Overcoming drug/cytokine resistance of AIDS-associated NHL cells following treatment with IFN-gamma in vitro (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Overcoming drug/cytokine resistance of AIDS-associated NHL cells following treatment with IFN-gamma in vitro (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A2001 1994. Unique Identifier : AIDSLINE ICDB/95603687
Demidem A; Salahuddin Z; Lam T; Nakamura S; Levine A; Khan RS; Jewett A; Bonavida B; University of California, Los Angeles, CA 90024

Abstract: Non-Hodgkin's B Lymphomas (NHL) progressively become resistant to conventional chemotherapy. Several new approaches were undertaken to test reversal of resistance of NHL. We have developed B cell lines from the tumor biopsies of AIDS patients with NHL. The NHL cell lines were shown to be resistant to a panel of cytokines and/or drugs such as TNF-alpha, diphtheria toxin (DTX), ricin, Adriamycin, CDDP, and anti-Fas antibody. However, when these cell lines were pretreated with low concentrations of IFN-gamma (50 U/ml or 150 U/ml) for 24 to 48 hr they became sensitive to treatment with these cytotoxic agents. In addition, under these conditions, cell-mediated apoptosis was observed. Pretreatment with IFN-gamma resulted in further growth enhancement of these B cells while acting as an anti-proliferative agent on the ovarian tumor cell lines. Pentoxifylline (PTX) treatment of NHL cells decreased TNF-alpha secretion and resulted in overcoming the resistance to CDDP. Further, following treatment with IFN-gamma, the secretion of TNF-alpha by NHL lines was significantly decreased as well as TNF-alpha receptor expression was downregulated. These findings demonstrate that NHL cell lines pretreated with IFN-gamma or PTX resulted in enhanced proliferative response with concurrent decrease of TNF-alpha secretion and resulted in sensitization of the cells to drugs/toxins. These studies also suggest that TNF-alpha could be one of the cytokines regulating drug resistance.

Keywords: Antineoplastic Agents/*TOXICITY Biopsy Cell Division/DRUG EFFECTS Cell Line Cisplatin/TOXICITY Comparative Study Cytokines/*TOXICITY Diphtheria Toxin/TOXICITY Doxorubicin/TOXICITY Drug Resistance Female Human Interferon Type II/*PHARMACOLOGY Lymphoma, AIDS-Related/*PATHOLOGY Ovarian Neoplasms Pentoxifylline/*TOXICITY Ricin/TOXICITY Tumor Cells, Cultured Tumor Necrosis Factor/BIOSYNTHESIS/TOXICITY ABSTRACT
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M9521048

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