cholecalciferol and Multiple-Myeloma

The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed. In humans, calcium is controlled by three mechanisms: parathyroid hormone, which regulates bone resorption and renal reabsorption of calcium; calcitonin, an antagonist of parathyroid hormone; and cholecalciferol, which regulates calcium absorption from the gastrointestinal tract. Hypercalcemia of malignancy (HCM) results primarily from increased bone resorption by osteoclasts and, to a lesser extent, from increased renal tubular reabsorption. In most tumors, parathyroid hormone-related protein (PTHrP) is the primary mediator of calcium. PTHrP stimulates increased bone resorption by osteoclasts. This stimulation also activates transforming growth factor-beta (TGF-beta), which stimulates tumor cells, thus perpetuating the cycle. Hypercalcemia is usually defined as a serum calcium concentration greater than 12 mg/dL, corrected for the serum albumin concentration. In diagnosing HCM, it is important to rule out other causes of hypercalcemia, such as primary hyperparathyroidism.

Topics: Bone Resorption; Breast Neoplasms; Calcitonin; Calcium; Cholecalciferol; Female; Hematologic Neoplasms; Homeostasis; Humans; Hypercalcemia; Kidney; Lung Neoplasms; Male; Multiple Myeloma; Neoplasms; Parathyroid Hormone

Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D. Median 25(OH)D increased from 38 (IQR 32-52) nmol/L at baseline to 77 (IQR 72-87) nmol/L after 6 months (P < 0.001). Adequate 25(OH)D levels were achieved by 66% of the subjects, and 34% were within the range of 50-75 nmol/L. Furthermore, in 37% of the participants, PN severity decreased (P = 0.007).. The use of substantially higher vitamin D

Topics: Cholecalciferol; Dietary Supplements; Humans; Multiple Myeloma; Peripheral Nervous System Diseases; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins

Plasmablastic B-cell malignancies include plasmablastic lymphoma and subsets of multiple myeloma and diffuse large B-cell lymphomaDLBCL. These diseases can be difficult to diagnose and treat, and they lack well-characterized cell line models. Here, immunophenotyping and FOXP1 expression profiling identified plasmablastic characteristics in DLBCL cell lines HLY-1 and SU-DHL-9, associated with CTNNAL1, HPGD, RORA, IGF1, and/or vitamin D receptor (VDR) transcription. We demonstrated VDR protein expression in primary plasmablastic tumor cells and confirmed in cell lines expression of both VDR and the metabolic enzyme CYP27B1, which catalyzes active vitamin D3 production. Although Vdr and Cyp27b1 transcription in normal B cells were activated by interleukin 4 (IL-4) and CD40 signaling, respectively, unstimulated malignant plasmablastic cells lacking IL-4 expressed both VDR and CYP27B1. Positive autoregulation evidenced intact VDR function in all plasmablastic lines, and inhibition of growth by active vitamin D3 was both dependent on MYC protein inhibition and could be enhanced by cotreatment with a synthetic ROR ligand SR-1078. Furthermore, a VDR polymorphism, FOK1, was associated with greater vitamin D3-dependent growth inhibition. In summary, HLY-1 provides an important model of strongly plasmablastic lymphoma, and disruption of VDR pathway activity may be of therapeutic benefit in both plasmablastic lymphoma and myeloma.

Topics: Animals; Benzamides; Cell Cycle; Cell Line, Tumor; Cholecalciferol; Female; Forkhead Transcription Factors; Humans; Immunophenotyping; Mice, Inbred C57BL; Multiple Myeloma; Plasmablastic Lymphoma; Receptors, Calcitriol; Repressor Proteins

Topics: Anti-Bacterial Agents; Antineoplastic Agents; beta-Lactams; Cholecalciferol; Clinical Trials as Topic; Delivery of Health Care; Drug Industry; HSP90 Heat-Shock Proteins; Humans; Multiple Myeloma; Urologic Diseases; Vitamins

Since multiple myeloma responds poorly to conventional chemotherapy or radiotherapy, new therapeutic approaches are needed. This study investigated the effects of dexamethasone, all-trans retinoic acid (ATRA), the active metabolite of vitamin D(3) [1,25(OH)(2)D(3)] and interferon-alpha on FO mouse myeloma cells (non-immunoglobulin-secreting myeloma cell line) in single drug or drug combination groups in vitro.. Apoptosis ratio and change in cell counts in 4 single drug groups (dexamethasone, ATRA, vitamin D(3) and interferon-alpha) and 6 combination drug groups (dexamethasone + vitamin D(3,) dexamethasone + ATRA, dexamethasone + interferon-alpha, vitamin D(3) + ATRA, vitamin D(3) + interferon-alpha, interferon-alpha + ATRA) were compared with the control group.. When treatment groups were compared with the control group, there was a significant increase in apoptosis in all, but this was most prominent in the group treated with dexamethasone alone. The apoptosis ratios were 0.10 and 6.82% in the control and dexamethasone-only groups, respectively. We also found that there was a significant decrease in cell count, particularly in the dexamethasone-only, ATRA-only, and ATRA-vitamin D(3) combination groups.. ATRA, interferon-alpha, vitaminD(3) and particularly dexamethasone have significant effects on FO mouse myeloma cells resulting in a decreased cell count and an increased apoptosis ratio. This study should be repeated with human myeloma cell lines for further information.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Apoptosis; Cell Count; Cholecalciferol; Dexamethasone; Drug Interactions; Interferon-alpha; Mice; Multiple Myeloma; Tretinoin; Tumor Cells, Cultured

EB1089, a novel 1,25-dihydroxyvitamin D3 analogue, has been known to have potent antiproliferative properties in a variety of malignant cells both in vitro and in vivo. In the present study, we analysed the effect of EB1089 on NCI-H929 human myeloma cells. EB1089 inhibited cell growth of NCI-H929 and efficiently induced the G1 phase arrest of the cell cycle in a dose-dependent manner. We could also detect apoptosis in NCI-H929 cells exposed to EB1089 (1 x 10-7 M for 72 h) using the sub-G1 group of the cell cycle by FACS and annexin V binding assays. Induction of apoptosis by EB1089 was associated with down-regulation of the Bcl-2 protein without change of the Bax protein. Regarding caspase activity, which plays a crucial role in apoptosis, EB1089-treated NCI-H929 cells revealed an increased activity of caspase 3 protease accompanied by degradation of the PARP protein in a dose- and time-dependent manner. In addition, EB1089 caused the down-regulation of p44 extracellular signal-related kinase (ERK) activity and up-regulation of the p38 kinase activity during apoptosis of NCI-H929 cells. These results suggest that EB1089 inhibits growth of NCI-H929 cells via G1 cell cycle arrest as well as apoptosis by activating p38 kinase and suppressing ERK activity.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Calcitriol; Caspase 3; Caspases; Cholecalciferol; Enzyme Activation; Humans; Mitogen-Activated Protein Kinases; Multiple Myeloma; p38 Mitogen-Activated Protein Kinases; Tumor Cells, Cultured

In 70 patients with stage III multiple myeloma (MM) the authors studied spontaneous and lipopolysaccharide-induced production of interleukin-1 (IL-1) and interleukin-6 (IL-6) by blood and bone marrow mononuclear cells, concentration of parathyroid hormone and vitamin D3 in the serum. Bone marrow density was measured at photon absorption (Gambro), in patients treated with osteoprotectors bonefos and oxidevit before and after therapy (3.5-6 month course). It is shown that in MM there is a pathogenetic association between production of osteotropic IL-1, IL-6 and bone demineralization. The cases with reduced concentration of Ca and P ions in the serum (4 and 5.7% of patients, respectively) and increased PTH concentration (7%) suggest the existence of new, extratumor mechanisms of osteolysis. It is found that biphosphonates are optimal osteoprotectors. Bonefos (chlodronat, Lieras, Finland) arrests osteolysis proved by a significant increase of bone marrow density and clinical effect.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Bone Marrow; Cholecalciferol; Female; Humans; Hydroxyproline; Interleukin-1; Interleukin-6; Male; Middle Aged; Multiple Myeloma; Osteolysis; Parathyroid Hormone

The aim of the study was to evaluate the efficacy of half-year treatment of bone mineral disturbances with calcitonin in the patients with multiple myeloma. Thirty five patients (11 men and 24 women) were examined. They were treated among other with prednisone. Nineteen patients (15 patients with normal bone mineral density of lumbar spine and femoral neck and 4 with low bone mineral density who could not be treated with calcitonin) were treated only with chemotherapy. Other 16 patients with low bone mineral density have received also calcitonin (100 units subcutaneous daily) with vitamin D3 and calcium carbonate. Bone mineral density was evaluated with dual energy X-ray absorptiometry in lumbar spine and femoral neck. After treatment with calcitonin there was more pronounced influence on bone mineral density in lumbar spine and femoral neck than after treatment with chemotherapy only but the difference was not statistically significant. Because the bone mineral disturbances in the patients with multiple myeloma is the big problem there is a need for further and longer evaluation of the treatment of these disturbances.

Topics: Aged; Bone Density; Bone Diseases, Metabolic; Calcification, Physiologic; Calcitonin; Calcium Carbonate; Cholecalciferol; Female; Femur Neck; Humans; Lumbar Vertebrae; Male; Middle Aged; Multiple Myeloma; Prednisone; Radiography