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  • 1
    In: Clinical Leukemia, Elsevier BV, Vol. 1, No. 3 ( 2007-3), p. 195-197
    Type of Medium: Online Resource
    ISSN: 1931-6925
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2007
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  • 2
    In: Hematological Oncology, Wiley, ( 2009), p. n/a-n/a
    Type of Medium: Online Resource
    ISSN: 0278-0232 , 1099-1069
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 2001443-0
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  • 3
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2284-2284
    Abstract: Buerger’s disease or thrombangiitis obliterans (TAO) is non artherosclerotic vascular disease that most commonly affects the small and medium-sized peripheral arteries and veins. Although a strong association with tobacco use has been established, the cause of the disease remains unknown. Possible pathogenic factors include autoimmune phenomena, haemostatic factors abnormalities and hyperhomocystynemia, however their role still remains controversial. In this study we investigated the role of blood coagulation and fibrinolytic factors abnormalities in the development of TAO. We assessed plasma activity of factor VII (FVII) factor VIII (FVIII), factor IX (FIX), plasminogen (PLG), urokinase type plasminogen activator (uPA) and its receptor (uPAR), uPA complex with plasminogen activator inhibitor 1 (uPA-PAI-1), anexin V, apolipoprotein A (ApoA), homocysteine, folic acid and serum lipids profile. Blood samples were collected from 37 patients with TAO (8 female and 29 male) with median age 39.5 years (ranging from 20 to 50 years). In patients with Buerger’s disease there were significantly higher levels of prothrombotic factors as compared to healthy control: anexin V (8.27±6.28 ng/ml vs 2.93±2.06 ng/ml, p=0.0003), FIX (109.72±30.05% vs 78.54±12.28%, p=0.000003), FVII (123.28±30.10% vs 104.36±43.38%, p=0.0001), FVIII (119.85±44.39% vs 60.19±20.77%, p=0.0000001), homocysteine (11.53±2.88 μmol/l vs 9.86±2.20 μmol/l, p=0.01) and fibrinogen (5.06±1.94mg/dL vs 3.31±1.03mg/dL, p=0.00007). Mean uPA, uPAR and uPA/PAI-1 complex plasma levels were also higher in patients with Buerger’s disease than in healthy control: 1067.07±264.97pg/mL vs 979.01±170.93pg/mL, p=0.0008; 1798.22±438.43pg/mL vs 1348.20±194.95pg/mL, p=0.000004; 303.60±288.16pg/mL vs 110.17±166.71pg/mL, p=0.000006, respectively. In contrast, plasma concentrations of ApoA and folic acid were significantly lower in patients with TAO compared to healthy control: 135.30±18.77pg/dL vs 156.46±19.97pg/dL, p=0.004 and 4.82±2.35mg/dL vs 6.84±2.70mg/dL, p=0.0006; res. Moreover there was a significant correlation between prothrombotic factors plasma levels: FIX and plasminogen (R=0.44) as well as between FVII and uPA-PAI complex (R=0.52). We found significant differences concerning studied parameters between smoking and non-smoking patients with TAO: i.e. significantly higher level of PLG (120.66±14.33pg/mL vs 108.07±17.97pg/mL, p=0.03), total cholesterol (198.36±43.95mg/dL vs 178.64±44.93mg/dL, p=0.001) and triglycerides (161.36±117.47mg/dL vs 103.50±63.20mg/dL, p=0.04), as well as lower plasma levels of folic acid (4.43±2.31mg/dL vs 5.59±2.39mg/dL, p=0.02) in smokers group. Coffee use correlated only with increased homocysteine plasma level (12.31±2.70 vs 9.96±2.68, p=0.04). In 72.2% of TAO patients, surgery was required due to aggressive disease. In this group, we found higher level of plasminogen (119.78±15.34pg/mL vs 105.12±16.35pg/mL, p= 0.04), FVII (128.50±28.90% vs 109.70±30.70%, p=0.03), total lipids (692.49±186,33mg/dL vs 514.00±96.30mg/dL, p=0,002), cholesterol 201.73±42.63mg/dL vs 162.00±38.46mg/dL, p=0.02) and triglycerides (163.62±110.70mg/dL vs 74.50±27.09mg/dL, p=0.001) as compared to the patients treated only conservatively. Our results indicate an important role of hemostatic risk factors in pathogenesis of Buerger’s disease with special regard to increased plasma concentration of homocysteine that was proved to cause lesions of blood vessels endothelium. Decreased serum level of folic acid that was found in TAO patients may contribute to hyperhomocysteinemia. Patients with aggressive clinical course of TAO, requiring surgical treatment had more disturbances in serum lipids. These findings suggest that diet supplementation of folic acid as well as normalization of lipids balance might influence clinical course of TAO.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 4
    In: Acta Haematologica, S. Karger AG, Vol. 119, No. 3 ( 2008), p. 187-189
    Type of Medium: Online Resource
    ISSN: 0001-5792 , 1421-9662
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2008
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    detail.hit.zdb_id: 80008-9
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  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 1567-1567
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 1567-1567
    Abstract: In the recent years the treatment of patients with multiple myeloma (MM) has changed because of the introduction of new agents, mainly thalidomide (THAL) and its derivatives and bortezomib, an inhibitor of the 20S proteasome. Lovastatin (LOV) and other inhibitors of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, have been demonstrated to exibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines including our own experiments. This observation induced us to administer LOV in combination with THAL and dexamethasone (DEX). We report here our preliminary experiences with THAL and LOV therapy in patients with refractory and relapsed MM. We have treated 81 patients with THAL+DEX regimen (TD) or THAL+DEX+LOV regimen (TLD). Patients received drugs orally in 28 day cycles. THAL was given from day 1 to day 28 each cycle and it was started at a initial dose of 100 mg daily increased to 300 mg daily. DEX was administered at a dose of 40 mg daily in days 1–4 each cycle. LOV was administered at a dose of 2 mg/kg in days 1–5 and 8–12 and at a dose of 0.5 mg/kg in days 15–28 each cycle. TLD regimen was administered to 43 patients and TD regimen to 38 patients. Patients characteristics before treatment were as follows: the median age 61.2 years; 61% of patients IgG, 26% IgA, 7% light chain and 6% other; 76% of patients were light chain kappa and 24% lambda; median serum M-protein level was 4.2 g/dl, bone marrow plasma cells 47%, hemoglobin 10.1 g/dl, platelets 197 G/l, beta-2-microglobulin 4.2 mg/ml, albumin 3.9 g/dl and LDH 292 IU. The median follow-up was 29 month. A clinical response, defined as a reduction of M-protein level by 50% or more, was observed in 67.8% of patients in TD group and in 88.0% in TLD group. CR i NCR was observed in 35.0% and 62.7% respectively. In 11 TLD (25.5%.) and 4 TD (10.5%) patients successful stem cell harvest was performed and mean amount of collected CD34+ cells was 8.2*106/kg. Successful autologous transplantation was performed in 8 patients from this group. Overall survival in TLD group (median 23.0 months) was significantly longer than in TD group (median 18.0 months). Similarly event free survival was longer in TLD (median 7.0 months) group than in TD group (4.5 months). We observed significant negative correlation between response and bone marrow infiltration (p=0.008), M-protein level (p=0.0004) and positive correlation between response and albumin level (p=0.005). Short time to reduction of M-protein by 50% was connected with better response. Common side effects as somnolence, fatigue and constipation were observed in about 45% of patients in TLD and TD groups. In 2 TLD and in 3 TD patients we diagnosed deep vein thrombosis. In 2 TLD patients sinus bradycardia was observed. Our results suggest that addition of LOV to THAL and DEX improves response rate in patients with refactory and relapsed MM. Moreover it is possible to harvest stem cells and perform autologous stem cells graft in patients treated with such regimen. A future prospective randomised study is needed to confirm the value of LOV or other HMG-CoA reductase inhibitors in the treatment of MM patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5120-5120
    Abstract: Proteins belonging to the TNF-family, i.e. Fas ligand (FasL), Fas, TRAIL, TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), are involved in the pathogenesis of anaemia in multiple myeloma patients. Thalidomide (THAL) is successfully used in the treatment of multiple myeloma (MM) and response is usually accompanied by an increase in haemoglobin concentration. In our previous study comprising 234 MM patients treated with THAL we observed that in the group of non-responders more than 50% of patients had improved hemoglobin level after 3 months of treatment. In the present study 29 patients with refractory/relapsed MM were treated with THAL in an initial dose of 100 mg daily, increased to 400 mg. We measured the expression of the erythropoietin receptor (EPOR) and proteins belonging to the TNF-family on erythroblasts as well as the expression of the TNF-family proteins on monoclonal plasmocytes using flow cytometry before and after 3 months of treatment. Erythroblasts and plasma cells were also investigated in short-term cultures of bone marrow mononuclear cells of MM patients. A clinical response was observed in 17 patients (58.6%), but haemoglobin concentration increased in 20 patients (75.9%). An increase in haemoglobin concentration was observed in 12 patients responding to THAL and in 10 patients not responding. The expression of FasL, Fas, TRAIL and TRAIL-R1 decreased significantly during THAL treatment, whereas the expression of EPOR and TRAIL-R2 did not change significantly. In vitro studies revealed that the expression of FasL, TRAIL, TRAIL-R1 and TRAIL-R2 was lower in THAL cultures than in control cultures. The expressions of TNF-like receptors/ligands on monoclonal plasmocytes did not differ significantly between cultures with and without THAL. Altogether our results suggest that THAL may stimulate erythropoiesis and increase haemoglobin level in MM patients and the way in which THAL acts may be connected with a decrease in the expression of TNF-like ligands/receptors on erythroblasts.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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