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Carvajal-Hausdorf D.E.,Yale University | Schalper K.A.,Yale University | Pusztai L.,Yale University | Psyrri A.,National and Kapodistrian University of Athens | And 5 more authors.
Journal of the National Cancer Institute | Year: 2015

Background: Studies have shown that antibodies targeting the intracellular (ICD) or extracellular domains (ECD) of human epidermal growth factor receptor 2 (HER2) are equivalent when traditional methods are used. We describe a new method to quantify ICD and ECD expression separately and assess the prognostic value of domain-specific HER2 results in patients who received adjuvant trastuzumab therapy. Methods: We measured HER2 protein expression with quantitative immunofluorescence (QIF) in tissue microarrays (TMA) using two different antibodies targeting the ICD (CB11 and A0485) and ECD (SP3 and D8F12). We assessed the prognostic value of ICD and ECD expression in 180 patients from a clinical trial of adjuvant chemotherapy followed by trastuzumab (HeCOG 10/05). We performed an exploratory univariate domain-specific, disease-free survival (DFS) analysis and compared DFS functions with Kaplan-Meier estimates. All statistical tests were two-sided. Results: HER2 ICD expression by QIF showed slightly higher sensitivity to predict ERBB2 (HER2) gene amplification than ECD expression, which was more specific and had higher positive predictive value. In the HeCOG 10/05 trial specimens, 15% of cases showed discordant results for ICD and ECD expression. High ECD was statistically associated with longer DFS (log-rank P =. 049, HR = 0.31, 95% CI = 0.144 to 0.997), while ICD status was not. Among patients with low ECD, there was no difference in DFS by ICD status. However, when ICD was high, high ECD was statistically associated with longer DFS (log-rank P =. 027, HR = 0.23, 95% CI = 0.037 to 0.82) compared with low ECD. Conclusion: Quantitative measurements of HER2 ICD and ECD expression in breast cancer suggest a subclassification of HER2-positive tumors. Trastuzumab-treated patients with high ECD showed better DFS than patients with low ECD. This suggests differential benefit from trastuzumab therapy based on HER2 ECD expression. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved. Source


Trakatelli M.,Papageorgiou Hospital | Morton C.,Stirling Community Hospital | Nagore E.,Instituto Valenciano Of Oncologia | Ulrich C.,Charite - Medical University of Berlin | And 3 more authors.
European Journal of Dermatology | Year: 2014

Background European guidelines for the management of basal cell carcinoma (BCC) prepared by the former BCC subcommittee of the Guidelines Committee of the European Dermatology Forum (EDF) were published in 2006. Objectives To present updated guidelines that include consensual expert definitions on various BCC types, prognosis and risk factors for BCC as well as review recommendations for diagnosis and treatment reflecting current published evidence. Methods These guidelines (S1 type) were prepared by the new BCC subgroup of the European Dermatology Forum (EDF)'s Guidelines Committee through extensive literature review (up to 2012) and expert experience; they were extensively discussed within the EDF subcommittee and approved by peer reviewers of the EDF. Results BCC is a common tumour with an incidence risingworldwide. Three major clinical types ofBCCare recognized: nodular, superficial and morpheaform. Four histological subtypes are defined: superficial, nodular, infiltrative and morpheaform. On the basis of the risk of relapse, three prognosis groups have been identified: high, intermediate and low risk. According to these classifications and evidence-based evaluation of the therapeutic strategies available, a decision tree is proposed for the management of BCCs. Conclusions. The guidelines offer a useful tool that will help dermatologists to select the most appropriate treatment for individual patients. Source


Georgiou E.,Papageorgiou Hospital | Kouidou S.,Aristotle University of Thessaloniki
Current Medicinal Chemistry | Year: 2011

Epigenetic modifications, which are heritable changes in gene expression not involving DNA sequence alterations, are important early events in the multi -step process of tumorigenesis. Among them, DNA methylation and histone acetylation are the most extensively studied. Although they are, by definition, somatically heritable, epigenetic modifications of DNA and histones are also reversible. This characteristic difference from genetic alterations makes them interesting targets for therapeutic intervention. The huge amount of knowledge gathered in the field of epigenetics the last decade, was followed by the development of novel therapies: old drugs finding new identity and new targets and an increasing list of novel compounds for the treatment of malignant diseases. Hematological malignancies offer a broad spectrum of diseases where epigenetic therapies are shown to be active, providing encouraging results. Some of the more recent reports on this field of therapeutic interventions are reviewed below. © 2011 Bentham Science Publishers Ltd. Source


Tselis N.,Klinikum Offenbach | Ratka M.,Klinikum Offenbach | Vogt H.-G.,Klinikum Offenbach | Kolotas C.,Institute for Radiotherapy | And 5 more authors.
Radiotherapy and Oncology | Year: 2011

Background: Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC. Patients and methods: From 2000 to 2007, 74 patients were treated for inoperable recurrent cervical lymphadenopathy. All patients had previously been treated with radical radiotherapy or chemoradiation with or without surgery. The HDR-BRT delivered a median salvage dose of 30.0 Gy (range, 12.0-36.0 Gy) in twice-daily fractions of 2.0-5.0 Gy in 71 patients and of 30.0 Gy (range, 10.0-36.0 Gy) in once-daily fractions of 6.0-10.0 Gy in three patients. Results: The overall and disease-free survival rates at one, two and three years were 42%, 19%, 6%, and 42%, 37% and 19%, respectively. The local control probability at one, two and three years was 67% at all three time points. Grade III-IV complications occurred in 13% of patients. Conclusions: In patients with inoperable recurrent neck disease from HNC, hypofractionated accelerated CT-guided IRT-HDR-BRT can play an important role in providing palliation and tumor control. © 2010 Elsevier Ireland Ltd. All rights reserved. Source


Pateinakis P.,Papageorgiou Hospital | Pyrpasopoulou A.,Hippokration General Hospital
BioMed Research International | Year: 2014

Autoimmunity remains a complex physiologic deviation, enabled and perpetuated by a variety of interplayers and pathways. Simplistic approaches, targeting either isolated end-effectors of more centrally placed interactors of these mechanisms, are continuously tried in an effort to comprehend and halt cascades with potential disabling and deleterious effects in the affected individuals. This review focuses on theoretical and clinically proved effects of rituximab-induced CD20+ B cell depletion on different systemic autoimmune diseases and extrapolates on pathogenetic mechanisms that may account for different interindividual or interdisease responses. © 2014 Panagiotis Pateinakis and Athina Pyrpasopoulou. Source

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