ALBERT

Description: BACKGROUND: Angiogenesis and activation of coagulation system in cancer patients are common and are thought to be unfavorable clinical parameters. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) are well-known angiogenic cytokines. The elevations of plasma fibrinogen and D-dimer level indicate coagulation and fibrinolysis activation. There may be links between angiogenic cytokines and coagulation - fibrinolysis factors in cancer. Possible specific interactions include releasing angiogenic factors, such as VEGF by activated platelets and binding of VEGF and bFGF to fibrin and fibrinogen resulting in an increase in endothelial cell proliferation. AIM: The purpose of our study was: (a) to analyze relations of VEGF, bFGF serum levels and fibrinogen, D-dimer plasma levels with stage of disease according to Ann Arbor Staging System (AASS); (b) to evaluate correlation between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in non Hodgkin’s lymphoma patients. MATERIAL AND METHODS: 52 non Hodgkin’s lymphoma patients (31 men, 21 women; median age 52,1 ± 14,7 years) in II, III or IV stage of disease according to AASS were assessed. In stage II were 15, in stage III- 10 and in stage IV- 27 persons. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined using Behring Coagulation System (BCS) equipment. RESULTS: Plasma level of D-dimer was elevated in majority of patients, mean plasma D-dimer levels [ng/ml] were in stage II: 1654,3 ± 1301,5, in stage III: 1816,6 ± 1370,7, in stage IV: 2747,1 ± 1410,8. There was significantly higher D-dimer level in IV stage of disease in comparison to stage II and III. p

Description: Background: Despite improvements achieving complete remission and progress in supportive care of children with acute leukemias or solid tumors during the last decade, there are no optimal prognostic markers in stratification of risk of adverse events leading to poor outcome. The endogenous nitric oxide synthesis inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality. Aim: To investigate the clinical significance of methylarginines in leukemia and solid tumors in children. Material and method: Concentration of metabolites of nitric-oxide pathway in children during therapy of acute leukemia (ALL) – N 12 and solid tumors N 15 (osteosarcoma, RMS, PNET, Wilms’ tumor) was determined. Correlations of biochemical markers, blood count parameters and plasma level of methylarginines were investigated. In addition, the influence of cytostatics on NO-pathway metabolites was analyzed. Results: Table 1: Differences in mean plasma concentration of arginine, ADMA and SDMA in pts with leukemia vs pts with solid tumor Leukemia N=12 Mean ±SD Median±SEM Solid tumor N=15 Mean ±SD Median±SEM p Arg 31,28±8,63 30,82±2,49 49,59±10,81 49,18±3,00 0,0003 ADMA 1,17±1,10 0,53±0,32 0,98±1,10 0,46±0,31 NS SDMA 1,18±1,10 0,80±0,32 1,56±1,02 1,09±0,28 NS Arg/ADMA 67,40±54,31 69,48±15,68 228,82±451,44 117,35±125,21 NS Table.2. Differences in mean plasma concentrations of arginine, ADMA and SDMA depending on gender, treatment, etc. N=27 Arginine ADMA SDMA Arg/ADMA Sex 1. Mail; 2. Femail 1. 0.NS NS NS NS HSCT (1-yes; 0-no) 1. 0.NS NS NS NS Remission (1-yes; 0-no) 1. 0.NS NS NS NS Currently infection (1-yes; 0-no) 1. 0.NS NS NS NS Glucocoricoids (1-yes; 0-no) 1. 31,9±9,30. 51,0±11,2 p=0,0011 NS NS NS Cytostatic – any (1-yes; 0-no) 1. 0. NS NS NS NS Doxorubicine (1-yes; 0-no) 1. 0. NS NS NS NS Vincristine (1-yes; 0-no) 1. 0. NS NS NS NS Cytarabine (1-yes; 0-no) 1. 32,0±10,50. 45,6±10,8 p=0,022 NS NS NS Methotrexate (1-yes; 0-no) 1.0 NS NS NS NS Thioguanine/6-merkaptopurine(1-yes; 0-no) 1. 0. NS NS NS NS Cyclophosphamide/Iphosphamide(1-yes; 0-no) 1. 0. NS NS NS NS Conclusions: Plasma level of L-Arg was significantly higher in patients with solid tumor The L-Arg/ADMA ratio was not significantly higher in patients with solid tumors and lower plasma level of ADMA was found. Treatment with glucocorticoids and cytarabine was associated with significantly lower level of L-Arg. No significant treatment dependent difference was found in level of nitric oxide metabolic pathway.

Description: Background: Neoplasms in children are uncommon diseases however they have broad impact on the society. Despite novel therapeutic strategies for children suffering from leukemia or solid tumor, the mortality rate of the disease is still high. The endogenous nitric oxide synthesis inhibitor asymmetrical dimethyl-L-arginine (ADMA) is considered to be a strong cardirovascular risk factor and may lead to new therapeutic strategies. Our previous findings indicate that elevated plasma level of ADMA is correlated with worse prognosis in adult patients with NHL. There are no data available pointing at metabolites of NO-pathway nor clinical evidence as prognostic factor of oncological treatment in children. Aim: To investigate the relation between elevated plasma level of NO-pathway metabolites and well established markers of clinical stage of the disease. Material and method: 12 children with acute leukemias (ALL, AML), 13 with solid tumor (PNET, osteosarcoma, Wilms’ tumor, RMS) during hemato-oncological treatment were recruited to a pilot study and N=15 healthy children to a control group. Plasma concentrations of ADMA, SDMA, L-Arg was determined. Relationship to clinical stage of the disease, biochemical and blood markers was tested. Results Table 1: Differences in mean plasma concentrations of arginine, ADMA and SDMA in pts with leukemia vs pts with solid tumor vs control group Control:N=15 Mean ±SD Median ±SEM Leukemia;N=12 Mean±SD Median ±SEM Solid tumour; N=13 Mean±SD Median ±SEM P L-Arg 68,58±24,29 60,19±6,27 31,28±8,63 30,82±2,49 49,59±10,81 49,18±3,00 0,0000 ADMA 0,62±0,10 0,61±0,02 1,17±1,10 0,53±0,32 0,98±1,10 0,46±0,31 NS SDMA 0,44±0,18 0,39±0,04 1,18±1,10 0,80±0,32 1,56±1,02 1,09±0,28 0,0024 ARG/ADMA 112,8±46,28 107,4±11,94 67,40±54,31 69,48±15,68 228,82±451,44 117,35±125,21 NS Table 2:Significant correlations in group of pts with solid tumor and in patients with leukemia LEUKEMIA; N=12 R p ADMA & Ca 0,78 0,008 SDMA & Ca 0,75 0,011 SDMA & CRP −0,78 0,021 Arg/ADMA & K −0,72 0,019 Arg/ADMA & Ca −0,64 0,043 Arg& MONOCYTE 0,65 0,043 ADMA & TOT.BILIRUB. −0,92 0,000 ADMA & TOT.PROTEIN 0,75 0,032 SDMA & EOSINOPHILE 0,73 0,025 SDMA & TOT.BILIRUB −0,82 0,007 Arg/ADMA & TOT.BILIRUB. 0,81 0,009 SOLID TUMOR; N=15 R p Arg &RBC 0,70 0,016 Arg & Hb 0,64 0,035 Arg & LYMPHOCYTE 0,81 0,003 Arg & EOSINOPHILE 0,76 0,011 ADMA &MONOCYTE −0,78 0,008 ADMA & TOT.PROTEIN 0,62 0,040 ADMA & Hb 0,64 0,035 Arg/ADMA &MONOCYTE 0,82 0,004 Arg/ADMA & BASOPHILE 0,65 0,043 Conclusions:A lower plasma level of L-Arg was found both in pts with leukemia and solid tumors. Higher plasma concentration of SDMA was found in patients with leukemia and solid tumor compared to the control group. Further studies are necessary to clarify the significance of these findings.

Description: BACKGROUND: Corticosteroids are still a cornerstone in multiple myeloma (MM) therapy, both as a single agent and as a part of many protocols, including VAD regimen (vincristine, adriblastine, dexamethasone). Corticosteroids are known to be involved in blood pressure (BP) regulation and to affect this parameter. The impact of dexamethasone (Dex) administration on BP in MM patients during VAD protocol treatment is poorly documented. AIM: The purpose of the study was to evaluate the blood pressure changes during Dex administration in patients treated with VAD protocol due to MM. METHODS: Thirteen patients with MM (7 men and 6 women; mean age 62,45 ± 8,14) were assessed. Primary hypertensive patients (7 persons) were not excluded. They were administered Dex in standard dose of 40 mg (day 1–4, 9–12, 17–21) according to VAD protocol. Blood pressure was assessed by the use of commercially available instruments of Ambulatory Blood Pressure Monitoring (ABPM). The BP recordings lasted 48 hours, were started on the day before the first day of VAD and were obtained every 10 minutes during mornings, every 15 minutes during the rest of days and every 20 minutes during nights. Average of systolic and diastolic blood pressure (SBP/DBP) were estimated for the 2-hour time before Dex and for the 14-hour time in the 2-hour periods after Dex. Minimal and maximal range of SBP/DBP increase and the mean amount of SBP/DBP increase were also determined. RESULTS: 48-hour BP recordings revealed a significant increase in systolic and diastolic blood pressure after Dex administration in all patients. SBP and DBP began to increase after 3 hours after Dex, then rose continually and reached the peak in the period from 6 to 10 hour after Dex. In comparison to 2-hour period before Dex, in which SBP/DBP amounted 139,63/82,92 ± 23,47/9,38 mmHg, the mean SBP/DBP increase rate was: in the 2–4 hour period after Dex - 146,68/88,15 ± 24,38/10,51 mmHg (p