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Research ArticleExperimental Studies

Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success

SHIMPEI EGUCHI, KENJIRO KIMURA, KEN KAGEYAMA, NAOKI TANI, RYOTA TANAKA, KOHEI NISHIO, HIROJI SHINKAWA, GO OHIRA, RYOSUKE AMANO, SHOGO TANAKA, AKIRA YAMAMOTO, SHIGEKAZU TAKEMURA, MASAKAZU YASHIRO and SHOJI KUBO
Anticancer Research May 2022, 42 (5) 2395-2404; DOI: https://doi.org/10.21873/anticanres.15718
SHIMPEI EGUCHI
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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KENJIRO KIMURA
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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  • For correspondence: kenjiro@med.osaka-cu.ac.jp
KEN KAGEYAMA
2Department of Diagnostic and Interventional Radiology, Osaka City University Graduate School of Medicine, Osaka, Japan;
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NAOKI TANI
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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RYOTA TANAKA
3Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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KOHEI NISHIO
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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HIROJI SHINKAWA
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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GO OHIRA
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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RYOSUKE AMANO
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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SHOGO TANAKA
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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AKIRA YAMAMOTO
2Department of Diagnostic and Interventional Radiology, Osaka City University Graduate School of Medicine, Osaka, Japan;
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SHIGEKAZU TAKEMURA
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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MASAKAZU YASHIRO
3Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
4Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan;
5Cancer Center for Translational Research, Osaka City University Graduate School of Medicine, Osaka, Japan
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SHOJI KUBO
1Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan;
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    Figure 1.

    Macroscopic findings of each PDX model. (a) Subcutaneous engraftment, (b) pancreatic engraftment, (c) peritoneal engraftment, (d) liver engraftment.

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    Figure 2.

    Hematoxylin and eosin and immunohistochemical staining of primary (X0) and xenograft tumors (X1, X2, X3). Histological differentiation of cancer cells in X0 was maintained in X1 and X2. Furthermore, the positive staining for p53 observed in X0 was also observed in X1. αSMA staining showed no change in fiber formation in each organ. However, when X2 was passed on to X3, the amount of fiber formation was significantly decreased (p<0.01). Scale bar=200 μm.

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    Figure 3.

    Immunostaining area in PDX stroma (%). (a) CD31, (b) VEGF-A, (c) aSMA. *p<0.05.

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    Figure 4.

    Immunohistochemical staining of primary tumor and liver transplantation models. (a) X0 (hCD31; reactive human), (b) liver engraftment PDX (hCD31: reactive human), (c) liver engraftment PDX (rCD31: reactive rat), (d) liver engraftment PDX (VEGF-A).CD31, which is cross reactive in humans in which X0 stromal vessels are stained, did not stain in X1 stromal vessels (b: negative staining). In contrast, X1 stromal vessels are stained with CD31, which is cross reactive in rats (c: positive staining). (arrow: stained vascular endothelial cells). Scale bar=200 μm.

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Anticancer Research: 42 (5)
Anticancer Research
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May 2022
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Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success
SHIMPEI EGUCHI, KENJIRO KIMURA, KEN KAGEYAMA, NAOKI TANI, RYOTA TANAKA, KOHEI NISHIO, HIROJI SHINKAWA, GO OHIRA, RYOSUKE AMANO, SHOGO TANAKA, AKIRA YAMAMOTO, SHIGEKAZU TAKEMURA, MASAKAZU YASHIRO, SHOJI KUBO
Anticancer Research May 2022, 42 (5) 2395-2404; DOI: 10.21873/anticanres.15718

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Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success
SHIMPEI EGUCHI, KENJIRO KIMURA, KEN KAGEYAMA, NAOKI TANI, RYOTA TANAKA, KOHEI NISHIO, HIROJI SHINKAWA, GO OHIRA, RYOSUKE AMANO, SHOGO TANAKA, AKIRA YAMAMOTO, SHIGEKAZU TAKEMURA, MASAKAZU YASHIRO, SHOJI KUBO
Anticancer Research May 2022, 42 (5) 2395-2404; DOI: 10.21873/anticanres.15718
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Keywords

  • patient-derived xenograft
  • pancreatic ductal adenocarcinoma
  • microenvironment
  • vascular endothelial cells
  • engraftment rate
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