Combination treatment with recombinant methioninase enables temozolomide to arrest a BRAF V600E melanoma in a patient-derived orthotopic xenograft (PDOX) mouse model
| العنوان: | Combination treatment with recombinant methioninase enables temozolomide to arrest a BRAF V600E melanoma in a patient-derived orthotopic xenograft (PDOX) mouse model |
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| المؤلفون: | Fritz C. Eilber, Sarah M. Dry, Qinghong Han, Takashi Murakami, Kentaro Miyake, Scott D. Nelson, Michiaki Unno, Shukuan Li, Robert M. Hoffman, Yunfeng Li, Bartosz Chmielowski, Kentaro Igarashi, Kei Kawaguchi, Tara A. Russell, Yuying Tan, Tasuku Kiyuna |
| المصدر: | Oncotarget, vol 8, iss 49 Oncotarget |
| بيانات النشر: | Impact Journals, LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, medicine.medical_specialty, Combination therapy, Oncology and Carcinogenesis, temozolomide, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nude mouse, Surgical oncology, law, Internal medicine, melanoma, medicine, metabolic targeting, methionine dependence, Temozolomide, Methionine, biology, business.industry, Melanoma, Cancer, recombinant methioninase, biology.organism_classification, medicine.disease, 3. Good health, Surgery, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Recombinant DNA, business, Research Paper, medicine.drug |
| الوصف: | // Kei Kawaguchi 1, 2, 3 , Kentaro Igarashi 1, 2 , Shukuan Li 1 , Qinghong Han 1 , Yuying Tan 1 , Tasuku Kiyuna 1, 2 , Kentaro Miyake 1 , 2 , Takashi Murakami 1, 2 , Bartosz Chmielowski 4 , Scott D. Nelson 5 , Tara A. Russell 6 , Sarah M. Dry 5 , Yunfeng Li 5 , Michiaki Unno 3 , Fritz C. Eilber 6 and Robert M. Hoffman 1, 2 1 AntiCancer, Inc., San Diego, CA, USA 2 Department of Surgery, University of California, San Diego, CA, USA 3 Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan 4 Division of Hematology-Oncology, University of California, Los Angeles, CA, USA 5 Department of Pathology, University of California, Los Angeles, CA, USA 6 Division of Surgical Oncology, University of California, Los Angeles, CA, USA Correspondence to: Robert M. Hoffman, email: all@anticancer.com Fritz C. Eilber, email: fceilber@mednet.ucla.edu Keywords: recombinant methioninase, methionine dependence, metabolic targeting, temozolomide, melanoma Received: June 06, 2017 Accepted: July 06, 2017 Published: August 12, 2017 ABSTRACT An excessive requirement for methionine termed methionine dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by methionine deprivation such as with recombinant methioninase (rMETase). The present study used a previously-established patient-derived orthotopic xenograft (PDOX) nude mouse model of BRAF V600E-mutant melanoma to determine the efficacy of rMETase in combination with a first-line melanoma drug, temozolomide (TEM). In the present study 40 melanoma PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n=10); TEM (25 mg/kg, oral 14 consecutive days, n=10); rMETase (100 units, intraperitoneal 14 consecutive days, n=10); combination TEM + rMETase (TEM: 25 mg/kg, oral rMETase: 100 units, intraperitoneal 14 consecutive days, n=10). All treatments inhibited tumor growth compared to untreated control (TEM: p =0.0081, rMETase: p =0.0037, TEM-rMETase: p =0.0024) on day 14 after initiation. However, the combination therapy of TEM and rMETase was significantly more efficacious than either mono-therapy (TEM: p =0.0051, rMETase: p =0.0051). The present study is the first demonstrating the efficacy of rMETase combination therapy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as melanoma, where rMETase may enhance first-line therapy. |
| وصف الملف: | application/pdf |
| تدمد: | 1949-2553 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5657a1113de9ec7018a5035eba1757bTest https://doi.org/10.18632/oncotarget.20231Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a5657a1113de9ec7018a5035eba1757b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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