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Temozolomide and Pazopanib Combined with FOLFOX Regressed a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model

  1. Author:
    Zhu, Guangwei
    Zhao, Ming
    Han, Qinghong
    Tan, Yuying
    Sun, Yu
    Bouvet, Michael
    Clary, Bryan
    Singh,Shree Ram
    Ye, Jianxin
    Hoffman, Robert M

  2. Author Address

    AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350000, China., AntiCancer, Inc., San Diego, CA, USA., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA. Electronic address: singhshr@mail.nih.gov., Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350000, China. Electronic address: yejianxinfuyi@126.com., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,
    1. Year: 2020
    2. Date: Mar 03
    3. Epub Date: 2020 03 03
  2. Journal: Translational oncology
    1. 13
    2. 3
    3. Pages: 100739
  4. Type of Article: Article
  5. Article Number: 100739
  6. ISSN: 1936-5233
  1. Abstract:

    Purpose: The goal of the present study was to determine the efficacy of temozolomide (TEM) and pazopanib (PAZ) combined with FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) on a colorectal cancer patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: A colorectal cancer tumor from a patient previously established in non-transgenic nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Then labeled tumors were orthotopically implanted into the cecum of nude mice. Mice were randomized into four groups: Group 1, untreated control; group 2, TEM + PAZ; group 3, FOLFOX; group 4, TEM + PAZ plus FOLFOX. Tumor width, length, and mouse body weight were measured weekly. The Fluor Vivo imaging System was used to image the GFP-lableled tumor stromal cells in vivo. H&E staining and immunohistochemical staining were used for histological analysis. Results: All three treatments inhibited tumor growth as compared to the untreated control group. The combination of TEM+ PAZ+ FOLFOX regressed tumor growth significantly more effectively than TEM + PAZ or FOLFOX. Only the combination of TEM + PAZ + FOLFOX group caused a decrease in body weight. PAZ suppressed lymph vessels density in the colorectal cancer PDOXmousemodel suggesting inhibition of lymphangiogenesis. Conclusion: Our results suggest that the combination of TEM+ PAZ+ FOLFOX has clinical potential for colorectal cancer patient. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.tranon.2019.12.011
  3. PMID: 32143177
  4. PMCID: PMC7058405
  5. View record in Web of Science®
  6. WOS: 000535689900009
  7. PII : S1936-5233(19)30691-6

Library Notes

  1. Fiscal Year: FY2019-2020
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