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West Jerusalem, Israel

Gemer O.,Barzilai Medical Center | Lavie O.,Carmel Medical Center | Gdalevich M.,Barzilai Medical Center | Eitan R.,Rabin Medical Center | And 14 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2016

Objective: To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. Methods: This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. Results: We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10mm received RT, and 87% of patients with tumors depth of invasion >10mm and lymph-vascular space invasion received RT. Conclusions: This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation. © 2013 Wolters Kluwer Health, Inc. All rights reserved.

Saar-Ashkenazy R.,Ben - Gurion University of the Negev | Saar-Ashkenazy R.,Achva Academic College | Cohen J.E.,Sharett Institute of Oncology | Guez J.,Achva Academic College | And 5 more authors.
Journal of Traumatic Stress | Year: 2014

Memory deficits are a common complaint of patients with posttraumatic stress disorder (PTSD). Despite vivid trauma-related memory, previous studies report memory impairment for nontrauma-related stimuli when compared to controls, specifically in associative memory (Guez et al., 2011). Healthy individuals show hemispheric memory asymmetry with left-prefrontal lateralization of encoding and right-prefrontal lateralization of episodic retrieval, suggesting a role for interhemispheric communication in memory-related tasks (Gazzaniga, ; Ringo, Doty, Demeter, & Simard, ). Because brain magnetic resonance imaging (bMRI) studies in PTSD patients report volume changes in various regions, including white matter and corpus callosum (CC), we aimed to test the relationship between memory deficits and CC volume in PTSD patients. We probed for specific alterations in associative memory in PTSD and measured the volume of subportions within the CC employing bMRI. Our main finding was a reduction in CC white-matter volume in PTSD patients, as compared to controls, t(35) = -2.7, p = .010, that was correlated with lower associative performance (r = .76, p = .003). We propose that CC volume reduction is a substrate for the associative memory deficits found in PTSD. Copyright © 2014 International Society for Traumatic Stress Studies.

Saar-Ashkenazy R.,Ben - Gurion University of the Negev | Saar-Ashkenazy R.,Ashkelon Academic College | Saar-Ashkenazy R.,Achva Academic College | Shalev H.,Soroka University Medical Center | And 5 more authors.
Psychiatry Research - Neuroimaging | Year: 2015

Patients with posttraumatic stress disorder (PTSD) display abnormal emotional processing and bias towards emotional content. Most neurophysiological studies in PTSD found higher amplitudes of event-related potentials (ERPs) in response to trauma-related visual content. Here we aimed to characterize brain electrical activity in PTSD subjects in response to non-trauma-related emotion-laden pictures (positive, neutral and negative). A combined behavioral-ERP study was conducted in 14 severe PTSD patients and 14 controls. Response time in PTSD patients was slower compared with that in controls, irrespective to emotional valence. In both PTSD and controls, response time to negative pictures was slower compared with that to neutral or positive pictures. Upon ranking, both control and PTSD subjects similarly discriminated between pictures with different emotional valences. ERP analysis revealed three distinctive components (at ~300, ~600 and ~1000. ms post-stimulus onset) for emotional valence in control subjects. In contrast, PTSD patients displayed a similar brain response across all emotional categories, resembling the response of controls to negative stimuli. We interpret these findings as a brain-circuit response tendency towards negative overgeneralization in PTSD. © 2015 Elsevier Ireland Ltd.

Uzana R.,Sharett Institute of Oncology | Eisenberg G.,Sharett Institute of Oncology | Merims S.,Sharett Institute of Oncology | Frankenburg S.,Sharett Institute of Oncology | And 6 more authors.
PLoS ONE | Year: 2015

Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC). Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs) and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+T-APCs). We demonstrate that, following trogocytosis, CD8+T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1) Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2) Fratricide (killing) of CD8+T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response. © 2015 Uzana et al.

Sivan S.,Ella Institute for Treatment and Research of Melanoma and Skin Cancer | Suzan F.,Sharett Institute of Oncology | Rona O.,Ella Institute for Treatment and Research of Melanoma and Skin Cancer | Tamar H.,Sharett Institute of Oncology | And 7 more authors.
Clinical and Developmental Immunology | Year: 2012

The search for melanoma biomarkers is crucial, as the incidence of melanoma continues to rise. We have previously demonstrated that serum CEACAM1 (sCEACAM1) is secreted from melanoma cells and correlates with disease progression in metastatic melanoma patients. Here, we have used a different cohort of melanoma patients with regional or metastatic disease (N = 49), treated with autologous vaccination. By monitoring sCEACAM1 in serum samples obtained prior to and after vaccination, we show that sCEACAM1 correlates with disease state, overall survival, and S100B. The trend of change in sCEACAM1 following vaccination (increase/decrease) inversely correlates with overall survival. DTH skin test is used to evaluate patients' anti-melanoma immune response and to predict response to vaccination. Importantly, sCEACAM1 had a stronger prognostic value than that of DTH, and when sCEACAM1 decreased following treatment, this was the dominant predictor of increased survival. Collectively, our results point out the relevance of sCEACAM1 in monitoring melanoma patients. Copyright © 2012 Sapoznik Sivan et al.

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