cholecalciferol and Lymphoma--Large-B-Cell--Diffuse

Topics: Animals; Cell Differentiation; Cholecalciferol; Cytokines; Humans; Lymphoma, Large B-Cell, Diffuse; Macrophages; Models, Biological; Monocytes; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Cells, Cultured

Vitamin D deficiency has been reported to be a negative prognostic factor in elderly patients with aggressive B-cell lymphomas. In vitro data suggest that vitamin D supplementation may enhance rituximab-mediated cytotoxicity. We prospectively assessed 25-hydroxyvitamin D [25(OH)D] levels at diagnosis in a cohort of 155 patients with aggressive B-cell lymphomas of whom 128 had diffuse large B-cell lymphoma (DLBCL) not otherwise specified. 25(OH)D levels were deficient (<20 ng/mL) in 105 (67%), insufficient (20-29 ng/mL) in 32 (21%), and normal (≥30 ng/mL) in 18 (12%) patients with a seasonal variation. Patient characteristics associated with lower 25(OH)D levels were poor performance status, overweight, B-symptoms, elevated LDH, lower albumin and hemoglobin levels. As a result of a change in practice pattern, 116 patients received vitamin D3 (cholecalciferol) supplementation that included a loading phase with daily replacement and subsequent maintenance phase with a weekly dose of 25,000 IU until end of treatment. This resulted in a significant increase in 25(OH)D levels, with normalization in 56% of patients. We analyzed the impact of 25(OH)D levels on event-free survival in patients treated with Rituximab-CHOP. 25(OH)D levels below 20 ng/mL at diagnosis and IPI were independently associated with inferior EFS. Moreover, patients with normalized 25(OH)D levels following supplementation showed better EFS than patients with persistently deficient/insufficient 25(OH)D levels. Our study provides the first evidence that achievement of normal 25(OH)D levels after vitamin D3 supplementation is associated with improved outcome in patients with DLBCL and deficient/insufficient 25(OH)D levels when receiving rituximab-based treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cholecalciferol; Cyclophosphamide; Dietary Supplements; Disease-Free Survival; Doxorubicin; Female; Humans; Immunotherapy; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Rituximab; Treatment Outcome; Vincristine; Vitamin D; Vitamin D Deficiency

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antibody-Dependent Cell Cytotoxicity; Antineoplastic Agents, Immunological; Case-Control Studies; Cholecalciferol; Cytotoxicity, Immunologic; Female; Healthy Volunteers; Humans; Killer Cells, Natural; Lymphocyte Activation; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Rituximab

The human histiocytic lymphoma cell line U937 can be induced to differentiate along the monocyte/macrophage pathway by either phorbol myristate acetate (PMA) or by the combination of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (VD). U937 cells treated with either PMA or RA/VD were able to phagocytose Salmonella typhimurium in the presence of non-immune human serum. However, only cells differentiated by RA/VD were capable of developing an oxidative metabolic burst in response to infection. Since the oxidative burst is considered to be a potent antimicrobial mechanism, we investigated its effect on S. typhimurium. The oxidative burst failed to affect either the viability or the multiplication of S. typhimurium suggesting that it plays only a minor role in the host defence against S. typhimurium.

Topics: Cell Differentiation; Cholecalciferol; Humans; Lymphoma, Large B-Cell, Diffuse; Phagocytosis; Respiratory Burst; Salmonella typhimurium; Tretinoin; Tumor Cells, Cultured

A monoblastic cell line U-937 (clone 4), was induced to differentiate along the monocytoid lineage by 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid (RA), and vitamin D3 (VD3). By immunochemical and morphological criteria the cells were found to differentiate into macrophage-like cells in the presence of all three inducers. The expression of proteoglycans was investigated in control cultures and in cells differentiated in the presence of both TPA, RA, and VD3. The cells were labeled with [35S]sulfate and cell and medium-associated 35S-macromolecules were either solubilized in sodium dodecyl sulfate or subjected to proteolytic digestion. By use of chondroitinase ABC digestions and deaminative cleavage at pH 1.5 it was demonstrated that all cell cultures incorporated [35S]sulfate exclusively into chondroitin sulfate proteoglycan (CSPG). The expression of CSPG was found to decrease with differentiation to 60% in the presence of TPA, 67% in RA, and 40% in VD3 of control cultures on a cellular basis. The CSPG synthesized was consistently recovered from the medium fractions, whereas free glycosaminoglycan (GAG) chains were found in the cell fraction in all the cell cultures. GAG chains from both control and TPA-, RA-, and VD3-induced cultures were found to be exclusively of the chondroitin 4-sulfate type. However, the CSPGs from RA- and VD3-treated cells were found to differ in molecular size from those of control and TPA-induced cultures, as judged by Sepharose CL-6B gel chromatography. This difference in macromolecular properties following the induced differentiation of the monoblastic cells into macrophage-like cells was found to reside in expression of CSPGs (in the presence of RA and VD3) with smaller GAG chains. Control cells and TPA-induced cells synthesized CSPGs with GAG chains of approximate Mr of 30,000, contrasted by approximate Mr of 17,000 and 16,000 in RA- and VD3-induced cells, respectively. Accordingly, all three agents used in this study were found to induce differentiation of the U-937-4 cells and a decrease in the expression of CSPG, but only RA and VD3 were found to influence the structure of the proteoglycans synthesized.

Topics: Cell Differentiation; Cholecalciferol; Chondroitin; Chondroitin Sulfates; Glycosaminoglycans; Humans; Lymphoma, Large B-Cell, Diffuse; Monocytes; Proteoglycans; Tetradecanoylphorbol Acetate; Tretinoin

Topics: Animals; Cholecalciferol; Drug Therapy; Humans; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms; Sarcoma