate that the loss of the wild-type Apc allele in tumors does not involve chromosome loss. We believe that the Pirc rat kindred can address many of the current gaps in the modeling of human colon cancer.

    A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Publishing Authors By Initials

    jm amos-landgrafJM Amos-Landgraf,ln kwongLN Kwong,cm kendziorskiCM Kendziorski,m reichelderferM Reichelderfer,j torrealbaJ Torrealba,j weichertJ Weichert,jd haagJD Haag,ks chenKS Chen,jl wallerJL Waller,mn gouldMN Gould,wf doveWF Dove,

    For similar organic chemicals: amides: sulfonamides research abstracts see: organic chemicals: amides: sulfonamides research

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    A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 104

    Page Numbers: 4036-41

    Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

    ISSN: 0027-8424

    DAY: 27

    MONTH: 02

    YEAR: 2007

    A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7505876

    A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Keywords Mesh Terms:

    KEYWORDS: Sulfonamides

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Information

    Substance Name: celecoxib

    Registry Number: 169590-42-5

    Grant and Affiliation Information for A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer.

    AFFILIATION: Department of Biostatistics and Medical Informatics, Section of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: CA 63677

    ACRONYM: CA

    MEDLINETA: Proc Natl Acad Sci U S A

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