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Combination therapy of tumor-targeting Salmonella typhimurium A1-R and oral recombinant methioninase regresses a BRAF-V600E-negative melanoma

  1. Author:
    Kawaguchi, Kei
    Higuchi, Takashi
    Li, Shukuan
    Han, Qinghong
    Tan, Yuying
    Igarashi, Kentaro
    Zhao, Ming
    Miyake, Kentaro
    Kiyuna, Tasuku
    Miyake, Masuyo
    Ohshiro, Hiromichi
    Sugisawa, Norihiko
    Zhang, Zhiying
    Razmjooei, Sahar
    Wangsiricharoen, Sintawat
    Chmielowski, Bartosz
    Nelson, Scott D
    Russell, Tara A
    Dry, Sarah M
    Li, Yunfeng
    Eckardt, Mark A
    Singh, Arun S
    Singh, Shree Ram
    Eilber, Fritz C
    Unno, Michiaki
    Hoffman, Robert M

  2. Author Address

    AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., AntiCancer Inc, San Diego, CA, USA., Division of Hematology-Oncology, University of California, Los Angeles, CA, USA., Department of Pathology, University of California, Los Angeles, CA, USA., Division of Surgical Oncology, University of California, Los Angeles, CA, USA., Department of Surgery, Yale School of Medicine, New Haven, CT, 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., Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan. Electronic address: m_unno@surg1.med.tohoku.ac.jp., AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,
    1. Year: 2018
    2. Date: Sep 18
    3. Epub Date: 2018 08 27
  2. Journal: Biochemical and Biophysical Research Communications
    1. 503
    2. 4
    3. Pages: 3086-3092
  4. Type of Article: Article
  5. ISSN: 0006-291X
  1. Abstract:

    Melanoma is a recalcitrant cancer. To improve and individualize treatment for this disease, we previously developed a patient-derived orthotopic xenograft (PDOX) model for melanoma. We previously reported the individual efficacy of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and recombinant methioninase (rMETase) for melanoma in the PDOX models of this disease. In the present study, we evaluated the efficacy of the combination of S. typhimurium A1-R with orally-administered rMETase (o-rMETase) for BRAF-V600E-negative melanoma in a PDOX model. Three weeks after implantation, 60 PDOX mouse models were randomized into six groups of 10 mice each: untreated control, temozolomide (TEM); o-rMETase; S. typhimurium A1-R; TEM + rMETase, S. typhimurium A1-R + rMETase. All treatments inhibited tumor growth compared to untreated control (TEM: p < 0.0001, rMETase: p < 0.0001, S. typhimurium A1-R: p < 0.0001, TEM + rMETase: p < 0.0001, S. typhimurium A1-R + rMETase: p < 0.0001). The most effective was the combination of S. typhimurium A1-R + o-rMETase which regressed this melanoma PDOX, thereby indicating a new paradigm for treatment of metastatic melanoma. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.bbrc.2018.08.097
  3. PMID: 30166061
  4. View record in Web of Science®
  5. WOS: 000444791600132
  6. PII : S0006-291X(18)31781-9

Library Notes

  1. Fiscal Year: FY2017-2018
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