title: Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.
abstract: BACKGROUND
  Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans.
  
  
  RESULTS
  Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice.
  
  
  CONCLUSIONS
  These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hiba
authors.initials: H
authors.lastname: El Hajj
authors.forename: Jihane
authors.initials: J
authors.lastname: Ali
authors.forename: Akram
authors.initials: A
authors.lastname: Ghantous
authors.forename: Dana
authors.initials: D
authors.lastname: Hodroj
authors.forename: Ahmad
authors.initials: A
authors.lastname: Daher
authors.forename: Kazem
authors.initials: K
authors.lastname: Zibara
authors.forename: Chloé
authors.initials: C
authors.lastname: Journo
authors.forename: Zaher
authors.initials: Z
authors.lastname: Otrock
authors.forename: Ghazi
authors.initials: G
authors.lastname: Zaatari
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
authors.forename: Marwan
authors.initials: M
authors.lastname: El Sabban
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
authors.forename: Raghida
authors.initials: R
authors.lastname: Abou Merhi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D054685:Lymphoma, Primary Effusion / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D051379:Mice; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D016898:Interferon-alpha; D001151:Arsenic