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ABSTRACT: In multiple myeloma (MM), angiogenesis plays a substantial role in disease progression. Interleukin-8 (IL-8), a pro-inflammatory chemokine with potent pro-angiogenic properties, has been implicated in the pathophysiology of MM. The aim of the study is to measure serum levels of IL-8 in MM patients and to correlate them with markers of angiogenesis, such as circulating levels of platelet derived growth factor-AB (PDGF-AB) and angiogenin (Ang), and bone marrow microvascular density (MVD). Fifty-three newly diagnosed MM patients, 23 of them, who reached plateau phase after effective treatment and 20 healthy controls, were studied. Serum levels of PDGF-AB, Ang and IL-8 were measured by ELISA, whereas bone marrow MVD was estimated by immunohistochemical staining of vessels with anti-CD31. All measured parameters were higher in MM patients compared to controls and in increased disease stages. They all also significantly decreased in plateau phase. IL-8 correlated positively with Ang and PDGF-AB, but not with MVD. The circulating levels of IL-8, PDGF-AB and Ang are elevated in patients with MM. The lack of correlation between IL-8 with MVD suggests that its levels represent the inflammatory element of MM disease and the participation in angiogenesis process is rather complex with multifactorial mechanisms.
Pathology & Oncology Research 02/2013; · 1.37 Impact Factor
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ABSTRACT: Soluble interleukin-6 receptor (sIL-6R) is part of IL-6 receptor that may stimulate cells that do not express the whole molecule. It may enhance myeloma cell proliferation and furthermore angiogenesis. The aim of the study was to evaluate the clinical significance and the relationship between serum levels of sIL-6R, with various stimulators of angiogenesis, such as hepatocyte growth factor (HGF) and interleukin-18 (IL-18) and with markers of proliferation, such as beta-2 microglobulin (B2M) levels and plasma cell Ki-67 proliferation index in the bone marrow, in patients with multiple myeloma (MM). We studied 45 newly diagnosed MM patients. Serum levels of sIL-6R, HGF, IL-18, and B2M and Ki-67 proliferation index (Ki-67 PI) in bone marrow's plasma cells were determined. The mean concentrations of sIL-6R, HGF, IL-18, and B2M and the value of Ki-67 were significantly higher in the patients compared to controls and with increasing disease stage. sIL-6R was strongly positively correlated with HGF, IL-18, B2M, and Ki-67 PI. There is a positive correlation between plasma cell growth, as determined by Ki-67 PI, and different angiogenic cytokines, such as HGF and IL-18, with sIL-6R. This relationship suggests the significant role of these cytokines in the proliferation and disease activity in MM patients.
Tumor Biology 12/2012; · 1.94 Impact Factor
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ABSTRACT: Heart failure is a very common disease, with severe morbidity and mortality, and a frequent reason of hospitalization. Anemia and a concurrent renal impairment are two major risk factors contributing to the severity of the outcome and consist of the cardio renal anemia syndrome. Anemia in heart failure is complex and multifactorial. Hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, and impaired erythropoietin production and activity are some pathophysiological mechanisms involved in anemia of the heart failure. Furthermore other concomitant causes of anemia, such as myelodysplastic syndrome and chemotherapy, may worsen the outcome. Based on the pathophysiology of cardiac anemia, there are several therapeutic options that may improve hemoglobin levels, tissues' oxygenation, and probably the outcome. These include administration of iron, erythropoiesis-stimulating agents, and blood transfusions but still the evidence provided for their use remains limited.
ISRN hematology. 01/2012; 2012:246915.
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ABSTRACT: Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and β2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM. Copyright © 2011 John Wiley & Sons, Ltd.
Hematological Oncology 09/2011; 30(3):131-6. · 2.47 Impact Factor
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ABSTRACT: Introduction. Coexistence of myeloproliferative neoplasms with lymphoproliferative syndromes has been described in the past, whereas plasma cell dyscrasias seem to be the most common cases. Case Presentation. We present a case of a 59-year-old Caucasian female of Greek origin who presented with thrombocytosis. Clinical and laboratory investigation disclosed the presence of a smoldering myeloma with coexisting histological and molecular characteristics of primary myelofibrosis. The patient had the acquired point mutation V617F in the JAK2 gene but not the bcr-abl rearrangement and was treated for myelofibrosis with subsequent improvement of all haematological parameters without evidence of myelomatic evolution. Conclusion. We present the first case in the literature of a smoldering myeloma coexisting with primary myelofibrosis. The underlying pathogenetic mechanism could be either related to the presence of a pluripotent neoplastic stem cell capable to differentiate into both lymphoid and myeloid cells or be related to two separate nosologic entities.
ISRN hematology. 01/2011; 2011:404057.
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ABSTRACT: Angiogenesis is a prerequisite for solid tumor growth, but there is relatively limited data regarding Hodgkin lymphoma. The purpose of this study was to examine the immunohistochemical expression of angiogenic and proliferation markers in Hodgkin biopsies in relation to clinical parameters. Immunostaining was performed on 65 Hodgkin biopsies with vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1alpha), platelet-derived growth factor receptor alpha (PDGFRalpha), Ki-67, and p53. Microvessel density (MVD) was determined by CD31 staining. In all cases, neoplastic cells and reactive background cells were evaluated. The neoplastic population expressed VEGF in 48% of the cases, HIF-1alpha in 54% of the cases, and PDGFRalpha in 95% of the cases. Both Ki-67 and p53 were positive in neoplastic cells in over 60% of the cases. The MVD had a median of 2.6/0.0625mm(2) which was not different from normal lymph nodes. VEGF in the non-neoplastic compartment showed increased staining in Ann Arbor stage I-II versus III-IV. In conclusion, VEGF, HIF-1alpha, and predominantly PDGFRalpha are expressed in neoplastic cells in the majority of Hodgkin lymphomas. As microvessel formation is not increased in Hodgkin, additional functions of these angiogenic molecules should be investigated.
Pathology - Research and Practice 11/2008; 205(1):11-20. · 1.21 Impact Factor
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ABSTRACT: Although tuberculosis is not uncommon among patients with myelodysplastic syndrome (MDS), only a few reports of such patients suffering from miliary tuberculosis (MT) exist. MT often presents as a fever of unknown origin and it is a curable disease, yet fatal if left untreated.
We report a case of MT with no clinical or laboratory indications of pulmonary involvement in a patient with MDS, and review the relevant literature. Mycobacterium tuberculosis was isolated from the liquid culture of a bone marrow aspirate.
Even if the initial diagnostic investigation for a fever of obscure etiology is negative, MT should not be excluded from the differential diagnosis list. Since it is a curable disease, persistent and vigorous diagnostic efforts are warranted. In suspected cases, mycobacterial blood cultures should be collected as soon as possible after hospital admission and early bone marrow aspirate with mycobacterial cultures is advocated.
Annals of Clinical Microbiology and Antimicrobials 02/2008; 7:8. · 2.64 Impact Factor
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ABSTRACT: Multiple myeloma is characterized by accumulation of plasma cells in the bone marrow, with osteolysis and increased marrow angiogenesis. We studied molecules involved in angiogenesis (MMP-9, HGF, VEGF) in relation to disease stage, extent of bone destruction, and markers of bone turnover (Ntx and PICP).
MMP-9, HGF, VEGF were measured in the serum of 42 newly diagnosed myeloma patients and 24 controls with commercial ELISA kits. Urinary levels of Ntx were measured by ELISA, and serum PICP with RIA. Extent of radiological bone disease was graded into low and high score. Stage was estimated according to the Durie-Salmon criteria.
HGF, VEGF and Ntx were higher in patients than controls (p<0.001). MMP-9 and PICP did not differ between patients and controls. HGF, VEGF, MMP-9 and Ntx increased significantly with disease stage (I to III, p<0.001) and PICP decreased significantly with advancing stage (p<0.05). There was a positive correlation between HGF and MMP-9 (r: 0.36, p<0.01), VEGF and MMP-9 (r: 0.38, p<0.01), Ntx and MMP-9 (r: 0.39, p<0.01) and an inverse correlation between PICP and MMP-9 (r: -0.66, p<0.0001).
Angiogenesis and bone destruction are closely interrelated in myeloma, and cytokine levels (MMP-9, VEGF and HGF) may be useful in monitoring progression.
Clinica Chimica Acta 05/2007; 379(1-2):31-5. · 2.54 Impact Factor
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ABSTRACT: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF). Angiogenesis is implicated in the progression of multiple myeloma (MM).
We measured serum levels of IL-17, TNF-alpha, and VEGF, as well as microvessel density (MVD) in 40 untreated MM patients.
Levels of IL-17 in the sera of patients with MM were higher than those in matched controls; however, the difference did not reach statistical significance. Serum levels of both TNF-alpha and VEGF in MM patients were significantly higher than those in controls (p<0.001 in both instances). Levels of IL-17 in MM patients, both stage II and stage III, were significantly higher than those of stage I patients (p=0.001 and p<0.001, respectively). Similarly, higher values of VEGF (p<0.001), TNF-alpha (p<0.001), and MVD (p<0.035) were associated with advanced disease stage. Serum values of IL-17 in MM patients correlated positively not only with VEGF (Spearman's rho=0.606) and TNF-alpha (r=0.552; p<0.001 in both instances), but also with MVD (r=0.385, p=0.014). In addition, a positive correlation was found between serum values of VEGF and TNF-alpha (r=0.657, p<0.001), MVD and VEGF (r=0.353, p=0.026), and between MVD and TNF-alpha (r=0.506, p=0.001) in MM patients.
These results suggest that IL-17 plays a role in the promotion of angiogenesis and associated disease progression in MM.
European Journal of Internal Medicine 10/2006; 17(6):412-6. · 2.00 Impact Factor
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ABSTRACT: Recent evidence has shown that several chemokines--including those involved in angiogenesis--have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences could be attributed to distinct angiogenic and angiostatic profiles. This hypothesis was investigated by estimating the levels of three angiogenic chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines (monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein [IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL fluid (BALF).
We studied prospectively 20 patients with sarcoidosis (median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age, 68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years; range, 26 to 60 years).
The GRO-a serum and BALF levels of IPF patients were found significantly increased in comparison with healthy subjects (799 pg/mL vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p < 0.001], respectively) and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p < 0.001] and 1,827 pg/mL vs 214 pg/mL [p < 0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in IPF patients were significantly higher compared with sarcoidosis patients (191 pg/mL vs 30 pg/mL [p < 0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03], respectively). MIG serum levels in IPF patients were found significantly upregulated in comparison with sarcoidosis patients and healthy control subjects. However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p < 0.001] and 112 pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in sarcoidosis patients compared with IPF patients.
Our data suggest distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential different role of CXC chemokines in the local immunologic response in IPF and pulmonary sarcoidosis.
Chest 10/2006; 130(4):982-8. · 5.25 Impact Factor
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ABSTRACT: Sarcoidosis, a systemic granulomatous disease of unknown etiology, is characterized by a predominantly Th1 cytokine milieu, which is involved in its immunopathogenesis. The role of novel immunologic markers reflecting T cell activity of the sarcoid immunologic response needs to be determined. The present study aims to evaluate the role of the Th1 cytokine pattern by estimating the local and systemic levels of interleukin-12 (IL-12) and IL-18 in bronchoalveolar lavage fluid (BALF), induced sputum, and serum of patients with pulmonary sarcoidosis. We studied prospectively 20 patients (12 women, 8 men) of median age 46 years (range 25-65) with sarcoidosis and 10 normal subjects (5 women, 5 men) of median age 39 years (range 26-60). IL-12 and IL-18 levels were measured using ELISA kits. The IL-12 BALF levels were significantly higher in sarcoidosis patients than in healthy subjects (5.64 +/- 0.21 pg/mL vs. 5.16 +/- 0.15 pg/mL, p < 0.001). In addition, IL-18 levels were significantly increased in BALF samples (47.69 +/- 6.29 pg/mL vs. 16.73 +/- 3.00 pg/mL, p < 0.001). A statistically significant decrease in IL-12 serum levels was detected in the sarcoid population compared with controls (5.77 +/- 0.50 pg/mL vs. 7.87 +/- 2.00 pg/mL, p < 0.001). No significant differences were detected in IL-12 and IL-18 levels between patients and controls in induced sputum samples. Our data suggest a potential role of IL-12 and IL-18 in the local immunologic response in pulmonary sarcoidosis. Further large-scale studies are needed to define the precise role of IL-12 and IL-18 in the immunopathogenesis of this disorder.
Journal of Interferon & Cytokine Research 06/2006; 26(6):400-5. · 3.06 Impact Factor
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ABSTRACT: We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation.
Journal of Autoimmunity 01/2006; 25(4):283-8. · 7.37 Impact Factor
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ABSTRACT: Interleukin-18 (IL-18) has been identified as an interferon-gamma (IFN-gamma) mediator, promoting a T helper 1 (Th1) response. Th1 response is characterized by increased expression of IFN-gamma, interleukin-12 (IL-12) and interleukin-18 (IL-18). The present study aims to evaluate the role of Th1 cytokines by monitoring changes in Induced Sputum (IS) samples, before and after treatment with IFN-gamma-1b in patients with IPF.
Fifteen patients with histologically confirmed IPF/UIP (12 male, 3 female) of median age 65 yr were prospectively studied. Ten healthy subjects (5 female, 5 male) of median age 61 yr served as control group. Patients were assigned to receive IFN-gamma-1b 200 microg (15 patients) subcutaneously three times per week for 12 months. Induced sputum (IS) IL-12 and IL-18 levels were measured before and after IFN-gamma-1b treatment in IPF patients as well as in healthy controls, using ELISA immunoassay.
The IL-18 levels were significantly higher in IPF samples before treatment than in healthy controls (57.05 +/- 6.9 pg/ml vs. 41.07 +/- 8.16 pg/ml, p < 0.05). A statistically significant decrease was detected in the IL-18 levels after IFN-gamma-1b treatment (57.05 +/- 6.9 vs. 42.8 +/- 5.1 pg/ml, p = 0.04). The IL-12 supernatant levels measured before and after IFN-gamma-1b treatment were not significantly different.
Our results may illustrate the potential role of IL-18 as an inflammatory molecule in the pathogenesis of IPF. Moreover, decrease of IL-18 levels in IPF patients, after 12 months of therapy could possibly be explained as IL-18 downregulation after IFN-gamma-1b treatment. Extended studies are needed to determine the precise role of IL-12 and IL-18 during IPF.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 10/2005; 22(3):204-9. · 1.27 Impact Factor
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ABSTRACT: Histiocytic necrotizing lymphadenitis (Kikuchi's disease, KD) is a rare benign condition of unknown origin, usually characterized by lymphadenopathy and fever, affecting mainly young women. We describe three cases of patients, one man and two women, with biopsy-proven KD detected at our university hospital during the past 3 years and we review the literature.
European Journal of Internal Medicine 10/2005; 16(5):356-8. · 2.00 Impact Factor
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) remains a relentlessly progressive lung disorder despite four decades of interest in its pathogenesis and treatment. It is important to emphasize that IPF is a progressive and irreversible illness, and, until now, there has been no available drug that has been capable of modifying the progressive natural course of IPF and its usual terminal outcome. Although the pathogenesis of this disease is complex and poorly understood, growth factors, cytokines, chemokines, and regulators of apoptosis have all been implicated in its pathogenesis and disease progression. This review summarizes the evidence implicating these molecules as primarily involved in the pathogenesis of IPF such as cytokines, chemokines and growth factors, with particular emphasis to novel interactions. The elucidation of mediators that orchestrate this aberrant tissue repair will allow the development of novel interventions to treat this devastating disorder.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 07/2005; 22(2):91-104. · 1.27 Impact Factor
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ABSTRACT: We have reported quantitative and qualitative differences in bone marrow (BM) progenitor cells in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). This study investigated the apoptotic features and cytokine suppressors of haematopoiesis in long-term cultures of BM mononuclear cells (BMMCs) from AIH-1 and PBC patients.
Apoptotic markers and CD14 expression were evaluated in 13 AIH-1 patients, 13 PBC patients, 12 cirrhotic controls and 10 healthy subjects. TNF-alpha, TGF-beta and IFN-gamma were determined using ELISAs.
All apoptotic markers and CD14 were increased in AIH-1 and PBC compared to controls (P<0.0001). Fas+ cells were positively correlated (P=0.0001) with apoptotic cells in AIH-1 and PBC. TNF-alpha and IFN-gamma were higher in AIH-1 (P=0.003 and P=0.001) and PBC (P=0.0001) compared to controls. No differences were found between the control groups.
We demonstrate for the first time that the apoptotic process, macrophage activation and the production of cytokine suppressors of haematopoiesis in BMMCs from AIH-1 and PBC patients are higher compared to controls. The Fas-FasL pathway is likely to be involved in the apoptotic process; the increased levels of selected cytokines may contribute to Fas-FasL stimulation. Cirrhosis appears unlikely to be the cause of the above findings.
Journal of Hepatology 04/2005; 42(3):393-9. · 9.26 Impact Factor
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ABSTRACT: Multiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption. Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78+/-91.27 vs. 59.25+/-33.09 ng/mL, p<0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p<0.001, p<0.03, p<0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p<0.0001, p<0.01, respectively). MMP-9 levels were lower in patients compared with controls (p<0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p<0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p<0.03, p<0.003, p<0.002, p<0.003 and p<0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation.
Clinical Chemistry and Laboratory Medicine 02/2005; 43(9):934-8. · 2.15 Impact Factor
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ABSTRACT: Angiogenesis is implicated in the progression of myelodysplastic syndromes (MDS). Bone marrow microvascular density (MVD), serum angiogenin (ANG) and interleukin 6 (IL-6) were measured in 67 patients with untreated MDS. MVD, ANG and IL-6 were significantly higher in the patient group as a whole when compared to controls (P < 0.01). MVD and ANG were significantly higher in subtypes with a high-risk for leukemic transformation (RAEB, RAEB-t and CMML) than in low-risk subtypes (RA and RARS) (P < 0.01). In the MDS group, a positive correlation was found between ANG and IL-6 (P < 0.001) and also between MVD and IL-6 (P < 0.05). Using multivariate analysis, only IL-6 displayed independent prognostic value and was inversely related to MDS survival.
Leukemia Research 01/2005; 29(1):41-6. · 2.92 Impact Factor
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ABSTRACT: The myelodysplastic syndromes (MDS) are a group of disorders characterized by dysplastic hemopoiesis and an increased risk of leukemic transformation. The process of angiogenesis has been implicated in the pathogenesis and evolution of MDS. In this study the proliferative activity and extent of angiogenesis was examined in bone marrow samples from 54 patients with MDS in relation to clinicopathologic features. Cellular proliferation and microvascular density (MVD) were examined immunohistochemically, using the monoclonal antibody MIB-1 (Ki-67) and an anti-CD34 monoclonal antibody respectively. Serum concentrations of interleukin-6 (IL-6) were measured by ELISA. The results showed that the MIB-1 Labeling Index (MIB-1 LI), MVD and IL-6 increased significantly with advancing severity of disease. Among the MDS-FAB subtypes, MIB-1 LI, MVD and IL-6 were significantly higher in RAEB-t, RAEB and CMML in comparison to RA and RARS (p < 0.0001 in all cases). Similarly, MIB-1 and MVD were increased in patients with score 3 in comparison to scores 0 and 1 in the IPSS system (p < 0.05). All parameters studied were significantly higher in patients versus controls. We conclude that cellular proliferative activity and angiogenesis are associated with disease progression in MDS patients.
Journal of Molecular Histology 12/2004; 35(8-9):857-63. · 1.48 Impact Factor
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ABSTRACT: The expression of adhesion molecules is important for the interaction of myeloma cells with the bone marrow microenvironment. In the current study, serum soluble adhesion molecules (sICAM-1 and sE-selectin) were measured in untreated multiple myeloma (MM) patients in relation with other markers of disease activity. MATERIALS and
The study group consisted of 67 patients with MM (classified according to the Durie-Salmon classification) and 15 controls. Interleukin-6 (IL-6), sICAM-1 and sE-selectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). In addition, the monoclonal protein, erythrocyte sedimentation rate (ESR) and hemoglobin (Hb) concentration were also determined.
Serum sICAM-1 level increased significantly at advanced stages of MM and was higher in comparison to controls (p<0.01). sE-selectin increased significantly with advancing stage of the disease, but did not differ from controls. IL-6, ESR and M-component were significantly higher and Hb concentrations lower with advancing stage of disease. There was a positive correlation of IL-6 with sICAM-1 and sE-selectin.
We conclude that serum sICAM-1 differs in multiple myeloma patients from normals and together with sE-selectin increase in parallel to increasing stage of disease, which may reflect a dysregulation and possible involvement of these adhesion molecules in myeloma progression.
Clinica Chimica Acta 11/2004; 349(1-2):39-43. · 2.54 Impact Factor
