title: Sensitization of AIDS related non-Hodgkin's B lymphoma cell lines to cytotoxic drugs toxins by interferon-gamma.
abstract: AIDS-related lymphomas (ARL) progressively become resistant to conventional chemotherapy. We have developed three B cell lines from tumor biopsies of AIDS patients with non-Hodgkin's lymphoma (NHL). The ARL cell lines were shown to be resistant to a panel of cytotoxic cytokines, toxins and drugs such as tumor necrosis factor, diphteria toxin, ricin, adriamycin, cis-platinum and anti-Fas antibody. However, when these cell lines were pretreated with low concentrations of interferon-gamma (IFN-gamma), (50 U/ml or 150 U/ml) for 24 to 48 h, the tumor cells became sensitive to these cytotoxic agents. Pretreatment of ARL with IFN-gamma stimulated proliferation while IFN-gamma inhibited the growth of ovarian tumor cell lines. Further, following treatment with IFN-gamma, the secretion of TNF-alpha by ARL lines was significantly decreased and TNF-alpha surface receptor expression was downregulated. The expression of several surface antigens on ARL was upregulated by IFN-gamma. These findings demonstrate that treatment of ARL with IFN-gamma stimulated cell proliferation, modulated several surface antigens, inhibited TNF-alpha secretion and sensitized the tumor cells to cytotoxicity by various drugs/toxins. These findings may be clinically relevant in the treatment of drug-refractory ARL.
authors.affiliation: UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. HUNTINGTON MEM HOSP,INST MOLEC MED & TECHNOL,PASADENA,CA 91105. SERV BACTERIOL VIROL B,F-59037 LILLE,FRANCE. UNIV SO CALIF,NORRIS CANC REGISTRY,SCH MED,LOS ANGELES,CA 90089.
authors.forename: A
authors.initials: A
authors.lastname: Demidem
authors.forename: Z
authors.initials: Z
authors.lastname: Salahuddin
authors.forename: T
authors.initials: T
authors.lastname: Lam
authors.forename: A
authors.initials: A
authors.lastname: Levine
authors.forename: R
authors.initials: R
authors.lastname: Khan
authors.forename: D
authors.initials: D
authors.lastname: Hober
authors.forename: B
authors.initials: B
authors.lastname: Bonavida