• Establishment of a pancreatic cancer ani

    From ScienceDaily@1:317/3 to All on Friday, April 22, 2022 22:30:48
    Establishment of a pancreatic cancer animal model using the pancreas-
    targeted hydrodynamic gene delivery method

    Date:
    April 22, 2022
    Source:
    Niigata University
    Summary:
    Pancreatic cancer has a significantly poor prognosis; therefore,
    the development of effective treatments is an unmet clinical
    need. The major drawback in this field was the lack of useful
    model animals, which delayed the establishment of markers for
    early diagnosis and therapeutic options. The research group
    established an effective carcinogenesis method with wild-type rats
    by selectively introducing oncogenes into the pancreas, using the
    pancreas-targeted hydrodynamic gene delivery method that has been
    developed by the group.



    FULL STORY ========================================================================== Pancreatic cancer has a significantly poor prognosis; therefore,
    the development of effective treatments is an unmet clinical need. The
    major drawback in this field was the lack of useful model animals, which delayed the establishment of markers for early diagnosis and therapeutic options. The research group established an effective carcinogenesis
    method with wild-type rats by selectively introducing oncogenes into the pancreas, using the pancreas-targeted hydrodynamic gene delivery method
    that has been developed by the group.


    ==========================================================================
    The research group of Professor Kamimura in Niigata University have
    established a novel pancreatic carcinogenesis model in wild-type rats
    utilizing the pancreas-targeted selective hydrodynamic gene delivery
    method developed by their research group.

    "The gene human pancreatic cancer-related gene transfer of the KRASG12Defficiently developed the pancreatic cancer," says Prof. Kamimura.

    KRASG12D-induced pancreatic intraepithelial neoplasia lesions showed
    malignant transformation in the main pancreatic duct at four weeks and developed acinar- to-ductal metaplasia, which led to pancreatic ductal adenocarcinoma within five weeks and the gene combination of KRASG12D
    and YAPenhanced these effects.

    In addition, the combination of oncogenes revealed the metastatic tumors
    in the liver, lymph nodes, etc., and invasive growth to the surrounding
    organ and tissues, mimicking the clinical course of human pancreatic
    cancer. The pancreas-targeted hydrodynamic gene delivery showed its
    efficacy in developing novel animal models and is promising methods for
    the organ specific gene therapy. Prof. Kamimura concluded that this
    pancreatic cancer model will speed up pancreatic cancer research for
    novel treatments and biomarkers for early diagnosis.

    Glossary 1. Hydrodynamic gene delivery method This method introduces a
    gene from a blood vessel of a target organ using physical force (water pressure) to express the target protein in the organ cells. Authors have reported the usefulness of this method for gene therapy for the liver
    cirrhosis etc., and developed organ-selective gene transfer methods
    such as for the liver and pancreas. and verified the procedure in large
    animals for clinical application (Kamimura K, et al. Mol Ther, 2009;
    Kamimura K, et al.

    Mol Ther, 2010; Yokoo T & Kamimura K, et al. Gene Ther, 2013; Kamimura
    K, et al. Mol Ther Nucleic Acids, 2013; Abe H & Kamimura K, et al. Mol
    Ther Nucleic Acids, 2016; Kobayashi Y & Kamimura K, et al. Mol Ther
    Nucleic Acids, 2016; Ogawa K & Kamimura K, et al. Mol Ther Nucleic
    Acids, 2017) 2. KRAS gene A member of the ras family of oncogenes,
    which transmits cell proliferation signals to the cell nucleus and
    promotes cell proliferation. Mutations in this gene (e.g. KRASG12D)
    play an important role in promoting carcinogenesis.

    3. YAP gene The YAP (yes-associated protein) gene is one oncogene that functions in various human cancers. Involved in cell proliferation as
    a transcription factor, the YAP is also reported to be inhibited by
    the Hippo signaling pathway, which enables controlling organ size and suppressing tumors.


    ========================================================================== Story Source: Materials provided by Niigata_University. Note: Content
    may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Osamu Shibata, Kenya Kamimura, Yuto Tanaka, Kohei Ogawa, Takashi
    Owaki,
    Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Hiroyuki Abe, Satoshi
    Ikarashi, Kazunao Hayashi, Takeshi Yokoo, Shuji Terai. Establishment
    of a pancreatic cancer animal model using the pancreas-targeted
    hydrodynamic gene delivery method. Molecular Therapy - Nucleic
    Acids, 2022; 28: 342 DOI: 10.1016/j.omtn.2022.03.019 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220422094328.htm

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