دورية أكاديمية
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: | Kawaguchi, Kei, Igarashi, Kentaro, Li, Shukuan, Han, Qinghong, Tan, Yuying, Kiyuna, Tasuku, Miyake, Kentaro, Murakami, Takashi, Chmielowski, Bartosz, Nelson, Scott D, Russell, Tara A, Dry, Sarah M, Li, Yunfeng, Unno, Michiaki, Eilber, Fritz C, Hoffman, Robert M |
| المصدر: | Oncotarget, vol 8, iss 49 |
| بيانات النشر: | eScholarship, University of California |
| سنة النشر: | 2017 |
| المجموعة: | University of California: eScholarship |
| مصطلحات موضوعية: | melanoma, metabolic targeting, methionine dependence, recombinant methioninase, temozolomide, Cancer, Brain Disorders, Biotechnology, Oncology and Carcinogenesis |
| جغرافية الموضوع: | 85516 - 85525 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | qt30g181d3; https://escholarship.org/uc/item/30g181d3Test; https://escholarship.org/content/qt30g181d3/qt30g181d3.pdfTest |
| DOI: | 10.18632/oncotarget.20231 |
| الإتاحة: | https://doi.org/10.18632/oncotarget.20231Test https://escholarship.org/uc/item/30g181d3Test https://escholarship.org/content/qt30g181d3/qt30g181d3.pdfTest |
| حقوق: | public |
| رقم الانضمام: | edsbas.A610A9A7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.18632/oncotarget.20231 |
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