angiogenin and Acute-Disease

The aim of study was to investigate the expression of angiogenin-2 (Ang-2) and vascular endothelial growth factor (VEGF) expression in acute leukemia (AL) and its significance in the angiogenesis and progress of AL. Serum levels of Ang-2 and VEGF in 24 de novo, 18 complete remitted (CR), 7 unremitted, 13 relapsed patients with AL were measured by enzyme-linked immunosorbent assay (ELISA), and compared with those of normal controls. The results showed that the serum levels of Ang-2 and VEGF in de novo, unremitted and relapsed patients were significantly higher than those in normal controls (p < 0.01). Compared with de novo group, the serum levels of Ang-2 and VEGF in CR patients decreased significantly, but showing no significant difference from those in normal controls (p > 0.05). In relapsed patients, the serum levels of Ang-2 and VEGF were obviously higher than those in unremitted and CR patients (p < 0.01). It is concluded that the expressions of Ang-2 and VEGF are closely related with occurrence and development of acute leukemia, the VEGF may regulate Ang-2 expression and promote angiogenesis and acute leukemia development. Preventing expressions of Ang-2 and VEGF may seem as targets for leukemia therapy in the future.

Topics: Acute Disease; Adolescent; Adult; Aged; Case-Control Studies; Child; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neovascularization, Pathologic; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Young Adult

Serum angiogenin (ANG) levels were measured with ELISA in 30 cerebral infarction patients at different time points (within 48 h and on days 3, 7 and 14 after onset of cerebral infarction) and in 20 control subjects. Serum ANG levels in patients were 415.1 +/- 76.8, 410.6 +/- 82.1, 443.6 +/- 91.1 and 395.3 +/- 83.9 ng/ml within 48 h and on days 3, 7 and 14 after cerebral infarction, respectively. Serum ANG level in control group was 334.9 +/- 93.9 ng/ml. Serum ANG levels were significantly higher in patients with cerebral infarction within 48 h and on days 3 and 7 than in the control group (p < 0.05). Serum ANG level decreased on day 14. Serum ANG levels were significantly higher in patients with large infarction than in those with moderate and small infarction at each time point (p < 0.05). Our observations that serum ANG levels increase significantly in patients with cerebral infarction and the increase in ANG levels correlates with the infarct size suggest that ANG might be involved in the pathophysiologic process of ischemic brain damage.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cerebral Infarction; Enzyme-Linked Immunosorbent Assay; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Ribonuclease, Pancreatic; Time Factors; Tomography, X-Ray Computed

Angiogenesis is a prerequisite for airway remodeling in bronchial asthma. Several factors may play important roles in inflammation and angiogenesis through effects on inflammatory cell infiltration or neovascularization.. (1) To determine the levels of vascular endothelial growth factor (VEGF) and angiogenin in sputum supernatants of asthmatic children during the acute attack and 6 weeks after start of therapy; and (2) to correlate their levels with the degree of asthma severity.. Twenty asthmatic children with acute attack (mean age, 9.6 +/- 3.5 years [+/- SD]) and 12 sex- and age-matched healthy control children were enrolled in the study. Sputum supernatants were collected for determination of VEGF and angiogenin levels. Serum samples were withdrawn for IgE measurement. The above tests were performed using an enzyme-linked immunosorbent assay. The FEV1 was measured using spirometry. VEGF, angiogenin, and FEV1 estimations were repeated for asthmatic children 6 weeks after start of therapy.. During the acute attack, asthmatic children had significantly higher levels of VEGF and angiogenin than in healthy control children (p < 0.001). VEGF and angiogenin levels showed more elevation with increase in asthma severity (p < 0.001). A significant positive correlation existed between both angiogenic factors (r = 0.98, p < 0.001). A negative significant correlation was found between FEV1 percentage of predicted and both VEGF (r = -0.99, p < 0.001) and angiogenin (r = -0.97, p < 0.001). A nonsignificant correlation was found between serum IgE and sputum VEGF (r = 0.09, p > 0.05). Although there was a significant decrease in the levels of both VEGF and angiogenin after 6 weeks of treatment with corticosteroid inhalation therapy, the levels did not reach normal control levels (p < 0.001 and p < 0.05, respectively).. Our results show that both VEGF and angiogenin levels were elevated in children with acute asthma. The study also suggests that increased severity of bronchial asthma in children is associated with the expression of both angiogenic factors, which are implicated in asthma pathogenesis. After 6 weeks of therapy, the levels of both angiogenic factors showed significant decrease.

Topics: Acute Disease; Adolescent; Angiogenesis Inducing Agents; Asthma; Child; Child, Preschool; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Ribonuclease, Pancreatic; Sputum; Vascular Endothelial Growth Factor A

Thalidomide is a putative anti-angiogenesis agent that has significant anti-tumour activity in haematological malignancies with increased bone marrow angiogenesis, including multiple myeloma (MM) and myelodysplastic syndromes (MDS). Increased levels of the mitogen for angiogenesis, vascular endothelial growth factor (VEGF), correlate with worse survival in acute myeloid leukaemia (AML). A phase II trial of thalidomide was conducted in patients with relapsed- or refractory-AML previously treated with cytarabine-containing regimens. A total of 16 patients with refractory- or relapsed-AML were treated with thalidomide 200-800 mg orally daily (median dose 400 mg daily) for a median of 27 d (range, 3-94 d). Overall, one patient (6%) achieved complete remission (CR) lasting for 36 months, and two patients had a transient reduction in marrow blasts from 8% and 7% to less than 5% in both cases. There was no correlation between reduction in levels of angiogenesis markers and response. Toxicities related to thalidomide were significant, and precluded dose escalation beyond 400 mg orally daily in most patients. Although there appears to be some evidence of biological activity, single agent thalidomide is not an optimal choice of therapy for salvaging patients with relapsed- or refractory-AML. Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti-AML therapy.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Biomarkers; Fibroblast Growth Factor 2; Hepatocyte Growth Factor; Humans; Leukemia, Myeloid; Middle Aged; Recurrence; Ribonuclease, Pancreatic; Thalidomide; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Angiogenesis is of prognostic importance not only in solid tumors but also in malignant blood diseases. We measured levels of vascular endothelial growth factor (VEGF), angiogenin (ANG), and basic fibroblast growth factor (bFGF) in peripheral blood samples from 65 patients with myelodysplastic syndrome (MDS), from 25 patients with de novo acute myeloid leukemia (AML), and from 50 healthy donors. In matched samples, VEGF levels in serum were substantially higher than VEGF levels in plasma (380.7 +/- 56 pg/ml vs. 45.3 +/- 4.5 pg/ml, mean +/- SEM, p < 0.001), whereas serum and plasma levels of ANG were comparable and significantly correlated (r = 0.8; p < 0.01). Compared to normal controls (1.3 +/- 0.09 pg), serum levels of VEGF corrected for the peripheral blood platelet count (VEGF/10(6) platelets, VEGF(PLT)) were elevated in patients with refractory anemia (RA; 3.1 +/- 0.8 pg, p < 0.01), and reached maximal values in patients with advanced stage MDS (RAEB, RAEB-t) (3.5 +/- 0.6 pg, p < 0.001), de novo AML (3.6 +/- 1.1 pg, p < 0.05), and chronic myelomonocytic leukemia (CMML; 3.7 +/- 0.9 pg; p < 0.001). Levels of soluble ANG were elevated in RA (351 +/- 25.7 ng/ml, p < 0.001), in RAEB/RAEB-t (402 +/- 17.9 ng/ml; p < 0.001), in CMML (413.8 +/- 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 +/- 17.1 ng/ml; p < 0.01, controls 255.4 +/- 8.1 ng/ml). Serum bFGF was neither elevated in MDS nor in AML patients. These results suggest that VEGF(PLT) is a marker of disease progression in MDS. Moreover, we show for the first time that elevated blood levels of ANG can be found in patients with myeloid malignancies, suggesting a role of ANG in the pathogenesis of these diseases.

Topics: Acute Disease; Case-Control Studies; Disease Progression; Endothelial Growth Factors; Female; Fibroblast Growth Factor 2; Humans; Intercellular Signaling Peptides and Proteins; Leukemia, Myeloid; Lymphokines; Male; Middle Aged; Myelodysplastic Syndromes; Neoplasm Proteins; Ribonuclease, Pancreatic; Solubility; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Nitric oxide (NO) inhibits growth and induces differentiation in acute myeloid leukaemia (AML) cells. To identify genes associated with these processes, we studied the effect of NO on AML gene expression using the technique of Representational Difference Analysis. Exposure of HL-60 cells to the NO donor DETA-NO for 24 h induced the expression of a novel gene that was named rno (regulated by nitric oxide). Treatment of HL-60 cells with dimethyl sulphoxide induced expression of rno, but treatment with Vitamin D3 or all-trans retinoic acid did not. Upregulation of rno by NO was cGMP independent. Northern blot analysis indicated that constitutive expression of the novel gene was limited to leucocytes. Three isoforms of rno were identified. An rno cDNA clone was obtained by screening a human leucocyte library. The nucleotide sequence of the open reading frame shared significant homology with that of the human ribonuclease/angiogenin inhibitor (RI). The predicted amino acid sequence indicated that, like RI, rno is leucine and cysteine rich and is comprised of a series of repetitive elements (leucine-rich repeats) that may mediate macromolecular interactions. Enhancement of expression of rno may be a component of the process by which differentiation and growth inhibition of leukaemia cells is induced by NO.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Acute Disease; Amino Acid Sequence; Base Sequence; Blotting, Northern; Enzyme Inhibitors; Gene Expression Regulation; Guanylate Cyclase; HL-60 Cells; Humans; Leukemia, Myeloid; Leukocytes; Molecular Sequence Data; Nitric Oxide Donors; Protein Isoforms; Proteins; Repetitive Sequences, Amino Acid; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease, Pancreatic; Sequence Homology, Nucleic Acid; Sulfuric Acid Esters; Triazenes

Human angiogenin is a potent inducer of angiogenesis. The association between angiogenin and cancer progression and poor outcome in solid tumours has been documented, but its significance in leukaemias has not been evaluated. We evaluated plasma angiogenin levels in 101 previously untreated patients with acute myeloid leukaemia (AML) (59 patients) and advanced myelodysplastic syndrome (MDS) (42 patients). Angiogenin levels were significantly higher in AML and advanced MDS patients than in healthy individuals (P < 0.00001). Angiogenin levels were also significantly higher in advanced MDS than in AML (P = 0.001). Higher levels of angiogenin correlated with prolonged survival periods in both AML and advanced MDS patients (P = 0.02 and 0.01 respectively). We found no correlation between angiogenin plasma level and various patient characteristics, including age, performance status, antecedent haematological disorder, haemoglobin, white blood cell and platelet counts, and poor prognosis cytogenetics. There was no significant correlation between angiogenin level and complete remission rate and duration in AML or advanced MDS patients. In multivariate analysis, angiogenin concentration retained its significance as a prognostic factor in AML (P = 0.03), together with age (P = 0.00007) and haemoglobin (P = 0.03).

Topics: Acute Disease; Biomarkers; Case-Control Studies; Disease Progression; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Humans; Leukemia, Myeloid; Middle Aged; Multivariate Analysis; Myelodysplastic Syndromes; Ribonuclease, Pancreatic; Survival Rate

Neutrophils play a key role in the physiopathogenesis of acute lung injury in general and acute respiratory distress syndrome (ARDS) in particular. To identify the anti-inflammatory mediators with a protective effect on lung tissue damage in ARDS, we correlated the concentration of the Clara cell 16-kD protein (CC16; an inhibitor of neutrophil chemotaxis), angiogenin (an inhibitor of degranulation), and the total radical oxygen neutralizing activity with the amount of elastase (a marker of neutrophil activation) and with the Pao2/Fio2 ratio, which is inversely related to lung injury.. University hospital.. Patients with ARDS (n = 12) and patients at risk for developing ARDS (n = 14).. Patients underwent bronchoalveolar lavage 12 hrs after diagnosis of ARDS or at-risk status.. The amount of CC16 and radical oxygen neutralizing activity was not significantly different in patients with or at risk for ARDS. In contrast, the amount (mean +/- sem) of angiogenin in the bronchoalveolar lavage of ARDS patients (45 +/- 14 ng/mL, n = 12) was increased 11-fold (p <.05) compared with patients at risk for ARDS (4 +/- 1 ng/mL, n = 14). In patients with ARDS, the amount of protein and angiogenin in bronchoalveolar lavage increased with decreasing concentration of CC16 (p <.05). In addition, CC16 correlated with the Pao2/Fio2 ratio (p <.05) and inversely with the amount of elastase (p <.05) and thus may be regarded as a reliable protective agent for lung injury.. A high concentration of CC16, a natural inhibitor of neutrophil function, decreases neutrophil-mediated lung damage of patients with ARDS. Strategies to increase natural anti-inflammatory agents, and thus influence the disruption of the balance between natural inflammatory and anti-inflammatory or protective factors, could be useful to modulate the tissue destruction and the course of ARDS.

Topics: Acute Disease; Adult; Aged; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Endopeptidases; Enzyme Inhibitors; Female; Humans; Inflammation Mediators; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Prognosis; Prospective Studies; Proteins; Respiratory Distress Syndrome; Ribonuclease, Pancreatic; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Uteroglobin

Topics: Acute Disease; Adult; Biomarkers; Bronchoalveolar Lavage Fluid; Female; Humans; Inflammation Mediators; Male; Neutrophils; Prognosis; Proteins; Respiratory Distress Syndrome; Ribonuclease, Pancreatic; Sensitivity and Specificity; Up-Regulation; Uteroglobin