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Mylona E.,Evagelismos Hospital | Melissaris S.,National and Kapodistrian University of Athens | Giannopoulou I.,National and Kapodistrian University of Athens | Theohari I.,National and Kapodistrian University of Athens | And 3 more authors.
European Journal of Surgical Oncology | Year: 2014

Aims To investigate the expression pattern of Y-box-binding protein 1 (YB1) in breast carcinomas, its clinicopathological and prognostic value, and its association with the breast cancer stem cell phenotype [CD44+/ CD24-/low]. Methods and results Immunohistochemistry was performed on 225 paraffin embedded specimens of invasive breast carcinomas to detect the expression of the proteins YB1, ER, PR, HER2, p53, Ki67, bcl-2, CD44 and CD24. YB1 protein was detected in the nuclei, the cytoplasm and the stroma of the tumor cells. Cytoplasmic YB1 was detected more often in carcinomas of ductal type (p = 0.002), of higher nuclear grade (p < 0.001), with lack of ER expression (p = 0.002), positive expression of p53 and Ki67 (p = 0.002 and p = 022, respectively), and with present CD44+/CD24-/low breast cancer stem cells (p = 0.001), while its association with bcl-2 was found to be inverse (p = 0.042). Nuclear YB1 was found to exert unfavorable impact on the disease-free survival of the unselected patients (p = 0.05) and the patients having been subjected to adjuvant chemotherapy and radiotherapy (p = 0.036 and p = 0.05, respectively). Conclusions Cytoplasmic YB1 is associated with an aggressive and "stem cell-like" tumor phenotype, while nuclear localization discriminates patients at high risk for recurrence, especially those who are subjected to chemo- and radiotherapy.© 2013 Published by Elsevier Ltd.


Mylona E.,Evagelismos Hospital | Vamvakaris I.,National and Kapodistrian University of Athens | Giannopoulou I.,National and Kapodistrian University of Athens | Theohari I.,National and Kapodistrian University of Athens | And 3 more authors.
Histopathology | Year: 2013

Aims: Our purpose was to investigate, in breast carcinomas, the prognostic importance of the proteins Wnt1 and glycogen synthasekinase (GSK)-3β, and their associations with classic clinicopathological indices. Methods and results: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 288 invasive breast carcinomas to detect the expression of the proteins Wnt1, GSK3β, oestrogen receptor (ER), progesterone receptor (PR), erbB2, p53, Ki67, caspase-3 and β-catenin. Both Wnt1 and GSK3β were detected predominantly in the cytoplasm of the invasive tumour cells and the in-situ component, while GSK3β was also detected in the stromal fibroblasts. Wnt1 immunoreactivity in the invasive tumour cells showed an inverse association with histological grade (P = 0.002), Ki67 (P = 0.008) and p53 (P = 0.031), while its relation with ER, erbB2 and caspase-3 was found to be positive (P = 0.007, P = 0.018 and P = 0.03, respectively). Cytoplasmic Wnt1 expression was related to a favourable prognosis within the subgroup of patients with stage II disease (P = 0.032). Conclusions: Wnt1 expression in the invasive tumour cells seems to promote differentiation and apoptosis, while being related inversely to proliferation. Therefore, this suggests its participation in the primary stages of breast carcinogenesis. The latter is supported further by the immunodetection of Wnt1 in in-situ carcinomas. © 2013 Blackwell Publishing Ltd.


Samarkos M.,Evagelismos Hospital | Mylona E.,Evagelismos Hospital | Kapsimali V.,National and Kapodistrian University of Athens
Seminars in Arthritis and Rheumatism | Year: 2012

Objectives: Despite the experimental research data on antiphospholipid syndrome (APS), the pathogenesis of thrombosis and fetal loss remains unknown. The objective of this study was to analyze the major advances in the field of complement activation as a possible thrombosis mechanism in the APS. Methods: The authors conducted a systemic analysis of the English literature and summarized both animal and human data that indicate the inappropriate complement activation as a mechanism causing thrombosis in the APS. Results: The important role of complement activation in the pathogenesis of fetal loss was established using mice deficient in a complement regulatory protein. Further studies have shown that the infusion of human IgG antiphospholipid antibodies (aPL) induced fetal loss in pregnant mice, an effect that was abrogated by the concurrent administration of a C3 convertase inhibitor. Further studies suggested that C5a and neutrophils were the key components responsible for fetal injury. Moreover, use of F(ab)'2 fragments of aPL suggested the complement activation occurred mainly via the classical pathway. Other studies using models of induced thrombosis suggested that antibodies against β2GPI required the presence of terminal complement components to induce thrombus formation, and mice deficient in C3 or C5 were found to be resistant to aPL-induced thrombosis. Based on the aforementioned findings, it has been suggested that heparin prevents fetal loss in patients with APS by inhibiting complement activation rather than by its anticoagulant effect. Conclusions: The studies on complement are significant because they shift the focus of research in APS from thrombosis to inflammation. However, as human data are limited, more clinical research is necessary before the above findings translate in changes in the management of APS. © 2012 Elsevier Inc.


Mylona E.,Evagelismos Hospital | Tzelepis K.,National and Kapodistrian University of Athens | Theohari I.,National and Kapodistrian University of Athens | Giannopoulou I.,National and Kapodistrian University of Athens | And 2 more authors.
Histopathology | Year: 2013

Aims: To study the clinicopathological and prognostic value of cyclin D1 overexpression in patients with breast carcinoma. Methods and results: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 290 invasive breast carcinomas to detect the proteins cyclin D1, oestrogen receptor (ER), progesterone receptor (PR), p53, c-erbB2, and topoisomerase IIα (topoIIα). Cyclin D1 staining was quantified using a computerized image analysis method. Cyclin D1 overexpression characterized smaller, ER-positive and PR-positive tumours (P=0.017, P<0.0001, and P<0.0001, respectively), of a lower histological and nuclear grade (P = 0.011 and P<0.0001, respectively), and with reduced expression of topoIIα (P=0.001) and p53 (P<0.001). Cyclin D1 was found to have an independent favourable impact on the overall survival of both the unselected cohort of patients (P=0.011) and of patients with ER-negative and lymph node-positive tumours (P=0.034 and P=0.015, respectively). In triple-negative tumours, cyclin D1 overexpression was found to have independent favourable impacts on both overall and relapse-free survival (P=0.002 for both). Conclusions: This is the first immunohistochemical study to dissociate the advantageous prognostic effect of cyclin D1 overexpression from its association with ER expression, and to provide evidence that cyclin D1 overexpression may be a marker of prolonged survival in patient subgroups with aggressive phenotypes. © 2012 Blackwell Publishing Ltd.


Mylona E.,Evagelismos Hospital | Melissaris S.,National and Kapodistrian University of Athens | Nomikos A.,National and Kapodistrian University of Athens | Theohari I.,National and Kapodistrian University of Athens | And 3 more authors.
Pathology Research and Practice | Year: 2014

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p = 0.019 and p = 0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p = 0.05), prolonging the RF survival of the patients (p = 0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases. © 2014 Elsevier GmbH.


Nerantzis C.E.,Forensic Medical Service of Athens | Koulouris S.N.,Evagelismos Hospital | Marianou S.K.,Forensic Medical Service of Athens | Pastromas S.C.,Evagelismos Hospital | And 2 more authors.
Journal of Forensic Sciences | Year: 2011

Sudden unexpected death is frequent in street heroin addicts. We conducted a histologic study of the sinus node (SN) to offer some evidence about the possible arrhythmogenic cause of death. Postmortem coronary angiography and microscopic examination of the SN and the perinodal area were performed in 50 heroin addicts (group 1) and in 50 nonaddicts (group 2), all men (16-40years old). In heroin addicts, fatty and/or fibrous tissue replaced SN tissue in 21 cases (42%). Perinodal infiltration was found in 15 cases (30%). Fibromuscular dysplasia in branches of the sinus node artery (SNA) was found in eight cases (16%). Inflammation with focal and/or diffuse concentration of round cells was detected in the SN in 22 cases (44%). Old mural thrombi were also found in 13 cases (26%). The histologic changes in the SN and perinodal area offer an explanation about the possible mechanism of arrhythmia and sudden death in this population. © 2011 American Academy of Forensic Sciences.


PubMed | National Technical University of Athens, Evagelismos Hospital and National and Kapodistrian University of Athens
Type: Journal Article | Journal: Hematology (Amsterdam, Netherlands) | Year: 2016

During bone marrow engraftment following BMT there is a re-establishment of fetal erythropoiesis, expressed by the increase of F-cells. This seems to depend on several factors such as underlying disease, conditioning before therapy and other mechanisms concerning both the donor and the recipient bone marrow. The aim of this work was to study the factors influencing F-cell production during bone marrow engraftment following transplantation. We studied 28 patients who underwent allogeneic bone marrow transplantation, for various hematological malignancies (CML, AML, ALL, CMML and SAA). F-cells were estimated on peripheral blood smears by indirect immunofluorescence. Overall, there was an F-cell increase after BMT in comparison with values before BMT; this increase was significant on days 15-50 (p <.01). F-cell on days 18, 25, 32 and 40 following transplantation were significantly higher (p <.01) in patients who have had increased F-cell numbers post-chemotherapy before BMT, compared with the patients who did not show any increase of the F-cell number post chemotherapy. During the first month following transplantation (day 7 to day 40) patients who were transplanted from high F-cell donors failed to show any significant differences in their F-cell numbers in comparison to those transplanted from low F-cell donors. However, the F-cell increase became significantly higher in the former group between days 50 and 120. This observation implies that the stressed erythropoiesis of the initial phase does not allow revealing the varying F-cell production of the capacities donor bone marrow, while later, when the graft has settled, the high F-cell donors reveal this property of the host.


Samarkos M.,Evagelismos Hospital | Giannopoulou C.,Evagelismos Hospital | Karantoni E.,Evagelismos Hospital | Papastamopoulos V.,Evagelismos Hospital | And 2 more authors.
Sexually Transmitted Infections | Year: 2011

We report the case of a HIV and syphilis co-infected patient who presented with headache and rash and was found to have syphilitic periostitis. Our case illustrates a rare manifestation of early syphilis and presents the diagnostic dilemmas that can arise in HIV and syphilis co-infected patients.


Naoum C.,Evagelismos Hospital
Kosmetische Medizin | Year: 2010

Implanting hyaluronic acid for cosmetic reasons in woman's forehead provoked painful, erythematous, infiltrated nodules "red angry bumps". In this paper, we examined this severe case and we discussed all the clinical, laboratory and therapeutical parameters.


Rizzo M.,University of Palermo | Berneis K.,University of Zürich | Koulouris S.,Evagelismos Hospital | Pastromas S.,Evagelismos Hospital | And 3 more authors.
International Journal of Clinical Practice | Year: 2010

Beyond low-density lipoprotein (LDL)-cholesterol concentrations, in recent years, several clinical studies have shown that both oxidised and small, dense LDL have a strong predictive role for the presence of vascular atherosclerosis. These two lipid parameters seem to have a synergistic impact on cardiovascular risk, with a greater importance in patients at higher-risk, such as those with type-2 diabetes. Increased levels of oxidised and small, dense LDL levels are a feature of diabetic dyslipidaemia, and small, dense LDL have been shown to be a good predictor of future cardiovascular events, at both univariate and multivariate analyses. On the other hand, although the association of oxidised LDL with surrogate markers of atherosclerosis is consistent, the correlation with hard clinical end points seems to be smaller. Yet, measurement of these two lipid parameters has not been widely used in daily practice because of the limited availability of clinical data and methodological problems: lack of availability of easy, cheap and reproducible essays for measurement of oxidised and, particularly, small, dense LDL has reduced their assessment in large clinical end-points trials. However, on the basis of available data, the therapeutic modulation of small, dense LDL is significantly associated with reduced cardiovascular risk, even after adjustment for confounding factors. In conclusion, the routine measurement of oxidised and small, dense LDL in patients with type-2 diabetes cannot be recommended in daily clinical practice so far; yet, their measurement is strongly encouraged to better understand their role on the cardiovascular risk of patients with type-2 diabetes. © 2010 Blackwell Publishing Ltd.

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