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Oral Recombinant Methioninase Overcomes Colorectal-cancer Liver Metastasis Resistance to the Combination of 5-Fluorouracil and Oxaliplatinum in a Patient-derived Orthotopic Xenograft Mouse Model

  1. Author:
    Oshiro, Hiromichi
    Tome, Yasunori
    Kiyuna, Tasuku
    Yoon, Sang Nam
    Lwin, Thinzar M
    Han, Qinghong
    Tan, Yuying
    Miyake, Kentaro
    Higuchi, Takashi
    Sugisawa, Norihiko
    Katsuya, Yuki
    Park, Jun Ho
    Zang, Zhiying
    Razmjooei, Sahar
    Bouvet, Michael
    Clary, Bryan
    Singh,Shree Ram
    Kanaya, Fuminori
    Nishida, Kotaro
    Hoffman, Robert M

  2. Author Address

    AntiCancer Inc., San Diego, CA, U.S.A., Department of Surgery, University of California, San Diego, CA, U.S.A., Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov., Department of Surgery, University of California, San Diego, CA, U.S.A. all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov., Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov., AntiCancer Inc., San Diego, CA, U.S.A. all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov.,
    1. Year: 2019
    2. Date: Sep
  2. Journal: Anticancer research
    1. 39
    2. 9
    3. Pages: 4667-4671
  4. Type of Article: Article
  5. ISSN: 0250-7005
  1. Abstract:

    Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p< 0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis. Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.21873/anticanres.13648
  3. PMID: 31519565
  4. View record in Web of Science®
  5. WOS: 000486457600011
  6. PII : 39/9/4667

Library Notes

  1. Fiscal Year: FY2019-2020
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