methylcellulose and Multiple-Myeloma

Topics: Acute Disease; Agar; Animals; B-Lymphocytes; Cells, Cultured; Chronic Disease; Colony-Forming Units Assay; Humans; Leukemia, Lymphoid; Methylcellulose; Multiple Myeloma

TRAIL, the ligand for the newly discovered DR-4 and DR-5 receptor, is a member of the TNF family of death signal transduction proteins with a mechanism of cell death similar to that of Fas and Fas ligand (Fas-L) system. We provide first time evidence that TRAIL is a potent inducer of apoptosis in multiple myeloma (MM) cell lines. TRAIL effectively induced extensive apoptosis in 8226 and ARP-1 MM cells in a time- and dose-dependent manner. Apoptosis with TRAIL reached about 80% within 48 h of treatment with a dose of 160 ng/ml. Furthermore, we provide first time evidence that similar to Fas, TRAIL-induced apoptosis is not blocked by bcl-2 in MM cell lines. Most importantly, TRAIL induced substantial apoptosis in freshly isolated, flow-sorted myeloma cells obtained from different MM patients expressing variable levels of bcl-2. Finally, we demonstrate for the first time that TRAIL is not cytotoxic to purified CD34+/CD45dim hematopoietic stem cells and does not inhibit CFU-GM or BFU-E colony formation in methylcellulose.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Antigens, CD; Antigens, CD34; Antigens, Differentiation; Apoptosis; Apoptosis Regulatory Proteins; Cell Division; Cells, Cultured; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Flow Cytometry; Genes, bcl-2; Hematopoietic Stem Cells; Humans; Leukocyte Common Antigens; Membrane Glycoproteins; Methylcellulose; Multiple Myeloma; NAD+ Nucleosidase; Paclitaxel; Proto-Oncogene Proteins c-bcl-2; Time Factors; TNF-Related Apoptosis-Inducing Ligand; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Seven patients with refractory multiple myeloma (readily evaluable for response) were treated in a Phase II trial with poly(I,C)-LC using a 3 times per week intravenous schedule. Serial immunologic testing included assessment of natural killer (NK) cell activity, antibody-dependent cytotoxicity, delayed hypersensitivity, and in vitro mitogen responses. One patient had a partial response (PR) of 6-month duration, and 3 other patients had objective responses (less than PR). Significant interferon induction occurred, but levels dropped substantially with serial dosing. Major toxicity included hypertension, hypotension, fever, and myelosuppression. The demonstration of modulation of myeloma progression in this refractory population was encouraging.

Topics: Adult; Aged; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Humans; Interferon Inducers; Male; Methylcellulose; Middle Aged; Multiple Myeloma; Poly I-C; Polylysine; Waldenstrom Macroglobulinemia

Topics: Absorption; Animals; Antibodies, Anti-Idiotypic; Antibody-Producing Cells; Antigens; Erythrocytes; Hemolytic Plaque Technique; Immunization, Secondary; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Methylcellulose; Mice; Micromanipulation; Multiple Myeloma; Neoplasm Proteins; Rabbits; Sheep

Topics: Aged; Animals; Antibodies, Anti-Idiotypic; Arthritis, Rheumatoid; Bence Jones Protein; Cell Division; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Horses; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Male; Melphalan; Methylcellulose; Multiple Myeloma; Plasma Cells; Rheumatoid Factor