Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
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PMID:Noncalcemic actions of vitamin D receptor ligands. 1579 98

Myelodysplastic syndrome (MDS) is often a pernicious disorder associated with pancytopenia in the elderly; therapeutic approaches need to balance their toxicities versus the symptoms of the disease. 1,25(OH)(2)-Vitamin-D(3) [1,25(OH)(2)D(3)] inhibits proliferation and induces differentiation of leukemic cells in vitro. Small clinical trials of 1,25(OH)(2)D(3) have shown modest efficacy in MDS; hypercalcemia prevented the administration of doses that have been shown to be effective in vitro. Paricalcitol [19-nor-1,25(OH)(2)D(2), Zemplar] has been approved by the FDA for treatment of secondary hyperparathyroidism. This Vitamin D analog is unique because it has little hypercalcemic potential; but in vitro, it has strong anti-leukemic activity. We conducted a clinical trial of oral paricalcitol to 12 MDS patients whose disease varied between an IPSS of low to high. Drug was well-tolerated in all patients. No responses were observed according to international working group (IWG) criteria. However, the platelet count of 1 of the 12 individuals rose from 53,500 to 120,000/microl blood over 5 weeks; but the patient succumbed to a fatal fungal infection. In summary, paricalcitol given as a single agent to MDS patients is therapeutically not very efficacious; further trials of the Vitamin D analog should be considered in combination with other approaches.
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PMID:Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome. 1616 82

Anemia is one of the most common problems in chronic kidney disease (CKD). Despite comprehensive investigations in several cases, definite causes of anemia frequently remain unknown. Our study aimed to analyze the factors that possibly affect anemia in CKD patients who were referred for hematology consultation. A total of 87 patients were retrospectively included in the cohort. Forty-four cases were excluded, including 30 cases with unavailable intact parathyroid hormone (iPTH) data, 11 cases with bone marrow diseases (8 Pure red cell aplasia, 3 Myelodysplastic syndrome) and 3 cases with thalassemia. In total, 43 patients were analyzed. Patients with high iPTH had a significantly lower Hemoglobin (Hb) level and required a higher dose of erythropoiesis stimulating agents (ESAs) compared with the normal iPTH group (Hb 8.29 vs 9.24 mg/dL, P=0.032 and ESAs dose of 16,352.94 vs. 12,444.44 U/week, P=0.024). Univariate, followed by stepwise multivariate analysis was performed and determined that serum phosphate (PO4) was significantly associated with lower Hb level (P=0.01 and P=0.013, respectively). In addition, Hb level was inversely correlated with iPTH and serum phosphate (PO4) level (r=-0.54, P<0.001 and r=-0.47, P=0.005; respectively). Mineral disequilibrium is an important factor associated with anemia in ESA hyporesponsive CKD. Also, hyperphosphatemia and secondary hyperparathyroidism are significantly correlated with low Hb. As a result, we strongly suggest correction of mineral disequilibrium factors prior to performing bone marrow study.
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PMID:Factors associated with erythropoiesis-stimulating agent hyporesponsiveness anemia in chronic kidney disease patients. 3157 7