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Peritoneal Metastases in a Patient-derived Orthotopic Xenograft (PDOX) Model of Colon Cancer Imaged Non-invasively via Red Fluorescent Protein Labeled Stromal Cells.

Authors
  • Park, Jun Ho1, 2, 3
  • Zhao, Ming1
  • Oshiro, Hiromichi1, 2
  • Miyake, Kentaro1, 2
  • Higuchi, Takashi1, 2
  • Reynoso, Jose1
  • Razmjooei, Sahar1
  • Bouvet, Michael2
  • Clary, Bryan2
  • Zhang, Zhiying1, 2
  • Sugisawa, Norihiko1, 2
  • Yamamoto, Jun1, 2
  • Singh, Shree Ram4
  • Hoffman, Robert M5, 2
  • 1 AntiCancer Inc., San Diego, CA, U.S.A.
  • 2 Department of Surgery, University of California, San Diego, CA, U.S.A.
  • 3 Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea. , (North Korea)
  • 4 Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. [email protected] [email protected]
  • 5 AntiCancer Inc., San Diego, CA, U.S.A. [email protected] [email protected]
Type
Published Article
Journal
Anticancer Research
Publisher
International Institute of Anticancer Research
Publication Date
Jul 01, 2019
Volume
39
Issue
7
Pages
3463–3467
Identifiers
DOI: 10.21873/anticanres.13492
PMID: 31262870
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Patient-derived orthotopic xenograft (PDOX) models have patient-like clinical features and may be imaged, in case of some cancers, by passaging of the tumors through transgenic nude mice expressing red-fluorescent protein (RFP) where they stably acquire RFP expressing stroma. The aim of the present study was to quantify red fluorescent area and intensity in colon-cancer peritoneal metastases in PDOX models in non-transgenic nude mice after passage in RFP transgenic nude mice by non-invasive external fluorescence imaging. Tumor fragments originating from a colon cancer patient with peritoneal metastases were implanted in transgenic RFP nude mice. Resultant tumors were harvested, and fragments were implanted in the same strain a second time. Passaged tumors stably acquired RFP-expressing stroma from their transgenic hosts. The tumor with RFP-expressing stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. At eight weeks post-implantation, non-invasive external RFP images were obtained. RFP area and intensity were measured and correlated with tumor weight and volume. Metastatic patient colon cancer can be stably and brightly labeled by passage in transgenic RFP-expressing nude mice such that tumor growth could be non-invasively imaged. Tumor growing could be non-invasively imaged when passaged to non-transgenic nude mice. A strong correlation between fluorescence intensity and area values with tumor weight and volume were established by external fluorescence imaging. This new tumor model of metastatic colon cancer can be used to evaluate novel therapeutics in real time for this recalcitrant disease. Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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