Cytolytic virus activation therapy and treatment monitoring for Epstein-Barr virus associated nasopharyngeal carcinoma in a mouse tumor model

Autor: Carla F. M. Molthoff, Jos Eersels, Mariska Verlaan, Astrid E. Greijer, Jaap M. Middeldorp, Inge de Greeuw, Sandra A. W. M. Verkuijlen, Zlata Novalić
Přispěvatelé: CCA - Cancer biology and immunology, AII - Infectious diseases, Pathology, Supporting clinical sciences
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Epstein-Barr Virus Infections
Herpesvirus 4
Human
cytolytic virus activation therapy
Epstein‐Barr virus
medicine.disease_cause
infectious diseases
Deoxycytidine
Mice
0302 clinical medicine
Tumor Cells
Cultured
Targeted Cancer Therapy
Research Articles
Viral Load
PET-scan
treatment monitoring
Treatment Outcome
Lytic cycle
030220 oncology & carcinogenesis
Viral load
Research Article
medicine.drug
Ganciclovir
Nasopharyngeal neoplasm
Mice
Nude
Biology
PET‐scan
Antiviral Agents
Virus
03 medical and health sciences
Virology
medicine
Animals
Humans
Epstein-Barr virus
Epstein–Barr virus infection
Valproic Acid
EBV DNA load
nasopharyngeal carcinoma
Carcinoma
Nasopharyngeal Neoplasms
medicine.disease
Gemcitabine
Epstein–Barr virus
Disease Models
Animal
030104 developmental biology
Nasopharyngeal carcinoma
DNA
Viral
Virus Activation
Zdroj: Journal of Medical Virology, 89(12), 2207-2216. Wiley-Liss Inc.
Journal of Medical Virology
Novalić, Z, Verkuijlen, S A W M, Verlaan, M, Eersels, J L H, de Greeuw, I, Molthoff, C F M, Middeldorp, J M & Greijer, A E 2017, ' Cytolytic virus activation therapy and treatment monitoring for Epstein-Barr virus associated nasopharyngeal carcinoma in a mouse tumor model ', Journal of Medical Virology, vol. 89, no. 12, pp. 2207-2216 . https://doi.org/10.1002/jmv.24870
ISSN: 0146-6615
DOI: 10.1002/jmv.24870
Popis: Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV). Expression of viral proteins in the tumor cells is highly restricted. EBV reactivation by CytoLytic Virus Activation (CLVA) therapy triggers de novo expression of early viral kinases (PK and TK) and uses antiviral treatment to kill activated cells. The mechanism of tumor elimination by CLVA was analyzed in NPC mouse model using C666.1 cells. Valproic acid (VPA) was combined with gemcitabine (GCb) to stimulate EBV reactivation, followed by antiviral treatment with ganciclovir (GCV). A single cycle of CLVA treatment resulted in specific tumor cell killing as indicated by reduced tumor volume, loss of EBV-positive cells in situ, and paralleled by decreased EBV DNA levels in circulation, which was more pronounced than treatment with GCb alone. In vivo reactivation was confirmed by presence of lytic gene transcripts and proteins in tumors 6 days after GCb/VPA treatment. Virus reactivation was visualized by [124I]-FIAU accumulation in tumors using PET-scan. This studied showed that CLVA therapy is a potent EBV-specific targeting approach for killing tumor cells. The [124I]-FIAU appears valuable as PET tracer for studies on CLVA drug dosage and kinetics in vivo, and may find clinical application in treatment monitoring.
Databáze: OpenAIRE
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