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)

Human urinary macrophage colony-stimulating factor (hM-CSF) is a glycoprotein with a molecular weight of 85 kDa which consists of two homologous subunits with a molecular weight of 43 kDa. It stimulates monocyte production through the stimulation of progenitor cells to differentiate to mature monocytes as well as neutrophil production through the stimulation of mature monocytes to produce granulocyte-macrophage and granulocyte CSF. It also enhances platelet production through the production of megakaryocyte potentiator (Meg-POT). Recently, proteoglycan type M-CSF has been found by our group. This type of M-CSF has a molecular weight of greater than 200 kDa and consists of a 43 kDa subunit and a 150-200 kDa subunit, the latter of which contains chondroitin sulfate glycosaminoglycan. This proteoglycan type M-CSF binds to extra-cellular matrix at the part of glycosaminoglycan. In addition to hematopoiesis-stimulating activity, M-CSF has a promoting activity on monocyte tumor-killing, osteoclast production and differentiation of cytotrophoblasts to syncytiotrophoblasts which secrete gonadotropin. M-CSF receptor (M-CSF-R) was found as a product of proto-oncogene, c-fms which consists of 972 amino acids. Mutations at Tyr 969 and Ser 301 of M-CSF-R has been found in patients with myelodysplastic syndrome and monocytic leukemia.
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PMID:[Function,molecular structure and gene expression of macrophage colony-stimulating factor]. 143 77

To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108 micrograms glycoprotein (group I) or 216 micrograms glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (greater than 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p = 0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.
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PMID:A randomized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia. EORTC Leukemia Cooperative Group. 158 5

A patient with acute myelomegakaryocytic leukemia (AMMgL), which developed from myelodysplastic syndrome (MDS) after chemotherapy against complicated small cell lung cancer, is reported. The patient was a 66 year-old male, who first presented with moderate macrocytic anemia. Bone marrow aspiration showed absolute erythroid hypoplasia and morphological abnormalities were found in erythroid, granuloid and megakaryocytic lineage cells. Iron utilization studies using radioisotope showed ineffective hematopoiesis. He was diagnosed as having MDS (refractory anemia) and treated with prednisolone, fluoxymesterone, and transfusions. After 3 years, small cell lung cancer was found, but he achieved complete remission with chemotherapy. Since then, pancytopenia progressed with myelofibrosis. Abnormal blasts were found in peripheral blood and gradually increased. He finally died from a blastic crisis resulting in gastric bleeding. The blasts were peroxidase negative, platelet peroxidase positive (10%), and glycoprotein II b/III a antibody positive, indicating megakaryoblasts.
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PMID:[Acute myelomegakaryocytic leukemia developed from myelodysplastic syndrome after chemotherapy against complicated small cell lung cancer]. 164 8

Recombinant granulocyte colony-stimulating factor (rG-CSF) is a glycoprotein hormone which has been produced in mammalian cells and, in a nonglycosylated form, in the bacterium Escherichia coli through recombinant DNA technology. It stimulates proliferation, differentiation and activation of cells of the neutrophil-granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions, both iatrogenic and disease related. rG-CSF is well tolerated, the most frequently reported adverse effect being mild to moderate bone pain. A major use for rG-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. rG-CSF accelerates neutrophil recovery after chemotherapy, leading to a reduction in duration of the neutropenic phase. Consequently, infection rate is diminished, as is the associated usage of antibiotics and duration of hospitalisation. The implications are that rG-CSF may allow increased dose intensity and stricter adherence to chemotherapy schedules. The increase in neutrophils produced by rG-CSF renders it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias for which current therapy is not very successful. rG-CSF may be an effective therapy in myelodysplasia, although there is concern about acceleration of the possible rate of conversion of this disease to acute myelogenous leukaemia. It is also likely that rG-CSF will be useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumour. Furthermore, there is great potential for expansion of the role of rG-CSF as monotherapy or in combination regimens with other cell factors in various haematological disorders such as aplastic anaemia. In summary, while many aspects of its use remain to be clarified, rG-CSF must be seen as an exciting advance in therapeutics. It should rapidly find an important place as an adjunct to cancer chemotherapy, and also appears to have substantial potential in a number of other neutropenic conditions which are currently difficult to treat.
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PMID:Recombinant granulocyte colony-stimulating factor (rG-CSF). A review of its pharmacological properties and prospective role in neutropenic conditions. 171 26

Radiation leukemia virus (RadLV)-induced preleukemic (PL) latency is characterized by the appearance of virus-infected PL cells in the thymus. The survival of these PL cells is dependent upon autostimulation with interleukin 4 (IL-4). We have intervened prophylactically in RadLV-induced preleukemia by using cyclosporin-A (CSA), which inhibits IL-4 production, and an immunotoxin (ITx) that kills PL cells. CSA efficiently inhibited IL-4 secretion from RadLV-induced PL and leukemic cells, and its administration to PL mice caused a significant delay in their death. An ITx consisting of anti-RadLV glycoprotein-70 (gp70) antibody coupled to ricin A chain efficiently inhibited protein synthesis in virus-infected cells in vitro and, when injected into PL mice, also delayed their death. Combined treatment with CSA and ITx prevented 75% of the treated PL mice from developing lymphoma. These results show that the development of malignancy from a premalignant state can be averted by a combination of therapeutic modalities that decrease the size and growth rate of the premalignant cell population.
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PMID:Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin. 173 46

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66

Hematological disorders are commonly complicated by anemia, and the symptoms of red cell deficiency adversely affect the quality of life. Erythropoietin is a glycoprotein which controls red blood cell production. Recombinant human erythropoietin, 50 U/kg/day, was given subcutaneously to 16 patients with myelodysplastic syndrome and anemia. All but one patient was transfusion dependent. Diverse pretreatment endogenous serum erythropoietin levels were noted and ranged from 17 to 3616 IU/l. Two patients (12.5%) demonstrated an improvement in hemoglobin levels obviating the need for transfusions. Their responses lasted 5+ and 7 months with maintenance erythropoietin treatment. The responders had endogenous serum erythropoietin levels of 44 and 170, respectively. Treatment was generally tolerated without constitutional side-effects. However, three patients developed thrombocytopenia and one developed joint pain and leukocytosis on treatment. Overall, six patients showed changes in non-erythroid cells: two patients had an increase in platelet counts; three patients, a decrease in platelet counts; and one patient, an increase in white blood cell counts. Most of these changes reversed rapidly once erythropoietin was stopped. It is concluded that (a) serum erythropoietin levels are extremely variable in anemia patients with myelodysplastic syndrome, (b) only a minority of patients benefit from treatment with recombinant human erythropoietin, and (c) erythropoietin can affect cells of the myeloid and megakaryocytic lineage in a small proportion of patients.
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PMID:Erythropoietin treatment in patients with myelodysplastic syndrome and anemia. 196 Oct 41

Interleukin-3 (IL-3) is a glycoprotein belonging to the hematopoietic growth factor family that in preclinical in vitro and in vivo studies has exhibited a multilineage activity. Phase I/II trials with recombinant human IL-3 (rhIL-3) expressed in yeast are being done in patients with advanced malignancies as well as in patients with bone marrow failure states. Subcutaneous administration of rhIL-3 at dosages between 30 and 500 micrograms/m2 for 15 consecutive days has resulted in a dose-dependent increase in platelet counts as well as in a substantial increase in the number of circulating neutrophils, eosinophils, monocytes, and lymphocytes in patients with advanced malignancies but normal hematopoiesis. Erythropoiesis is less stimulated with an increase in hemoglobin concentration only in a minority of patients. In patients with secondary hematopoietic failure due to prolonged chemo-/radiotherapy or bone marrow infiltration by tumor cells, treatment with rhIL-3 leads to a clinically significant restoration of hematopoiesis, especially of thrombopoiesis and granulopoiesis. rhIL-3 has also been shown to improve neutrophil and platelet counts in patients with myelodysplastic syndromes, while improvement of hematopoiesis is rarely observed in patients with severe aplastic anemia with the presently used treatment schedules. Adverse effects of rhIL-3 are minor at the clinically used dosages and include fever, bone pain, headache, and stiffness of the neck. Transient thrombocytopenia has been observed in a few patients with myelodysplastic syndrome or aplastic anemia treated at dosages of 250-500 micrograms/m2. rhIL-3 is a multilineage hematopoietic cytokine with promising effects on platelet and neutrophil counts and special usefulness in patients with secondary hematopoietic failure.
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PMID:Clinical effects of recombinant human interleukin-3. 204 66

The colony-stimulating factors (CSF) are a class of glycoprotein hormones that regulate the production and function of blood cells. Human sequences encoding four of the factors active on myeloid cells--granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3)--have been molecularly cloned and the biosynthetic (recombinant) products introduced into clinical trials. Sufficient clinical data have accumulated regarding G-CSF and GM-CSF to allow insight into their potential use in clinical practice. Both molecules have shown some impact in the prevention of chemotherapy-induced neutropenia and in the treatment of cytopenias associated with myelodysplastic syndromes and aplastic anemia. G-CSF has shown promise in the treatment of congenital and idiopathic neutropenias.
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PMID:The colony-stimulating factors: biology and clinical use. 214 19

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 10 patients with refractory malignancies, 2 patients who had myelodysplastic syndromes with severe neutropenia and to a patient who had delayed marrow recovery after 3 cycles of therapy for acute leukemia. A marked neutropenia and monocytopenia was observed within 5 min after an i.v. injection of GM-CSF. This persisted for 1-2 h and seemed related to activation of an adhesive glycoprotein (MO1) on the surface of these cells. With continued daily i.v. administration of GM-CSF, all patients with refractory malignancies developed a striking leukocytosis. Total leukocyte counts reached 75,000/microliters within 2 weeks of treatment. This was due to an increase in band and segmented neutrophils, eosinophils and monocytes. Accelerated myelopoiesis required the continuous presence of GM-CSF; with pump failure for 24 h or discontinuation after 14 days, leukocyte counts returned to normal levels in 24-48 h. GM-CSF also increased myelopoiesis in the patients with myelodysplastic syndromes or following anti-leukemic treatment. These observations suggest that this growth factor should prove a useful adjunct in the treatment of patients with malignancies and bone marrow failure.
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PMID:Use of granulocyte-macrophage colony-stimulating factor in patients with malignancy and bone marrow failure. 218 42


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