| Literature DB >> 30166061 |
Kei Kawaguchi1, Takashi Higuchi2, Shukuan Li3, Qinghong Han3, Yuying Tan3, Kentaro Igarashi2, Ming Zhao3, Kentaro Miyake2, Tasuku Kiyuna2, Masuyo Miyake2, Hiromichi Ohshiro2, Norihiko Sugisawa1, Zhiying Zhang2, Sahar Razmjooei3, Sintawat Wangsiricharoen3, Bartosz Chmielowski4, Scott D Nelson5, Tara A Russell6, Sarah M Dry5, Yunfeng Li5, Mark A Eckardt7, Arun S Singh4, Shree Ram Singh8, Fritz C Eilber9, Michiaki Unno10, Robert M Hoffman11.
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.Entities:
Keywords: BRAF-V600E-negative melanoma; Methionine dependence; Nude mice; PDOX; Precision therapy; Recombinant methioninase; Salmonella typhimurium A1-R
Mesh:
Substances:
Year: 2018 PMID: 30166061 DOI: 10.1016/j.bbrc.2018.08.097
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN: 0006-291X Impact factor: 3.575