title: Rituximab-mediated sensitization of B-non-Hodgkin's lymphoma (NHL) to cytotoxicity induced by paclitaxel, gemcitabine, and vinorelbine.
abstract: Non-Hodgkin's lymphoma (NHL) responds initially to chemotherapy, however, the disease often relapses and acquires a chemoresistant phenotype. Third line treatment options such as paclitaxel, gemcitabine, and vinorelbine have been tried in patients with refractory or relapsed NHL with antilymphoma activity. Currently, rituximab (anti-CD20) has been approved for treatment of indolent NHL, with significant activity in a wide spectrum of B-cell malignancies, though a percentage of patients do not respond to rituximab treatment. Previous findings from our laboratory have demonstrated that rituximab can sensitize drug-resistant NHL B-lymphoma in vitro to some chemotherapeutic drugs. Hence, in this study, we examined the effect of combination treatment of rituximab and the drugs paclitaxel, gemcitabine, and vinorelbine on various NHL cell lines. Our findings indicate that pretreatment of NHL tumor cells with rituximab sensitizes drug-resistant NHL tumor cells to drug-mediated cytotoxicity. These findings suggest the potential clinical application of combination treatments of rituximab and paclitaxel, gemcitabine or vinorelbine in the treatment of drug/rituximab refractory non-Hodgkin's lymphoma.
authors.affiliation: Division of Oncology, Jonsson Comprehensive Cancer Center, UCLA School of Medicine, University of California, Los Angeles, CA 90095-1747, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Emmanouilides
authors.forename: Ali R
authors.initials: AR
authors.lastname: Jazirehi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonavida
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D000069283:Rituximab; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003841:Deoxycytidine; D000069283:Rituximab; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine; D000093542:Gemcitabine