1. Development of a novel inducer for EBV lytic therapy
- Author
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James C. Romero-Masters, Shannon C. Kenney, Poli Adi Narayana Reddy, Nicholas Paparoidamis, Paul M. Lieberman, Farheen Sultana Mohammed, Xin Feng, Joseph M. Salvino, and Nadezhda Tikhmyanova
- Subjects
Herpesvirus 4, Human ,Clinical Biochemistry ,Population ,Pharmaceutical Science ,Antineoplastic Agents ,medicine.disease_cause ,Antiviral Agents ,Biochemistry ,Article ,Virus ,Small Molecule Libraries ,Mice ,Structure-Activity Relationship ,Drug Development ,Stomach Neoplasms ,Antiretroviral Therapy, Highly Active ,hemic and lymphatic diseases ,Drug Discovery ,medicine ,Animals ,Cytotoxic T cell ,education ,Molecular Biology ,education.field_of_study ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Lymphoblast ,digestive, oral, and skin physiology ,Organic Chemistry ,medicine.disease ,Epstein–Barr virus ,digestive system diseases ,Virus Latency ,Disease Models, Animal ,Nasopharyngeal carcinoma ,Lytic cycle ,Cell culture ,Cancer research ,Molecular Medicine - Abstract
Epstein-Barr virus (EBV) is a human herpesvirus that infects over 90% of the world's population that persists as a latent infection in various lymphoid and epithelial malignancies. The total number of EBV associated malignancies is estimated to exceed 200,000 new cancers per year. Current chemotherapeutic treatments of EBV-positive cancers include broad-spectrum cytotoxic drugs that ignore the EBV positive status of tumors and have limited safety and selectivity. In an effort to develop new and more efficacious molecules for inducing EBV reactivation, we have developed high-throughput screening assays to identify a class of small molecules (referred to as the C60 series) that efficiently activate the EBV lytic cycle in multiple latency types, including lymphoblastoid and nasopharyngeal carcinoma cell lines. In this paper we report our preliminary structure activity relationship studies and demonstrate reactivation of EBV in the SNU719 gastric carcinoma mouse model and the AGS-Akata gastric carcinoma mouse model.
- Published
- 2019
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