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Recombinant methioninase in combination with DOX overcomes first-line DOX resistance in a patient-derived orthotopic xenograft nude-mouse model of undifferentiated spindle-cell sarcoma

  1. Author:
    Igarashi, Kentaro
    Kawaguchi, Kei
    Li, Shukuan
    Han, Qinghong
    Tan, Yuying
    Murakami, Takashi
    Kiyuna, Tasuku
    Miyake, Kentaro
    Miyake, Masuyo
    Singh, Arun S
    Eckhardt, Mark A
    Nelson, Scott D
    Russell, Tara A
    Dry, Sarah M
    Li, Yunfeng
    Yamamoto, Norio
    Hayashi, Katsuhiro
    Kimura, Hiroaki
    Miwa, Shinji
    Tsuchiya, Hiroyuki
    Singh, Shree Ram
    Eilber, Fritz C
    Hoffman, Robert M

  2. Author Address

    AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan., AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, USA., Division of Hematology-Oncology, University of California, Los Angeles, CA, USA., Department of Surgery, Yale School of Medicine, New Haven, CT, USA., Department of Pathology, University of California, Los Angeles, CA, USA., Division of Surgical Oncology, University of California, Los Angeles, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Division of Surgical Oncology, University of California, Los Angeles, CA, USA. Electronic address: fceilber@mednet.ucla.edu., AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,
    1. Year: 2018
    2. Date: MAR 28
    3. Epub Date: 2018 01 03
  2. Journal: Cancer Letters
    1. 417
    2. Pages: 168-173
  4. Type of Article: Article
  5. ISSN: 0304-3835
  1. Abstract:

    We have previously established a patient-derived orthotopic xenograft (PDOX) model of undifferentiated spindle cell sarcoma (USCS). Recombinant methioninase (rMETase) has previously demonstrated efficacy in PDOX mouse models of human cancers. In the present study, we determined if rMETase in combination with doxorubicin (DOX) can overcome first-line DOX resistance in a PDOX models of USCS. The USCS PDOX mouse models were randomized into the following groups when tumor volume reached 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks); G3, rMETase (100 units/mouse, i.p., daily, for 2 weeks); G4, DOX (3 mg/kg, i.p., weekly, for 2 weeks) combined with rMETase (100 units/mouse, i.p., daily, for 2 weeks). Tumor size and body weight were measured twice a week. On day 14 after initiation, the USCS PDOX tumor sizes were (G1): 360 ± 85 mm3; DOX (G2): 355 ± 111 mm3, p = .927; rMETase (G3): 182 ± 57 mm3, p = .0003; DOX + rMETase (G4): 134 ± 29 mm3, p = .00001. These results indicate that rMETase can overcome USCS resistance to DOX, which is first line therapy for this disease. The body weight of treated mice was not significantly different in each group. The present results demonstrate the power of the PDOX model to identify effective therapy for recalcitrant cancer and the potential of rMETase to overcome DOX resistance. Copyright © 2018. Published by Elsevier B.V.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.canlet.2017.12.028
  3. PMID: 29306021
  4. View record in Web of Science®
  5. WOS: 000425071000017
  6. PII : S0304-3835(18)30001-6

Library Notes

  1. Fiscal Year: FY2017-2018
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