Venizelion Hospital of Heraklion

Irákleion, Greece

Venizelion Hospital of Heraklion

Irákleion, Greece
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Papakonstantinou O.,Attikon Hospital | Drakonaki E.E.,University of Crete | Maris T.,University of Crete | Vasiliadou A.,Aghios Georgios Hospital of Chania | And 2 more authors.
Abdominal Imaging | Year: 2015

Purpose: Splenomegaly and splenic siderosis are well-known findings in beta-thalassemia major. We explored the relation between splenic size, splenic and hepatic siderosis in transfusion-dependent beta-thalassemic patients, assessed by MR imaging. Materials and methods: Abdominal MR imaging studies of 47 consecutive thalassemic patients and 10 healthy subjects, used as controls, were retrospectively reviewed. The signal intensity ratios of spleen and liver to the right paraspinous muscle (S/M, L/M, respectively) were calculated on T1, intermediate, and T2*-weighted gradient-echo sequences, splenic volume was estimated on axial images and serum ferritin levels were recorded. Results: Decreased S/M on all MR sequences was displayed in 36 patients. Six patients presented with normal S/M on all MR sequences and 5 patients displayed splenic hypointensity only on T2* sequence. No correlation between S/M and L/M was found whereas both L/M and S/M correlated with serum ferritin (P < 0.03). Splenic volume correlated to L/M (P < 0.05) but not to S/M values. Conclusion: In transfusion-dependent patients with beta-thalassemia, iron deposition in spleen cannot be predicted by the degree of hepatic siderosis, whereas splenomegaly relates to liver, but not splenic, iron overload. MR imaging can be a valuable tool in elucidating iron kinetics. © 2015, Springer Science+Business Media New York.


PubMed | University of Crete, Aghios Georgios Hospital of Chania, Attikon Hospital and Venizelion Hospital of Heraklion
Type: Journal Article | Journal: Abdominal imaging | Year: 2015

Splenomegaly and splenic siderosis are well-known findings in beta-thalassemia major. We explored the relation between splenic size, splenic and hepatic siderosis in transfusion-dependent beta-thalassemic patients, assessed by MR imaging.Abdominal MR imaging studies of 47 consecutive thalassemic patients and 10 healthy subjects, used as controls, were retrospectively reviewed. The signal intensity ratios of spleen and liver to the right paraspinous muscle (S/M, L/M, respectively) were calculated on T1, intermediate, and T2*-weighted gradient-echo sequences, splenic volume was estimated on axial images and serum ferritin levels were recorded.Decreased S/M on all MR sequences was displayed in 36 patients. Six patients presented with normal S/M on all MR sequences and 5 patients displayed splenic hypointensity only on T2* sequence. No correlation between S/M and L/M was found whereas both L/M and S/M correlated with serum ferritin (P<0.03). Splenic volume correlated to L/M (P<0.05) but not to S/M values.In transfusion-dependent patients with beta-thalassemia, iron deposition in spleen cannot be predicted by the degree of hepatic siderosis, whereas splenomegaly relates to liver, but not splenic, iron overload. MR imaging can be a valuable tool in elucidating iron kinetics.


Pappa C.A.,Venizelion Hospital of Heraklion | Tsirakis G.,University Hospital of Heraklion | Samiotakis P.,University of Crete | Tsigaridaki M.,University of Crete | And 4 more authors.
Cancer Investigation | Year: 2013

Angiopoietins and their receptor, Tie-2, have crucial role in angiogenesis. We measured serum levels of angiopoietin-2 (Ang-2), soluble Tie-2, and factors of burden and prognosis in myeloma (LDH, CRP, beta-2 microglobulin, and interleukin-6) in 55 newly diagnosed patients, with 30 of them in plateau phase, in order to note correlations among them. Levels of Ang-2 were higher in patients in advanced stage of disease, decreased in plateau phase, and correlated with all other factors. Circulating Ang-2 in myeloma patients significantly correlated to factors of disease burden and prognosis, and therefore measuring its levels may be important for the valuation of the disease. Copyright © 2013 Informa Healthcare USA, Inc.


Pappa C.A.,Venizelion Hospital of Heraklion | Tsirakis G.,University of Crete | Kanellou P.,University of Crete | Kaparou M.,University of Crete | And 6 more authors.
Cytokine | Year: 2011

Background: The ELR + CXC chemokines are important mediators of tumorigenesis, related to their angiogenic properties. Angiogenesis appears to be a prominent feature in the progression of multiple myeloma (MM). CXC chemokines have four highly conserved cysteine amino acid residues, with the first two cysteine molecules separated by a single amino acid. The angiogenic potential of this group is determined by the presence of three amino acid residues (Glu-Leu-Arg: the ELR motif) preceding the first cysteine amino acid, in the NH 2 terminus. Aims: The purpose of this study was to determine serum concentrations of angiogenesis-related chemokines ELR + motif, such as interleukin-8 (IL-8), epithelial neutrophil activating protein-78 (ENA-78) and growth-related gene alpha (GRO-α), as well the bone marrow microvascular density (MVD) in patients with MM at diagnosis and after treatment, in plateau phase. We also evaluated the relationship among them with other known growth factors involved in angiogenesis. Methods: Serum levels of the ELR + CXC chemokines: IL-8, ENA-78 and GRO-α as well as of the angiogenic factors: hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) were determined in 63 newly diagnosed MM patients, in 30 in plateau phase and in 20 healthy controls. Serum measurements of them were performed with commercially available kits for ELISA. Bone marrow biopsies were performed before and after treatment, in plateau phase, in order to determine MVD by staining vessels with anti-CD31. Results: Serum concentrations of IL-8, ENA-78, GRO-α and TNF-α were significantly higher in the group of MM patients (44.5 ± 25.3, 765 ± 572.1, 186.5 ± 129.1 and 4.2 ± 2.8. pg/ml, respectively) in comparison to control group (27.3 ± 6.4, 335.1 ± 268.6, 112.5 ± 76.1 and 1.3 ± 0.8. pg/ml) (p< 0.02 for GRO-α, p< 0.001 for other cases). We also found that untreated patients had higher levels of IL-8, ENA-78, GRO-α than post treatment patients, but statistical significant difference was found only for IL-8 (48.36 ± 30.93. pg/ml vs. 35.05 ± 19.77. pg/ml, p< 0.001). Furthermore IL-8, GRO-α, TNF-α, HGF and VEGF were significantly higher with increasing disease stage (p< 0.001 in all cases). ENA-78 serum levels were higher in stage III than in stage I and II, but without statistical significance. Additionally we correlated each proinflammatory cytokine with well known angiogenic factors such as HGF, VEGF and TNF-α. A positive correlation was found between serum HGF and IL-8 and GRO-α (r= 0.316 p< 0.01, r= 0.297 p< 0.02, respectively). Similarly serum VEGF correlated with ENA-78 and GRO-α (r= 0.323 p< 0.01, r= 0.469 p< 0.001, respectively). In the pretreatment group of patients a positive correlation between bone marrow MVD and serum levels of GRO-α was found (r= 0.304 p< 0.01). There was a difference in survival times between patients with higher than median versus low IL-8, ENA-78 and GRO-α levels, but the differences could not reach statistical significance in either case. Conclusions: These findings support the hypothesis that ELR + motif CXC chemokines, such as IL-8, ENA-78 and GRO-α correlate with angiogenic growth factors and may play a role in the progression of MM. Further studies are needed to determine their prognostic and predictive significance. © 2011 Elsevier Ltd.


Pappa C.,Venizelion Hospital of Heraklion | Alexandrakis M.,University Hospital of Heraklion | Boula A.,Venizelion Hospital of Heraklion | Psarakis F.,University Hospital of Heraklion | And 4 more authors.
Hematological Oncology | Year: 2013

Angiogenesis is an essential process for the expansion of multiple myeloma (MM), in which many angiogenic factors participate. Endoglin (CD105) is a transforming growth factor-β co-receptor, being mainly expressed in angiogenic endothelial cells and has been used as a marker of tumor angiogenesis, having prognostic potential. The aim of the study was to evaluate serum levels of soluble CD105 (sCD105) in MM patients, both during diagnosis and after effective conventional chemotherapy, in the plateau phase, and to correlate them with the clinical stage of the disease, as well as with the known angiogenic factors vascular endothelial growth factor, angiogenin and interleukin-18 (IL-18). Serum levels of the aforementioned factors were measured, by enzyme-linked immunosorbent assay, in 56 newly diagnosed MM patients, in 35 of them who entered plateau phase and in 24 healthy controls. Bone marrow aspirations were also performed in all patients to determine plasma cell infiltration. All measured cytokines were higher in MM patients compared with controls and with advancing disease stage (p<0.001 for all cases). Furthermore, the values of all factors decreased significantly in the plateau phase (p<0.001 for all cases). Serum levels of sCD105 correlated with the other angiogenic cytokines, whereas only serum levels of angiogenin had prognostic value for the survival. In conclusion, CD105 and the angiogenic cytokines vascular endothelial growth factor, angiogenin and IL-18, seem to have emerging roles both in angiogenesis and tumor growth in MM. © 2013 John Wiley & Sons, Ltd.


Fragioudaki M.,University Hospital of Heraklion | Tsirakis G.,University Hospital of Heraklion | Pappa C.A.,Venizelion Hospital of Heraklion | Aristeidou I.,University Hospital of Heraklion | And 5 more authors.
Leukemia Research | Year: 2012

B-cell activating factor (BAFF) is a B-cell growth factor. We measured its serum levels and correlated them with parameters of disease activity, as serum levels of tumor necrosis factor-α and lactate dehydrogenase, bone marrow microvascular density and proliferating cell nuclear antigen expression, in 50 myeloma patients, in 22 of them in plateau phase and in 20 controls. All of them were higher in patients and in advanced disease while reduced in plateau phase. BAFF correlated with all the above markers. Higher BAFF levels predicted a shorter survival, suggesting an important prognostic marker and a possible therapeutic target in myeloma. © 2012 Elsevier Ltd.


Tsirakis G.,University of Crete | Pappa C.A.,Venizelion Hospital of Heraklion | Spanoudakis M.,University of Crete | Chochlakis D.,University of Crete | And 5 more authors.
European Journal of Internal Medicine | Year: 2012

Background: Τhe importance of angiogenesis in malignancies' growth is well recognized. CD105 (Endoglin), a proliferation-associated glycoprotein, is a powerful marker of neovascularization. Elevated amounts of solubleCD105 (sCD105) have been identified in selected solid tumors. The aim of the study was to estimate circulating levels of sCD105 and soluble transforming growth factor-β 1 (sTGF-β 1), in multiple myeloma (MM) patients, to determine their significance in tumor progression and to investigate the correlation between sCD105 and markers of disease activity. Methods: We studied 50 newly diagnosed MM patients. Twenty-five of them were also investigated in plateauphase. Twenty patients with monoclonal gammopathy of undetermined significance (MGUS) were enrolled in this study. As control group 28 healthy persons were studied. We determined sCD105, sTGF-β 1 and interleukin-6 (IL-6) in the serum, Ki-67 proliferation index (Ki-67 PI) expression and microvascular density(MVD) in bone marrow with immunohistochemistry. Results: The mean concentrations of sCD105 and IL-6 were higher in MM and MGUS patients compared to controls, whereas serum levels of sTGF-β 1 were lower in MM patients compared to MGUS patients and controls. sCD105 levels, were significantly different among disease stages, with higher values in advanced stages. It was found that sCD105 correlated with Ki-67 PI, MVD and IL-6. Conclusions: CD105 seems to play an important role in angiogenesis and tumor progression. Circulating levelsof sCD105 could detect patients with more advanced disease and might help in evaluating the response to treatment. © 2012 European Federation of Internal Medicine.


Pappa C.A.,Venizelion Hospital of Heraklion | Tsirakis G.,University Hospital of Heraklion | Stavroulaki E.,Venizelion Hospital of Heraklion | Kokonozaki M.,University Hospital of Heraklion | And 3 more authors.
Cancer Investigation | Year: 2015

In multiple myeloma (MM), mast cells (MCs) modify bone marrow microenvironment. In order to estimate whether MC density (MCD) in active MM bone marrows relates to the proliferative activity of plasma cells, we estimated in 42 patients MCD, microvascular density (MVD), and the Ki-67 proliferation index (PI) (immunohistochemical expression of tryptase, CD31, and Ki-67). MCD correlated with Ki-67 PI (p < .001), suggesting the important participation of MCs in MM biology and growth; MCs enhance angiogenesis and produce cytokines with growth effects on myeloma cells. Therefore, MCs could be valuable targets for therapeutic interventions. © 2015 Informa Healthcare USA, Inc.


PubMed | Venizelion Hospital of Heraklion
Type: Journal Article | Journal: Cancer investigation | Year: 2015

In multiple myeloma (MM), mast cells (MCs) modify bone marrow microenvironment. In order to estimate whether MC density (MCD) in active MM bone marrows relates to the proliferative activity of plasma cells, we estimated in 42 patients MCD, microvascular density (MVD), and the Ki-67 proliferation index (PI) (immunohistochemical expression of tryptase, CD31, and Ki-67). MCD correlated with Ki-67 PI (p < .001), suggesting the important participation of MCs in MM biology and growth; MCs enhance angiogenesis and produce cytokines with growth effects on myeloma cells. Therefore, MCs could be valuable targets for therapeutic interventions.


PubMed | Venizelion Hospital of Heraklion, University Hospital of Heraklion and General Hospital of Chania
Type: Journal Article | Journal: Clinical therapeutics | Year: 2016

The aim of the study is to estimate whether bone marrow mast cell density (MCD) in multiple myeloma (MM) correlates with circulating levels of various angiogenic factors.In 70 patients with newly diagnosed active MM, we measured MCD using immunohistochemical stain for tryptase and serum levels of matrix metalloproteinase 9 (MMP-9), angiopoietin 2 (ANGIOP-2), and angiogenin (ANG) with ELISA.Levels of MCD, ANGIOP-2, and ANG were significantly higher in MM patients compared with the control group. The MMP-9 level was higher in MM patients compared with the control group but without statistical significance. All values were increasing in parallel with clinical stages. Furthermore, MCD correlated positively with MMP-9, ANGIOP-2, and ANG.MCs participate in the angiogenic processes of MM, with complex implicated mechanisms. This interplay between MCs and the other participants favors angiogenesis and MM growth.

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