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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