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Levidou G.,National and Kapodistrian University of Athens | Sachanas S.,Athens Medical Center Psychicon Branch | Pangalis G.A.,Athens Medical Center Psychicon Branch | Kalpadakis C.,University of Crete | And 17 more authors.
BioMed Research International | Year: 2014

A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in ∼40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereasIL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients. © 2014 Georgia Levidou et al.


Sachanas S.,Athens Medical Center Psychicon Branch | Pangalis G.A.,Athens Medical Center Psychicon Branch | Kalpadakis C.,University of Crete | Yiakoumis X.,Athens Medical Center Psychicon Branch | And 12 more authors.
Current Cancer Therapy Reviews | Year: 2014

Composite lymphomas (CLs) are characterized by the rare occurrence of two or more morphologically and/or immunophenotypically different lymphomas in the same anatomic tissue site. Many different combinations of lymphoma have been reported including multiple B-cell lymphomas, B-cell and T-cell non Hodgkin lymphomas, non Hodgkin lymphomas and Hodgkin lymphoma and complex B-cell, T-cell and Hodgkin lymphoma cases. The two lymphoma components usually are not clonally related but the use of thorough molecular techniques revealed that in some cases the two components are clonally related suggesting origin from a common progenitor cell. Pathogenesis of these lymphomas remains not well defined and the etiology differs according to the types of lymphomas involved. Composite B-cell lymphomas with two distinct low grade components are rare and usually are characterized by the existence of two different unrelated progenitors. CLs consisting of two types of non Hodgkin lymphomas of the same lineage, mostly B-cells, represent in most of the cases tumor progression and transformation from an indolent B-cell lymphoma to diffuse large B-cell lymphoma (DLBCL) and the low grade and high grade components in this type of CL are often clonally related while a clonal link has also been reported in cases of CLs containing Hodgkin lymphoma with various non Hodgkin lymphomas. CLs must be carefully diagnosed because the containing disease entities may not only have different natural course but also may differ in prognosis and treatment. © 2014 Bentham Science Publishers.


Levidou G.,National and Kapodistrian University of Athens | Tzenou T.,National and Kapodistrian University of Athens | Kyrtsonis M.-C.,National and Kapodistrian University of Athens | Nikolaou E.,National and Kapodistrian University of Athens | And 13 more authors.
Current Angiogenesis | Year: 2013

Neovascularisation is a vital process underlying the development and progression of malignant neoplasms. Limited information on the subject is available regarding Waldenstrom's macroglobulinemia/Lymphoplasmacytic lymphoma (WM/LPL), a rare and usually indolent B-cell lymphoma. We therefore studied by immunohistochemistry microvessel characteristics and IL-6, IL-8, CXCR2 and VEGF expression in the bone marrow of WM/LPL patients and investigated any possible correlation with disease characteristics and outcome. Sixty-three patients were studied (47 WM and 16 LPL) of whom 32, 25 and 6 were low, intermediate and high risk respectively, according to the IPSSWM staging system. Seventy-six percent of the patients required treatment while 24% were asymptomatic and were regularly followed- up. Microvascular characteristics, i.e microvessel density (MVD), total vascular area (TVA) and several other sizeand shape-related parameters, were evaluated in CD34-stained bone marrow slides using computerized image analysis. A Histo-score (H-score) was calculated for IL-6, IL-8, CXCR2 and VEGF expression. IL-6, IL-8, IL-8 receptor CXCR2 and VEGF expression was observed in 84%, 43%, 89% and 90% respectively. A positive correlation between IL-6 and CXCR2 H-scores was observed; IL-6 and VEGF H-scores correlated with hypoalbulinemia and increased serum β2-microglobulin respectively and both with bone marrow lymphoplasmacytic infiltration and MVD. The degree of angiogenesis, microvessel shape, VEGF expression and CXCR2 expression correlated with a shorter time to first treatment in multivariate analysis. In conclusion, in WM/LPL, increased expression of Th-2 cytokines, CXCR2 and VEGF is implicated in neovascularization. CXCR2 and VEGF expression along with the extent and the architecture of the microvessels are brought forward as contributors to biologic aggressiveness reflected by a need for earlier treatment. © 2013 Bentham Science Publishers.


Angelopoulou M.K.,National and Kapodistrian University of Athens | Kalpadakis C.,University of Crete | Pangalis G.A.,Athens Medical Center Psychicon Branch | Kyrtsonis M.-C.,National and Kapodistrian University of Athens | Vassilakopoulos T.P.,National and Kapodistrian University of Athens
Leukemia and Lymphoma | Year: 2014

Nodal marginal zone lymphoma (NMZL) is one of the three well-recognized entities within the broad category of marginal zone lymphoma, representing approximately 10% of the cases in this group. Patients typically present with nodal disease, usually at advanced stages, and a thorough work-up and staging are necessary in order to exclude occult extranodal involvement. NMZL shares many similarities with splenic marginal zone (SMZL) and mucosa-associated lymphoid tissue (MALT) lymphomas, such as cytology, immunophenotype, genetic abnormalities and maybe even a common cell of origin: a post-germinal memory B-cell. NMZL is characterized by an indolent course, but its prognosis is generally considered less favorable than that of SMZL and MALT lymphoma, with reported 5-year overall survival rates ranging between 55% and 89%. Therapeutic recommendations for NMZL are derived from small retrospective series or studies on larger cohorts of indolent lymphomas, which include a limited number of patients with NMZL. For localized disease, radiotherapy appears to be the treatment of choice, while rituximab-containing therapy is recommended for advanced stage disease. Due to the rarity of NMZL it is very difficult to perform prospective trials, and an international collaborative effort is necessary in order to better understand the biological features and provide evidence-based treatment recommendations. © 2014 Informa UK, Ltd.


Sachanas S.,Athens Medical Center Psychicon Branch | Angelopoulou M.K.,National and Kapodistrian University of Athens | Korkolopoulou P.,National and Kapodistrian University of Athens | Kalpadakis C.,University of Crete | And 7 more authors.
Current Angiogenesis | Year: 2013

Data concerning angiogenesis in chronic lymphocytic leukaemia (CLL) indicate that CLL patients are characterized by various abnormalities in the angiogenic profile including increased microvessel density in lymph nodes and in bone marrow and increased levels of certain pro-angiogenic vascular growth factors. Vascular endothelial growth factor (VEGF) and its receptors, basic fibrobast growth factor (bFGF) and matrix metalloproteinases(MMPs) were found to be highly expressed in CLL patients while there was no difference in angiogenin expression between CLL patients and healthy individuals. VEGF is implicated in CLL pathogenesis through various mechanisms. Enhanced angiogenesis in CLL has been associated in several reports with disease characteristics and patients' survival. Various anti-angiogenic agents targeting angiogenesis related pathways such as immunomodulatory drugs and receptor tyrosine kinase inhibitors have already been entered in clinical trials. Among them lenalidomide is the most promising antiangiogenic drug showing a significant efficacy in relapsed/refractory CLL patients. © 2013 Bentham Science Publishers.

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