Customized mitogen or antibody treatments enhance the sensitivity of lymphoid tumors to 5-fluorouracil in vitro and in vivo.
Despite impressive cure rates for certain leukemias and lymphomas, lymphoid tumors are responsible for thousands of deaths per year. Refractory disease remains difficult to control, encouraging the development of new treatment options. 5-fluorouracil (5-FU) has been successfully used to control (or cure) a variety of tumors, but has been only rarely applied to tumors of the lymphoid lineage. Here we demonstrate that the effects of 5-FU on lymphoid tumors can be enhanced by the concomitant binding of cellular membrane molecules with mitogen or antibody. When used in combination with 5-FU, mitogen treatments: (i) enhance the association of drug with cells, (ii) reduce cell proliferation in vitro and (iii) inhibit cell growth in a mouse B-cell tumor model.
D'Costa
Sybil
S
Department of Immunology, St. Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA.
Hurwitz
Julia L
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004357:Drug Synergism; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D008223:Lymphoma / Q000188:drug therapy*; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D016399:Lymphoma, T-Cell / Q000188:drug therapy; D051379:Mice; D016513:Mice, SCID; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D008934:Mitogens; D005472:Fluorouracil