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Adenovirus-based strategies enhance antitumor capability through p53-mediated downregulation of MGMT in uveal melanoma

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机构: [1]Department of Clinical Skills Center, Kunming Medical University, Kunming, Yunnan, China [2]Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
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关键词: Dacarbazine MGMT oncolytic adenovirus p53 uveal melanoma

摘要:
Uveal melanoma (UM) is an intractable disease with a low survival rates, despite adequate local treatment, as a result of its metastatic characteristics. Thus, new therapeutic strategies, including combinations of novel gene therapy and traditional chemotherapy, are under investigation to improve long-term prognosis. Dacarbazine or DTIC, an alkylating agent which results in DNA methylation, is most commonly used to treat melanoma but the response is very limited. The O6-methylguanine DNA methyl transferase (MGMT), a DNA repair protein, is involved in chemoresistance in DTIC treatment. We previously investigated a combination of oncolytic adenovirus H101 and the alkylating agent DTIC in the treatment of UM cells in vitro and observed a synergistic antitumor effect. In this study, we validated this result and report an enhanced therapeutic effect in vivo. Our findings also demonstrated that the oncolytic adenovirus H101 decreased MGMT levels via accumulation of p53 overcoming DTIC chemoresistance. Therefore, the clinical therapeutic efficacy of DTIC in the treatment of UM might be improved using this adenovirus-based combination therapy.

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出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2016]版:
Q2 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者机构: [1]Department of Clinical Skills Center, Kunming Medical University, Kunming, Yunnan, China
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通讯机构: [1]Department of Clinical Skills Center, Kunming Medical University, Kunming, Yunnan, China [*1]Department of Clinical Skills Center, Kunming Medical University, NO.1168 Chunrongxi Road, Chenggong District, Kunming, Yunnan Province 650500, P.R. China
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