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

Intensity and specificity of leukocyte endothelial interaction may differ in various subtypes of myelodysplastic syndromes. To assess endothelial activation, plasma levels of endothelial adhesion molecules (E-selectin, VCAM-1 and ICAM-1) were analyzed in 65 patients with MDS using commercially available immunoassays. In MDS patients, high levels of sVCAM-1 were closely related to circulation of monocytic cells in the peripheral blood and splenic enlargement. Patients with CMML showed the highest sE-selectin, sICAM-1 and sVCAM-1 levels, whereas receptor levels in low-risk MDS (RA, RARS) were not significantly different from those in high-risk MDS (RAEB, RAEB-t). Similar receptor concentrations were measured in bone marrow aspirations and samples from peripheral blood. Based on levels of circulating endothelial adhesion molecules there is no clear-cut evidence for a general endothelial cell activation in MDS. Furthermore, levels of circulating endothelial adhesion molecules had no prognostic significance in MDS. Concerning MDS subtypes, patients with CMML demonstrate the highest endothelial activation based on cCAM levels obtained. Thus, increased leukocyte endothelial interaction may account for the higher incidence of extramedullary infiltrations in this MDS subtype.
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PMID:Levels of circulating endothelial adhesion molecules in patients with myelodysplastic syndromes. 1174 59

The aim of this study was to assess circulating soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and interleukin-1beta (IL-1beta) in myelodysplastic syndromes (MDS) in order to evaluate their clinical significance. Seventy patients with untreated MDS [21 refractory anemia (RA), nine RA with ringed sideroblasts (RARS), 17 RA with excess of blasts (RAEB), 11 RAEB in transformation (RAEBt), and 12 chronic myelomonocytic leukemia (CMML)] were included in this study. Serum levels of sICAM, sVCAM, and IL-1beta were determined at diagnosis using commercially available immunoassays. In addition, 15 healthy volunteers were studied as a control group. sICAM, sVCAM, and IL-1beta serum levels were significantly higher in MDS patients in comparison with the control group (P <0.001). Patients with CMML showed the highest sICAM, sVCAM, and IL-1beta levels in comparison with other MDS-related subtypes. Furthermore significantly elevated levels of the studied parameters were detected in high-risk MDS patients (RAEB, RAEB-t, and CMML) in comparison with low-risk MDS (RA and RARS). IL-1beta was strongly correlated both to sICAM and sVCAM. In conclusion we have provided evidence that increased sICAM and sVCAM serum levels are related to MDS severity.
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PMID:Levels of soluble forms of ICAM and VCAM in patients with myelodysplastic syndromes and their prognostic significance. 1559 96

Thalidomide and its immunomodulatory (IMiDs) analogs (lenalidomide, Revlimid, CC-5013; CC-4047, ACTIMID) are a novel class of compounds with numerous effects on the body's immune system, some of which are thought to mediate the anticancer and anti-inflammatory results observed in humans. Thalidomide is currently being used experimentally to treat various cancers and inflammatory diseases. It is approved for the treatment of dermal reaction from leprosy and is currently in phase III trials for multiple myeloma. Thalidomide and IMiDs inhibit the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukins (IL) 1beta, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity thereby increasing the T cells' anticancer activity. They induce an IL-2-mediated primary T cell proliferation with a concomitant increase in IFN-gamma production and decrease the density of TNF-alpha-induced cell surface adhesion molecules ICAM-1, VCAM-1, and E-selectin on human umbilical vein endothelial cells. Thalidomide stimulates the Th-1 response increasing IFN-gamma levels while CC-4047 increased IL-2 as well. Some of the above immunomodulatory activities along with anti-angiogenic, anti-proliferative, and pro-apoptotic properties are thought to mediate the IMiDs' antitumor responses observed in relapsed and refractory multiple myeloma and some solid tumor cancers. This has led to their use in various oncology clinical trials. The second generation IMiD, lenalidomide, has shown potential in treating the bone marrow disorders myelodysplastic syndrome and multiple myeloma. It is currently in phase II and III trials for these diseases respectively with numerous phase II trials in other hematologic and solid tumors.
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PMID:Properties of thalidomide and its analogues: implications for anticancer therapy. 1614 35

Coagulation abnormalities are frequently reported in hemolytic anemias (HA). Several pathophysiologic mechanisms are common to different HA. In this review three different hemolytic disorders will be discussed. In sickle cell disease and in beta-thalassemia, a thrombophilic status has been well documented as multifactorial involving hemostatic changes and activation of the coagulation cascade. Moreover, in such disorders, elevated levels of endothelial adhesion protein (ICAM-1, ELAM-1, VCAM-1, von Willebrand factor, and thrombomodulin) are often increased, suggesting that endothelial activation may be involved in vascular occlusion. As an additional mechanism of hypercoagulability in thalassemia, a procoagulant status of thalassemic red cells was recognized. The main clinical manifestation of paroxysmal nocturnal hemoglobinuria (PNH) is HA, and the most common complications are thrombosis, pancytopenia, and myelodysplastic syndrome or acute leukemia. The intravascular hemolysis is explained by a deficiency of glycosil phosphatidylinositol (GPI)-anchored complement regulatory proteins such as CD59 and CD55 on the membrane of red blood cells (RBCs), but the mechanism responsible for the increased incidence of thrombotic events in PNH remains unclear. Recent advances have been made in understanding the coagulation involvement in a heterogeneous group of diseases, thrombotic microangiopathies (TMA) characterized by microangiopathic hemolytic anemia and thrombocytopenia due to platelet clumping in the microcirculation, leading to ischemic organ dysfunction with neurologic symptoms and renal impairment.
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PMID:Coagulation in the pathophysiology of hemolytic anemias. 1802 12

We studied the expression of VCAM-1 adhesion molecules on stromal cells from the bone marrow of patients with myelodysplastic syndromes, healthy donors, and patients with chronic myeloproliferative diseases and acute leukemias. Expression of adhesion molecule on mesenchymal stromal cells from the bone marrow of patients and healthy donors was evaluated after 2-4 passages by the methods of immunoprecipitation and electrophoresis. VCAM-1 expression in the majority of patients with myelodysplastic syndromes was lower than in healthy donors. At the same time, VCAM-1 expression was not identified on mesenchymal cells from acute leukemia patients. VCAM-1 expression on cells from patients with chronic myeloproliferative diseases did not differ from that in healthy donors. We conclude that VCAM-1 synthesis in bone marrow stromal cells is impaired in patients with myelodysplastic syndromes and acute leukemias. These changes can be followed by the loss of relationships between hemopoietic cells and stromal microenvironment in bone marrow niches. Hemopoietic cells gain the ability for uncontrolled growth, which results in progression of the disease.
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PMID:VCAM-1 expression on bone marrow stromal cells from patients with myelodysplastic syndromes. 2244 92