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Targeted therapy for Epstein-Barr virus-associated gastric carcinoma using low-dose gemcitabine-induced lytic activation.
Lee, Hyun Gyu; Kim, Hyemi; Kim, Eun Jung; Park, Pil-Gu; Dong, Seung Myung; Choi, Tae Hyun; Kim, Hyunki; Chong, Curtis R; Liu, Jun O; Chen, Jianmeng; Ambinder, Richard F; Hayward, S Diane; Park, Jeon Han; Lee, Jae Myun.
Afiliación
  • Lee HG; Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim H; Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim EJ; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Park PG; Radiopharmaceutical Research Team, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
  • Dong SM; Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Choi TH; Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea.
  • Kim H; Radiopharmaceutical Research Team, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
  • Chong CR; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Liu JO; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, MA, USA.
  • Chen J; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, MA, USA.
  • Ambinder RF; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hayward SD; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Park JH; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lee JM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Oncotarget ; 6(31): 31018-29, 2015 Oct 13.
Article en En | MEDLINE | ID: mdl-26427042
The constant presence of the viral genome in Epstein-Barr virus (EBV)-associated gastric cancers (EBVaGCs) suggests the applicability of novel EBV-targeted therapies. The antiviral nucleoside drug, ganciclovir (GCV), is effective only in the context of the viral lytic cycle in the presence of EBV-encoded thymidine kinase (TK)/protein kinase (PK) expression. In this study, screening of the Johns Hopkins Drug Library identified gemcitabine as a candidate for combination treatment with GCV. Pharmacological induction of EBV-TK or PK in EBVaGC-originated tumor cells were used to study combination treatment with GCV in vitro and in vivo. Gemcitabine was found to be a lytic inducer via activation of the ataxia telangiectasia-mutated (ATM)/p53 genotoxic stress pathway in EBVaGC. Using an EBVaGC mouse model and a [125I] fialuridine (FIAU)-based lytic activation imaging system, we evaluated gemcitabine-induced lytic activation in an in vivo system and confirmed the efficacy of gemcitabine-GCV combination treatment. This viral enzyme-targeted anti-tumor strategy may provide a new therapeutic approach for EBVaGCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Neoplasias Gástricas / Carcinoma / Protocolos de Quimioterapia Combinada Antineoplásica / Ganciclovir / Herpesvirus Humano 4 / Infecciones por Virus de Epstein-Barr / Desoxicitidina / Terapia Molecular Dirigida / Antimetabolitos Antineoplásicos Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Oncotarget Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Neoplasias Gástricas / Carcinoma / Protocolos de Quimioterapia Combinada Antineoplásica / Ganciclovir / Herpesvirus Humano 4 / Infecciones por Virus de Epstein-Barr / Desoxicitidina / Terapia Molecular Dirigida / Antimetabolitos Antineoplásicos Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Oncotarget Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos