96 results on '"Vlodavsky E"'
Search Results
2. Evaluation of muscle capillary basement membrane in inflammatory myopathy: A morphometric ultrastructural study
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Vlodavsky, E. A., Ludatscher, Ruth M., Sabo, Edmond, and Kerner, Hedviga
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- 1999
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3. The effect of oxygenation level on cerebral post-traumatic apoptotsis is modulated by the 18-kDa translocator protein (also known as peripheral-type benzodiazepine receptor) in a rat model of cortical contusion
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Soustiel, J. F., Palzur, E., Vlodavsky, E., Veenman, L., and Gavish, M.
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- 2008
4. Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix metalloproteinase-9 in the rat model of traumatic brain injury
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Vlodavsky, E., Palzur, E., and Soustiel, J. F.
- Published
- 2006
5. Meningioma with extensive necrotizing granulomatous changes: possible mimic of inflammatory dural lesions
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Vlodavsky, E, Konstantinesku, M, Pery-Eran, A, and Zaaroor, M
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- 2004
6. Splenic littoral cell haemangioendothelioma: a new low-grade variant of malignant littoral cell tumour
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Ben-Izhak, O, Bejar, J, Ben-Eliezer, S, and Vlodavsky, E
- Published
- 2001
7. Pediatric Tumors
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Elhasid, R., Vlodavsky, E., Nachtigal, A., Keidar, Z., Postovsky, S., and Ben Arush, M. Weyl
- Published
- 2001
8. Amyloid colitis mimicking collagenous colitis
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GROISMAN, G. M., LACHTER, J., and VLODAVSKY, E.
- Published
- 1997
9. Recurrent Upper Gastrointestinal Bleeding Caused by a Giant Brunneroma--Report of a Case Treated Endoscopically
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Yassin, K., primary, Vlodavsky, E., additional, and Eliakim, R., additional
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- 2002
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10. Gliosarcoma with liposarcomatous differentiation: the new member of the lipid-containing brain tumors family.
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Vlodavsky E, Konstantinesku M, and Soustiel JF
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- 2006
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11. Prolonged retention of laminaria fragments: a rare complication of induced abortion.
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Lachman E, Czernobilsky B, Ben-David M, Vlodavsky E, Lifschitz-Mercer B, and Mammet Y
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- 2004
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12. Accelerated pulmonary nodulosis and sterile pleural effusion in a patient with psoriatic arthropathy during methotrexate therapy: a case report.
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Balbir-Gurman A, Guralnik L, Best L, Vlodavsky E, Yigla M, Menahem Nahir A, and Braun-Moscovici Y
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- 2009
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13. A novel loss-of-function mutation in LACC1 underlies hereditary juvenile arthritis with extended intra-familial phenotypic heterogeneity.
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Butbul Aviel Y, Ofir A, Ben-Izhak O, Vlodavsky E, Karbian N, Brik R, Mevorach D, and Magen D
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- Adolescent, Adult, Arthritis, Juvenile pathology, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Cytokines blood, Female, Flow Cytometry, Gene Editing, Humans, Immunoblotting, Male, Pedigree, Exome Sequencing, Young Adult, Arthritis, Juvenile genetics, Intracellular Signaling Peptides and Proteins genetics, Loss of Function Mutation genetics
- Abstract
Objective: To investigate phenotypic and molecular characteristics of a consanguineous family with autosomal-recessive, polyarticular, juvenile isiopathic arthriris (JIA) with extra-articular manifestations, including renal amyloidosis and Crohn's disease, associated with a novel homozygous truncating variant in LACC1., Methods: Whole exome sequencing (WES) or targeted Sanger verification were performed in 15 participants. LACC1 expression and cytokine array were analysed in patient-derived and CRISPR/Cas9-generated LACC1-knockout macrophages (Mϕ)., Results: A homozygous truncating variant (p.Glu348Ter) in LACC1 was identified in three affected and one asymptomatic family member, and predicted harmful by causing premature stop of the LACC1 protein sequences, and by absence from ethnically-matched controls and public variation databases. Expression studies in patient-derived macrophages (Mϕ) showed no endogenous p.Glu348Ter-LACC1 RNA transcription or protein expression, compatible with nonsense-mediated mRNA decay. WES analysis in the asymptomatic homozygous subject for p. Glu348Ter-LACC1 detected an exclusive heterozygous variant (p.Arg928Gln) in complement component C5. Further complement activity analysis suggested a protective role for the p.Arg928Gln-C5 variant as a phenotypic modifier of LACC1-associated disease. Finally, cytokine profile analysis indicated increased levels of pro-inflammatory cytokines in LACC1-disrupted as compared with wild-type Mϕ., Conclusions: Our findings reinforce the role of LACC1 disruption in autosomal-recessive JIA, extend the clinical spectrum and intra-familial heterogeneity of the disease-associated phenotype, indicate a modulatory effect of complement factor C5 on phenotypic severity, and suggest an inhibitory role for wild-type LACC1 on pro-inflammatory pathways., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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14. Heparanase promotes glioma progression via enhancing CD24 expression.
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Barash U, Spyrou A, Liu P, Vlodavsky E, Zhu C, Luo J, Su D, Ilan N, Forsberg-Nilsson K, Vlodavsky I, and Yang X
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- Animals, Brain Neoplasms metabolism, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, Female, Glioma metabolism, Heterografts, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Neural Cell Adhesion Molecule L1 metabolism, Signal Transduction, Brain Neoplasms pathology, CD24 Antigen metabolism, Glioma pathology, Glucuronidase metabolism
- Abstract
Heparanase is an endo-β-d-glucuronidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans. Compelling evidence tie heparanase levels with all steps of tumor formation including tumor initiation, growth, metastasis and chemo-resistance, likely involving augmentation of signaling pathways and gene transcription. In order to reveal the molecular mechanism(s) underlying the protumorigenic properties of heparanase, we established an inducible (Tet-on) system in U87 human glioma cells and applied gene array methodology in order to identify genes associated with heparanase induction. We found that CD24, a mucin-like cell adhesion protein, is consistently upregulated by heparanase and by heparanase splice variant devoid of enzymatic activity, whereas heparanase gene silencing was associated with decreased CD24 expression. This finding was further substantiated by a similar pattern of heparanase and CD24 immunostaining in glioma patients (Pearson's correlation; R = 0.66, p = 0.00001). Noteworthy, overexpression of CD24 stimulated glioma cell migration, invasion, colony formation in soft agar and tumor growth in mice suggesting that CD24 functions promote tumor growth. Likewise, anti-CD24 neutralizing monoclonal antibody attenuated glioma tumor growth, and a similar inhibition was observed in mice treated with a neutralizing mAb directed against L1 cell adhesion molecule (L1CAM), a ligand for CD24. Importantly, significant shorter patient survival was found in heparanase-high/CD24-high tumors vs. heparanase-high/CD24-low tumors for both high-grade and low-grade glioma (p = 0.02). Our results thus uncover a novel heparanase-CD24-L1CAM axis that plays a significant role in glioma tumorigenesis., (© 2019 UICC.)
- Published
- 2019
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15. Cerebral Liposarcoma Embolus From Heart Metastasis Successfully Treated by Endovascular Extraction Followed by Cardiac Surgery.
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Passhak M, Amsalem Y, Vlodavsky E, Varaganov I, and Bar-Sela G
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- Adult, Biopsy, Cerebral Angiography methods, Computed Tomography Angiography, Echocardiography, Transesophageal, Heart Neoplasms complications, Heart Neoplasms diagnostic imaging, Heart Neoplasms secondary, Humans, Infarction, Middle Cerebral Artery diagnostic imaging, Infarction, Middle Cerebral Artery etiology, Intracranial Embolism diagnostic imaging, Intracranial Embolism etiology, Liposarcoma complications, Liposarcoma diagnostic imaging, Liposarcoma secondary, Male, Perfusion Imaging methods, Treatment Outcome, Cardiac Surgical Procedures, Embolectomy methods, Endovascular Procedures, Heart Neoplasms surgery, Infarction, Middle Cerebral Artery surgery, Intracranial Embolism surgery, Liposarcoma surgery, Metastasectomy methods, Neoplastic Cells, Circulating pathology
- Abstract
The current case presents a patient with a tumor emboli stroke as a presenting symptom of a liposarcoma metastasis to the heart that was treated successfully with endovascular mechanical retrieval, followed by subsequent cardiac surgery. The patient is still alive, under chemotherapy treatment, 3 years following the interventions. This scenario should be considered as a part of the differential diagnosis of oncology patients presenting with new central neurological symptoms. This active approach can be an effective treatment if the patient is fit and there is no evidence of widespread disease.
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- 2018
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16. Fortuitous administration of denosumab in breast carcinoma with osteoclastic giant cells.
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Turgeman I, Flechter E, Vlodavsky E, Militianu D, Keidar Z, Haddad E, and Bar-Sela G
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Density Conservation Agents administration & dosage, Bone Neoplasms diagnostic imaging, Bone Neoplasms secondary, Bone Neoplasms surgery, Breast Neoplasms drug therapy, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Osteoclasts drug effects, Bone Neoplasms pathology, Breast Neoplasms pathology, Denosumab administration & dosage, Osteoclasts pathology
- Abstract
Breast carcinoma with osteoclastic giant cells (OGCs) is a rare entity characterized by an admixture of giant cells and malignant epithelial cells within an inflammatory and vascular stroma. Denosumab is a monoclonal antibody that targets the pathway for osteoclast formation and activation, indicated for the prevention of skeletal-related events in patients with bone metastases, as well as for the treatment of giant cell tumor of bone. We report a patient who presented with aggressive bone recurrence of breast cancer 12 years after her original diagnosis, showing a transformed histology that included multinucleated OGCs, and that was refractory to traditional therapy. Misdiagnosed with a tumor-to-tumor metastasis of breast cancer to a giant cell tumor of bone, she was treated with denosumab for her presumed primary bone disease and had a remarkable clinical and radiological response. To the best of our knowledge, this is the first report of breast cancer with OGCs occurring initially in a metastasis while absent in the original tumor and the first description of its successful treatment with denosumab. This case sheds light on the development of giant cells in the tumor microenvironment and suggests the potential use of denosumab in the management of cancers with giant cell elements.
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- 2018
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17. Investigating the cardiac pathology of SCO2-mediated hypertrophic cardiomyopathy using patients induced pluripotent stem cell-derived cardiomyocytes.
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Hallas T, Eisen B, Shemer Y, Ben Jehuda R, Mekies LN, Naor S, Schick R, Eliyahu S, Reiter I, Vlodavsky E, Katz YS, Õunap K, Lorber A, Rodenburg R, Mandel H, Gherghiceanu M, and Binah O
- Subjects
- Action Potentials drug effects, Adult, Arrhythmias, Cardiac pathology, Caffeine pharmacology, Cardiomyopathy, Hypertrophic physiopathology, Carrier Proteins genetics, Cell Differentiation, Female, Heart Rate drug effects, Humans, Induced Pluripotent Stem Cells ultrastructure, Isoproterenol pharmacology, Male, Mitochondria metabolism, Mitochondria ultrastructure, Mitochondrial Proteins genetics, Models, Biological, Molecular Chaperones, Mutation genetics, Myocardial Contraction drug effects, Myocytes, Cardiac ultrastructure, Cardiomyopathy, Hypertrophic pathology, Carrier Proteins metabolism, Induced Pluripotent Stem Cells metabolism, Mitochondrial Proteins metabolism, Myocytes, Cardiac metabolism
- Abstract
Mutations in SCO2 are among the most common causes of COX deficiency, resulting in reduced mitochondrial oxidative ATP production capacity, often leading to hypertrophic cardiomyopathy (HCM). To date, none of the recent pertaining reports provide deep understanding of the SCO2 disease pathophysiology. To investigate the cardiac pathology of the disease, we were the first to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) from SCO2-mutated patients. For iPSC generation, we reprogrammed skin fibroblasts from two SCO2 patients and healthy controls. The first patient was a compound heterozygote to the common E140K mutation, and the second was homozygote for the less common G193S mutation. iPSC were differentiated into cardiomyocytes through embryoid body (EB) formation. To test the hypothesis that the SCO2 mutation is associated with mitochondrial abnormalities, and intracellular Ca
2+ -overload resulting in functional derangements and arrhythmias, we investigated in SCO2-mutated iPSC-CMs (compared to control cardiomyocytes): (i) the ultrastructural changes; (ii) the inotropic responsiveness to β-adrenergic stimulation, increased [Ca2+ ]o and angiotensin-II (AT-II); and (iii) the Beat Rate Variability (BRV) characteristics. In support of the hypothesis, we found in the mutated iPSC-CMs major ultrastructural abnormalities and markedly attenuated response to the inotropic interventions and caffeine, as well as delayed afterdepolarizations (DADs) and increased BRV, suggesting impaired SR Ca2+ handling due to attenuated SERCA activity caused by ATP shortage. Our novel results show that iPSC-CMs are useful for investigating the pathophysiological mechanisms underlying the SCO2 mutation syndrome., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)- Published
- 2018
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18. Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome.
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Falik-Zaccai TC, Barsheshet Y, Mandel H, Segev M, Lorber A, Gelberg S, Kalfon L, Ben Haroush S, Shalata A, Gelernter-Yaniv L, Chaim S, Raviv Shay D, Khayat M, Werbner M, Levi I, Shoval Y, Tal G, Shalev S, Reuveni E, Avitan-Hersh E, Vlodavsky E, Appl-Sarid L, Goldsher D, Bergman R, Segal Z, Bitterman-Deutsch O, and Avni O
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- 2017
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19. Post-traumatic cytotoxic edema is directly related to mitochondrial function.
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Vlodavsky E, Palzur E, Shehadeh M, and Soustiel JF
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- Animals, Brain Edema drug therapy, Cyclosporine administration & dosage, Cyclosporine pharmacology, Intracranial Pressure, Mitochondrial Membranes metabolism, Mitochondrial Membranes pathology, Oligomycins administration & dosage, Oligomycins pharmacology, Rats, Rats, Sprague-Dawley, Brain Edema etiology, Brain Injuries, Traumatic complications, Mitochondria pathology
- Abstract
Cerebral edema represents a major threat following traumatic brain injury. However, therapeutic measures for control of intracranial pressure alone have failed to restore cerebral metabolism and improve neurological outcome. Since mitochondrial damage results in ATP depletion and deactivation of membrane ionic pumps, we hypothesized that modulation of ATP bioavailability may directly affect cytotoxic edema. Intracranial pressure measurements were performed in Sprague-Dawley rats treated by intraperitoneal injection of dimethylsulfoxide (vehicle), cyclosporine A (CsA), or Oligomycin B (OligB) following cortical contusion and further correlated with water content, mitochondrial damage, and electron microscopic assessment of neuronal and axonal edema. As hypothesized, ultra-structural figures of edema closely correlated with intracranial pressure elevation, increased water content and mitochondrial membrane permeabilization expressed by loss of transmembrane mitochondrial potential. Further, mitochondrial damage evidenced ultra-structurally by figures of swollen mitochondria with severely distorted cristae correlated with both cytotoxic edema and mitochondrial dysfunction. Importantly, cerebral edema and mitochondrial impairment were significantly worsened by treatment with OligB, whereas a noticeable improvement could be observed in animals that received injections of CsA. Since OligB and CsA are responsible for symmetrical and opposite effects on oxidative metabolism, these findings support the hypothesis of a causative relationship between edema and mitochondrial function., (© The Author(s) 2015.)
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- 2017
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20. Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria.
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Mandel H, Saita S, Edvardson S, Jalas C, Shaag A, Goldsher D, Vlodavsky E, Langer T, and Elpeleg O
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- Animals, DNA Mutational Analysis, Exome, Fatal Outcome, Female, High-Temperature Requirement A Serine Peptidase 2, Humans, Infant, Infant, Newborn, Male, Metabolism, Inborn Errors genetics, Metabolism, Inborn Errors pathology, Metabolism, Inborn Errors physiopathology, Mice, Neurodegenerative Diseases genetics, Neurodegenerative Diseases pathology, Neurodegenerative Diseases physiopathology, Pedigree, Syndrome, Apoptosis, Metabolism, Inborn Errors metabolism, Mitochondria metabolism, Mitochondrial Proteins genetics, Mutation, Neurodegenerative Diseases metabolism, Serine Endopeptidases genetics
- Abstract
Background: Cell survival critically depends on the integrity of mitochondria, which play a pivotal role during apoptosis. Extensive mitochondrial damage promotes release of pro-apoptotic factors from the intermembrane space of mitochondria. Released mitochondrial proteins include Smac/DIABLO and HTRA2/Omi, which inhibit the cytosolic E3 ubiquitin ligase XIAP and other inhibitors of apoptosis proteins., Aims: Here we investigated the cause of extreme hypertonia at birth, alternating with hypotonia, with the subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, intractable seizures and early death in four patients from two unrelated families. The patients showed lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, evolving brain atrophy and disturbed cristae structure in muscle mitochondria., Methods and Results: Using whole-exome sequencing, we identified missplicing mutation and a 5 bp deletion in HTRA2, encoding HTRA2/Omi. This protein was completely absent from the patients' fibroblasts, whose growth was impaired and which were hypersensitive to apoptosis. Expression of HtrA2/Omi or of the proteolytically inactive HTRA2/Omi protein restored the cells' apoptotic resistance. However, cell growth was only restored by the proteolytically active protein., Conclusions: This is the first report of recessive deleterious mutations in HTRA2 in human. The clinical phenotype, the increased apoptotic susceptibility and the impaired cell growth recapitulate those observed in the Htra2 knockout mice and in mutant mice with proteolytically inactive HTRA2/Omi. Together, they underscore the importance of both chaperone and proteolytic activities of HTRA2/Omi for balanced apoptosis sensitivity and for brain development. Absence of HTRA2/Omi is associated with severe neurodegenerative disorder of infancy, abnormal mitochondria, 3-methylglutaconic aciduria and increased sensitivity to apoptosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
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21. An 8-Year-Old Child with Malignant Deciduoid Mesothelioma of the Abdomen: Report of a Case and Review of the Literature.
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Wolff-Bar M, Dujovny T, Vlodavsky E, Postovsky S, Morgenstern S, Braslavsky D, Nissan A, Steinberg R, and Feinmesser M
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- Abdominal Pain etiology, Biopsy, Child, Female, Humans, Mesothelioma complications, Mesothelioma therapy, Peritoneal Neoplasms complications, Peritoneal Neoplasms therapy, Treatment Outcome, Mesothelioma pathology, Peritoneal Neoplasms pathology
- Abstract
Malignant mesothelioma is an uncommon tumor that usually arises in the pleural cavity of adults with a history of asbestos exposure. Less frequently, it appears in the peritoneum or other mesothelial surfaces. Deciduoid mesothelioma is a rare subtype that has been found at both sites. Of the 3 reported cases in children, 2 originated in the mesenterium and 1 in the pleura. We describe a 4th case of pediatric, malignant, deciduoid mesothelioma and a third case in the mesenteric cavity. The patient was an 8-year-old girl who presented with abdominal pain and fullness. Workup revealed extensive involvement of the abdomen by a serosa-based tumor. The clinical and pathologic findings are described, and the pertinent literature is reviewed.
- Published
- 2015
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22. Metastatic rhabdoid meningioma with BRAF V600E mutation and good response to personalized therapy: case report and review of the literature.
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Mordechai O, Postovsky S, Vlodavsky E, Eran A, Constantini S, Dotan E, Cagnano E, and Weyl-Ben-Arush M
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- Adenomatous Polyposis Coli Protein genetics, Child, Cyclin-Dependent Kinase Inhibitor p15 genetics, Cyclin-Dependent Kinase Inhibitor p16 genetics, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Imidazoles therapeutic use, Magnetic Resonance Imaging, Meningeal Neoplasms drug therapy, Meningioma drug therapy, Oximes therapeutic use, Precision Medicine, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Pyridones therapeutic use, Pyrimidinones therapeutic use, Rhabdoid Tumor drug therapy, Antineoplastic Agents therapeutic use, Meningeal Neoplasms genetics, Meningioma genetics, Mutation genetics, Proto-Oncogene Proteins B-raf genetics, Rhabdoid Tumor genetics
- Abstract
Rhabdoid meningioma is an aggressive phenotype of meningioma, associated with a poor prognosis. We present a very rare case of high-grade meningioma with rhabdoid features that eventually expressed in a coma state. Comprehensive genomic profiling using a Next Generation Sequencing (NGS) assay revealed three genomic alterations: activating BRAF mutation (V600E), loss of CDKN2A/2B, and APC I1307K. After treatment with BRAF inhibitor (dabrafenib), the child's clinical condition improved progressively. After seven months, an MEK inhibitor was added (trametinib).
- Published
- 2015
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23. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with a loss-of-function mutation in CDK5.
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Magen D, Ofir A, Berger L, Goldsher D, Eran A, Katib N, Nijem Y, Vlodavsky E, Tzur S, Behar DM, Fellig Y, and Mandel H
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- Base Sequence, Cells, Cultured, Cerebellum enzymology, Consanguinity, DNA Mutational Analysis, Developmental Disabilities enzymology, Developmental Disabilities genetics, Female, Genes, Recessive, Genetic Association Studies, Genetic Complementation Test, Homozygote, Humans, Infant, Infant, Newborn, Lissencephaly enzymology, Male, Mutation, Missense, Nervous System Malformations enzymology, Pedigree, Cerebellum abnormalities, Cyclin-Dependent Kinase 5 genetics, Lissencephaly genetics, Nervous System Malformations genetics
- Abstract
Lissencephaly comprises a heterogeneous group of developmental brain disorders of varying severity, involving abnormal cortical gyration. We studied a highly consanguineous Israeli Moslem family with a lethal form of autosomal recessive lissencephaly with cerebellar hypoplasia (LCH). Using microarray-based homozygosity mapping in the reported family, combined with whole exome sequencing in one affected infant, we identified a homozygous splice site mutation g.IVS8+1G>A in cyclin-dependent kinase 5 (CDK5), causing complete skipping of exon 8, and leading to a frame shift and premature stop codon (p.V162SfsX19). The mutation co-segregated with the disease phenotype in all 29 study participants (4 patients and 25 healthy relatives), and was not identified in 200 ethnically matched control chromosomes. The p.V162SfsX19 mutation causes lack of endogenous CDK5 expression in affected dermal fibroblasts and brain tissue at the mRNA and protein levels, consistent with nonsense-mediated mRNA decay. Functional analysis of the p.V162SfsX19 mutation, using a yeast complementation assay, showed loss-of-function of the mutant CDK5 gene product, thereby implicating its role in the pathogenesis of autosomal recessive LCH in the studied family.
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- 2015
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24. Erratum to: Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with a loss-of-function mutation in CDK5.
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Magen D, Ofir A, Berger L, Goldsher D, Eran A, Katib N, Nijem Y, Vlodavsky E, Tzur S, Behar DM, Fellig Y, and Mandel H
- Published
- 2015
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25. Previously unrecognized pattern of central nervous system hemangiopericytoma with pseudoglandular spaces.
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Pekmezci M, Vlodavsky E, and Perry A
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- Blister pathology, Brain Neoplasms surgery, Diagnosis, Differential, Epithelioid Cells pathology, Female, Hemangiopericytoma surgery, Humans, Middle Aged, Brain pathology, Brain Neoplasms pathology, Hemangiopericytoma pathology, Magnetic Resonance Imaging
- Abstract
Central nervous system hemangiopericytoma (HPC) is an uncommon extraaxial tumor with controversial terminology, histogenesis, and grading. Herein, we report a unique example in a 64-year-old woman with a 3.2 cm extra-axial right frontal lobe mass. Histologic sections showed an HPC with increased mitotic activity and elevated proliferation index, interspersed with gland-like spaces lined by epithelioid cells with apical blebs and filled with proteinaceous material. Both spindled and epithelioid cells expressed BCL-2, CD99, and nuclear STAT6, but were negative for CD34, AE1/AE3, CAM5.2, and epithelial membrane antigen. A diagnosis of anaplastic HPC with pseudoglandular spaces was rendered. To our knowledge, this is the first pathologically and molecularly well-documented example in the literature. This pattern has only been reported once in 1983 and is not widely known. Differential diagnosis included synovial sarcoma, anaplastic meningioma with epithelial metaplasia, malignant peripheral nerve sheath tumor, and metastatic carcinosarcoma. Accurate diagnosis depends on recognition of this pattern, along with appropriate immunohistochemical and molecular work-up.
- Published
- 2014
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26. Alkaline phosphatase level change in patients with osteosarcoma: its role as a predictive factor of tumor necrosis and clinical outcome.
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Khoury JF, Ben-Arush MW, Weintraub M, Waldman E, Futerman B, Vlodavsky E, and Postovsky S
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- Adolescent, Child, Female, Follow-Up Studies, Humans, Male, Necrosis pathology, Neoplasm Metastasis, Osteosarcoma drug therapy, Prognosis, Retrospective Studies, Sex Factors, Survival Rate, Treatment Outcome, Young Adult, Alkaline Phosphatase metabolism, Antineoplastic Agents therapeutic use, Neoadjuvant Therapy methods, Osteosarcoma pathology
- Abstract
Background: In osteosarcoma the histological response, measured by the percentage of tumor necrosis, constitutes one of the most significant predictive factors, with better survival in patients whose tumor necrosis is > or = 90%., Objectives: To determine if the decrease rate of serum alkaline phosphatase (SAP) levels during the first month of neoadjuvant chemotherapy could serve as a predictive indicator of tumor necrosis and clinical outcome., Methods: We analyzed the medical files of 53 osteosarcoma patients (19 females, 34 males) (median age 16 years, range 8-24); the disease was metastatic in 12 and localized in the other 41., Results: The histological responses were good in 38 patients (71.7%) and poor in 15 (28.3%). At a median follow-up of 50 months, 34 patients (64.2%) had no evidence of disease and 19 (35.8%) had died from the disease. High levels of SAP at diagnosis correlated with worse survival (P = 0.002). There was no difference in overall survival between patients whose SAP decrease rate was > 25% and those with a rate < 25% (P = 0.14). Among female patients, "rapid" SAP responders had better survival than "slow" responders (P= 0.026). In patients with metastases the SAP decrease rate was positively correlated with survival (P = 0.042)., Conclusions: There was no evidence that "rapid" SAP responders had a higher percentage of tumor necrosis than "slow" responders, although female "rapid" SAP responders had a better prognosis than "slow" responders. Patients with metastases at presentation and "rapid" SAP response had better prognoses.
- Published
- 2014
27. Involvement of the mitochondrial benzodiazepine receptor in traumatic brain injury: therapeutic implications.
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Vlodavsky E, Palzur E, and Soustiel JF
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- Animals, Brain Injuries drug therapy, Humans, Mitochondria drug effects, Brain Injuries metabolism, Mitochondria metabolism, Receptors, GABA-A metabolism
- Abstract
Traumatic brain injuries represent the leading cause of death and morbidity in young adults in western countries, and are responsible for a major social and economical burden. For decades, the mainstay of neurotrauma management has been represented by control of post-traumatic edema. With the emergence of a better understanding of the underlying cellular mechanisms responsible for the generation of secondary brain damage, the hope for the "magic bullet" has prompted the development of novel drugs that have repeatedly failed to significantly improve outcome of head-injured patients. During the past decade, mitochondrial functional and structural impairment has emerged as a pivotal event in the pathway of cell to secondary death. Extensive research has identified a vast range of deleterious signals that are generated and integrated at the mitochondrial level resulting in impairment of major mitochondrial functions such as calcium homeostasis, free radicals generation and detoxification, energy production and neurosteroidogenesis. Mitochondria have therefore emerged as a potential therapeutic target. Within the spectrum of major mitochondrial structural components, the 18 kDa translocator protein (TSPO) has shown important and relevant functions such as steroid synthesis and modulation of the mitochondrial permeability transition that may substantially affect the fate of injured cells. This review summarizes the potential therapeutic implications of TSPO modulation in traumatic brain injury in the view of the current knowledge on this intriguing mitochondrial complex.
- Published
- 2014
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28. KRAS mutation positive mucinous adenocarcinoma originating in mature ovarian teratoma: case report and review of literature.
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Hershkovitz D, Vlodavsky E, Simon E, and Ben-Izhak O
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- Adenocarcinoma, Mucinous metabolism, Adenocarcinoma, Mucinous pathology, Adolescent, Female, Humans, Neoplasms, Second Primary metabolism, Neoplasms, Second Primary pathology, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Proto-Oncogene Proteins p21(ras), Teratoma metabolism, Teratoma pathology, Adenocarcinoma, Mucinous genetics, Mutation, Neoplasms, Second Primary genetics, Ovarian Neoplasms genetics, Proto-Oncogene Proteins genetics, Teratoma genetics, ras Proteins genetics
- Abstract
Mature ovarian teratomas rarely undergo transformation into malignancy. Carcinomas, mostly squamous cell carcinoma, are the most common malignancy arising in mature cystic teratoma. In the present report we describe a 13-year-old girl who developed a large mass in her ovary. Fine needle biopsy identified intestinal type mucinous adenocarcinoma, which was also identified in the full surgical specimen. Extensive sampling of the surgical specimen also identified areas of mature cystic teratoma. Interestingly, molecular analysis of DNA extracted from various components of the lesion identified KRAS mutation in the carcinoma, borderline mucinous tumor and benign intestinal-type epithelium but not in the epidermal component of the teratoma. To the best of our knowledge this is the first report of KRAS mutation in mucinous carcinoma originating in mature cystic teratoma. We discuss the importance of extensive tissue sampling to differentiate between carcinoma originating in teratoma and metastatic colorectal carcinoma to the ovary. Additionally, the identification of KRAS mutation in the morphologically benign intestinal-type epithelium indicated that it is an early event in the carcinogenic sequence and that the molecular pathway of carcinogenesis in teratoma is similar to that in the carcinogenic process of somatic tissue., (© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)
- Published
- 2013
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29. Association between esophageal leiomyomatosis and p53 mutation.
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Kazarin O, Vlodavsky E, Guralnik L, Kremer R, Lachter J, and Bar-Sela G
- Subjects
- Biopsy, DNA Mutational Analysis, Endoscopy, Gastrointestinal, Esophageal Neoplasms diagnosis, Female, Humans, Leiomyomatosis diagnosis, Middle Aged, Tomography, X-Ray Computed, DNA, Neoplasm genetics, Esophageal Neoplasms genetics, Esophagus pathology, Genes, p53 genetics, Leiomyomatosis genetics, Mutation
- Abstract
Li-Fraumeni syndrome is a cancer predisposition syndrome associated with a variety of neoplasms, mainly soft tissue sarcoma, premenopausal breast cancer, brain tumors, adrenocortical carcinoma, and leukemia. Esophageal leiomyomatosis involves the presence of several rare benign neoplastic lesions composed of proliferating smooth muscle cells in the esophageal wall. The current case report presents a patient with recurrent diffuse leiomyomas of the esophagus and confirmed p53 mutation with clinical criteria of Li-Fraumenilike syndrome., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
30. [Rapidly vanishing hip--a mystery].
- Author
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Keren Y, Sigal A, Greental A, Vlodavsky E, Soudry M, and Militianu D
- Subjects
- Acute Pain etiology, Aged, Disease Progression, Female, Humans, Femur Head pathology, Hip Joint pathology, Joint Diseases pathology
- Abstract
Rapidly destructive hip disease is a rare condition, the cause of which is yet to be clarified, and is described in the literature by scant case reports. The disease was first described by Forestier in 1957, and since then many names have been proposed to describe the rapid vanishing of the femoral head, and occasionally the acetabulum. This condition initially represents as acute hip pain, and rapidly progresses to complete vanishing of the proximal femur, within a few months. We briefly discuss the literature regarding this phenomenon, and describe a case of a female patient who suffered from complete disappearance of the femoral head within 9 weeks.
- Published
- 2013
31. Primitive neuroectodermal tumor of the kidney with renal failure.
- Author
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Gefen A, Arush MW, Eisenstein I, Vlodavsky E, Abdah-Bortnyak R, and Postovsky S
- Subjects
- Adolescent, Female, Humans, Kidney Neoplasms pathology, Neuroectodermal Tumors, Primitive pathology, Kidney Neoplasms complications, Neuroectodermal Tumors, Primitive complications, Renal Insufficiency etiology
- Published
- 2012
32. Autoimmune pancreatitis misdiagnosed as a tumor of the head of the pancreas.
- Author
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Brauner E, Lachter J, Ben-Ishay O, Vlodavsky E, and Kluger Y
- Abstract
Autoimmune pancreatitis can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. Differentiating between those two entities requires implementation of clinical judgment and experience along with objective parameters that may suggest either condition. Few strategies have been proposed for the surgeon to implement when facing borderline cases. The following case is an example of a clinical scenario compatible with an accepted algorithm for diagnosis of pancreatic cancer, which eventually proved wrong. We present a 75-year-old patient who was admitted for obstructive jaundice. Imaging features were highly suggestive for pancreatic cancer as was the carbohydrate antigen 19-9 (CA 19-9) level, leading to a decision for surgery. Pathological examination revealed autoimmune pancreatitis. Though no frank carcinoma was found, premalignant ductal changes of pancreatic intraepithelial neoplasia (PanIN) I and PanIN II were discovered throughout the pancreatic duct. Caution is advised when relying on the combination of highly suggestive radiology features and elevated levels of CA 19-9 in the diagnosis of pancreatic cancer. When the tissue diagnosis is not conclusive, obtaining IgG4 and antinuclear Ab levels is advised, to rule out the rare possibility of autoimmune pancreatitis. Patients with autoimmune pancreatitis should be followed carefully as precancerous lesions may accompany the benign disease and the correlation of these two entities has not been ruled out.
- Published
- 2012
- Full Text
- View/download PDF
33. Anaplastic ganglioglioma in the spinal cord: case report and literature review.
- Author
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Kuten J, Kaidar-Person O, Vlodavsky E, Postovsky S, Billan S, Kuten A, and Bortnyak-Abdah R
- Subjects
- Adolescent, Female, Humans, Cervical Vertebrae, Ganglioglioma diagnosis, Ganglioglioma surgery, Spinal Cord Neoplasms diagnosis, Spinal Cord Neoplasms surgery
- Abstract
Anaplastic ganglioglioma (AGG) is a rare tumor. A PubMed database search yielded only a few case reports and fewer case series. An even rarer entity is AGG arising in the spinal cord. We present a case of a pediatric patient with a pathological diagnosis of spinal AGG., (Copyright © 2013 S. Karger AG, Basel.)
- Published
- 2012
- Full Text
- View/download PDF
34. Improvement of cerebral metabolism mediated by Ro5-4864 is associated with relief of intracranial pressure and mitochondrial protective effect in experimental brain injury.
- Author
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Soustiel JF, Vlodavsky E, Milman F, Gavish M, and Zaaroor M
- Subjects
- Animals, Benzodiazepinones therapeutic use, Brain metabolism, Brain pathology, Brain Edema, Brain Injuries pathology, Brain Injuries physiopathology, Cerebral Cortex drug effects, Cerebral Cortex pathology, Cerebrovascular Circulation drug effects, Disease Models, Animal, Intracranial Pressure physiology, Male, Microdialysis, Mitochondria metabolism, Mitochondria pathology, Neurologic Examination drug effects, Protective Agents therapeutic use, Random Allocation, Rats, Rats, Sprague-Dawley, Benzodiazepinones pharmacology, Brain Injuries metabolism, Cerebral Cortex metabolism, Intracranial Pressure drug effects, Mitochondria drug effects, Protective Agents pharmacology
- Abstract
Purpose: To investigate the possible impact of reduction of mitochondrial membrane permeabilization by modulation of the 18 kDa translocator protein mediated by Ro5-4864 over post-traumatic cerebral edema and metabolic crisis., Methods: Cerebral microdialysis and intracranial pressure (ICP) monitoring were performed in Sprague-Dawley rats treated by intraperitoneal injection of either dimethylsulfoxide (vehicle) or Ro5-4864 following cortical contusion and further correlated with quantitative assessment of mitochondrial damage, water content in the injured tissue, modified neurological severity score, and lesion size., Results: Ro5-4864 resulted in a profound decrease in ICP that correlated with improved cerebral metabolism characterized by significantly higher glucose and pyruvate and lower lactate concentrations in the pericontusional area in comparison with vehicle-treated animals. Reduced ICP correlated with reduced water content in the injured tissue; improved metabolism was associated with reduced mitochondrial damage evidenced by electron microscopy. Both effects were associated with a profound and significant reduction in glycerol release and lesion size, and correlated with improved neurological recovery., Conclusions: The present study shows that Ro5-4864 has a favorable effect on the fate of injured brain, presumably mediated by improvement of metabolism. It further suggests that improvement of metabolism may contribute to ICP relief.
- Published
- 2011
- Full Text
- View/download PDF
35. Computerized morphometry as an aid in distinguishing recurrent versus nonrecurrent meningiomas.
- Author
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Noy S, Vlodavsky E, Klorin G, Drumea K, Ben Izhak O, Shor E, and Sabo E
- Subjects
- Aged, Algorithms, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local diagnosis, Prognosis, Meningeal Neoplasms diagnosis, Meningioma diagnosis
- Abstract
Objective: To use novel digital and morphometric methods to identify variables able to better predict the recurrence of intracranial meningiomas., Study Design: Histologic images from 30 previously diagnosed meningioma tumors that recurred over 10 years of follow-up were consecutively selected from the Rambam Pathology Archives. Images were captured and morphometrically analyzed. Novel algorithms of digital pattern recognition using Fourier transformation and fractal and nuclear texture analyses were applied to evaluate the overall growth pattern complexity of the tumors, as well as the chromatin texture of individual tumor nuclei. The extracted parameters were then correlated with patient prognosis., Results: Kaplan-Meier analyses revealed statistically significant associations between tumor morphometric parameters and recurrence times. Tumors with less nuclear orientation, more nuclear density, higher fractal dimension, and less regular chromatin textures tended to recur faster than those with a higher degree of nuclear order, less pattern complexity, lower density, and more homogeneous chromatin nuclear textures (p < 0.01)., Conclusion: To our knowledge, these digital morphometric methods were used for the first time to accurately predict tumor recurrence in patients with intracranial meningiomas. The use of these methods may bring additional valuable information to the clinician regarding the optimal management of these patients.
- Published
- 2011
36. Colon and lung choriocarcinoma.
- Author
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Froylich D, Shiloni E, Lavie O, Neumann A, Vlodavsky E, and Hazzan D
- Subjects
- Choriocarcinoma, Non-gestational therapy, Colonic Neoplasms therapy, Female, Humans, Lung Neoplasms therapy, Middle Aged, Choriocarcinoma, Non-gestational pathology, Colonic Neoplasms pathology, Lung Neoplasms pathology
- Published
- 2010
37. Undifferentiated sarcoma of the thyroid in a child.
- Author
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Postovsky S, Vlodavsky E, Kuten A, Shendler Y, Doweck I, and Ben Arush MW
- Subjects
- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Dactinomycin administration & dosage, Doxorubicin administration & dosage, Female, Humans, Ifosfamide administration & dosage, Immunohistochemistry, Radiotherapy, Thyroidectomy, Vincristine administration & dosage, Sarcoma pathology, Sarcoma therapy, Thyroid Neoplasms pathology, Thyroid Neoplasms therapy
- Abstract
The most common malignant tumor of the thyroid is papillary carcinoma. Sarcoma of the thyroid is encountered very rarely; its therapy is complex and poses significant problems due to the problematic location of the tumor. A 14-year-old female was diagnosed with undifferentiated sarcoma of the thyroid and received combined therapy comprising surgery, chemo- and radiotherapy without significant side effects. This case underlines the fact that undifferentiated thyroid sarcoma may be a diagnostic possibility in children with malignant masses of the neck and may be successfully treated with modern therapeutic strategies., (Copyright 2010 Wiley-Liss, Inc.)
- Published
- 2010
- Full Text
- View/download PDF
38. Primary cardiac chondrosarcoma with rapid MFH-like recurrence: case report and review of tumor type.
- Author
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Sawaed S, Adler AC, Vlodavsky E, and Bar-Sela G
- Subjects
- Chemotherapy, Adjuvant, Chondrosarcoma diagnostic imaging, Chondrosarcoma secondary, Diagnosis, Differential, Echocardiography, Heart Neoplasms diagnostic imaging, Heart Neoplasms pathology, Histiocytoma, Malignant Fibrous diagnosis, Humans, Male, Young Adult, Bone Neoplasms secondary, Chondrosarcoma diagnosis, Chondrosarcoma surgery, Heart Neoplasms diagnosis, Heart Neoplasms surgery
- Abstract
We present a case report of a patient with a rare primary cardiac tumor, chondrosarcoma. After initial excision, a locally advanced recurrence appeared within six weeks at a different site in the heart with the histological features of a high-grade sarcoma. We discuss the background, management and prognosis of these rare tumors.
- Published
- 2010
- Full Text
- View/download PDF
39. Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association?
- Author
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Bacri D, Arush MW, Vlodavsky E, Kollander Y, Militianu D, and Postovsky S
- Subjects
- Adolescent, Alkaline Phosphatase blood, Bone Neoplasms blood, Bone Neoplasms drug therapy, Bone Remodeling, Humans, Male, Mutation, Osteosarcoma blood, Osteosarcoma drug therapy, Bone Neoplasms genetics, Osteolysis genetics, Osteosarcoma genetics, Receptor Activator of Nuclear Factor-kappa B genetics
- Abstract
We present the first reported case of a child with familial expansile osteolysis syndrome (FEO) who developed osteogenic sarcoma (OS) of the iliac bone. A 17-year-old adolescent presented with pain and a mass on the left pelvis. He was from a family with several members who had been diagnosed with FEO, from which he also suffered. The median life expectancy of affected members of the family was reported as 25 to 30 years, with death ensuing as a result of various respiratory and cardiac complications of severe skeletal deformations, characteristic of increased bone turnover as seen in FEO. Biopsy of the patient's mass revealed chondroblastic OS. He was treated according to the P9754 protocol for patients with newly diagnosed nonmetastatic OS. Chemotherapy consisted of HD-MTX, ifosfomide, doxorubicin, and cisplatin. Complete resection of the tumor was carried out, but the patient subsequently developed metastatic disease and died (histologic response to neoadjuvant chemotherapy-85%). The patient's alkaline phosphatase level that was highly elevated before the start of chemotherapy, dropped significantly during treatment, with repeated elevation soon after definitive surgery, while he was recuperating and not on treatment. We speculate that chemotherapy affected not only the malignant cells of OS but normal osteoblasts as well, with a decreasing level of alkaline phosphatase even in the absence of any clinical and radiographic signs of OS. We also think that increased bone turnover, characteristic of a condition such as FEO, may facilitate de novo development of OS.
- Published
- 2010
- Full Text
- View/download PDF
40. Rectal bleeding as a presenting symptom of AL amyloidosis and multiple myeloma.
- Author
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Maza I, Vlodavsky E, and Eliakim RA
- Abstract
Amyloidosis of the gastrointestinal tract is a rare disease that presents with common, nonspecific signs and symptoms. It may affect any part of the gastrointestinal tract from mouth to anus. The clinical and endoscopic features are diverse and may mimic other diseases, such as inflammatory bowel disease, malignancy, ischemic colitis and, at times, collagenous colitis. We describe an uncommon case of rectal bleeding and anemia with polypoid lesions and ulcerations in the colon, as the presenting symptom of AL amyloidosis and light chain multiple myeloma.
- Published
- 2010
- Full Text
- View/download PDF
41. Lytic bone lesion: presenting finding of sarcoidosis.
- Author
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Hamoud S, Srour S, Fruchter O, Vlodavsky E, and Hayek T
- Subjects
- Female, Humans, Middle Aged, Osteolysis diagnosis, Osteolysis therapy, Sarcoidosis therapy, Osteolysis etiology, Sarcoidosis complications, Sarcoidosis diagnosis, Skull
- Published
- 2010
42. Ovarian adrenal rest tumor in a congenital adrenal hyperplasia patient with adrenocorticotropin hypersecretion following adrenalectomy.
- Author
-
Tiosano D, Vlodavsky E, Filmar S, Weiner Z, Goldsher D, and Bar-Shalom R
- Subjects
- Adolescent, Adrenal Hyperplasia, Congenital blood, Adrenal Hyperplasia, Congenital surgery, Adrenal Rest Tumor blood, Adrenalectomy, Adrenocorticotropic Hormone blood, Female, Humans, Ovarian Neoplasms blood, Adrenal Hyperplasia, Congenital complications, Adrenal Rest Tumor complications, Nelson Syndrome blood, Ovarian Neoplasms complications
- Abstract
Objective: Ovarian adrenal rest tumors (OARTs) are rare in contrast to testicular adrenal rest tumors. We report a case of OART in a patient with congenital adrenal hyperplasia who developed Nelson's syndrome after bilateral adrenalectomy., Methods: We describe the clinical, imaging, and laboratory findings of the patient and review the relevant literature regarding OART and the possible interaction between ACTH and brown adipose tissue., Results: An 18-year-old female with congenital adrenal hyperplasia, who had undergone bilateral adrenalectomy at the age of 10 years, presented with severe hyperpigmentation and hirsutism. Rectal ultrasonography showed a mass in the right ovary. (18)F-fluorodeoxyglucose PET/CT revealed intense uptake both in this mass and in brown adipose tissue located in typical supradiaphragmatic sites. Laparoscopic removal of the ovarian mass confirmed the diagnosis of OART. A systematic review revealed 9 documented cases of OART. As in our case, all presented with elevated ACTH levels., Conclusions: Common to all documented cases of OART are sustained high ACTH levels that activate the adrenal anlagen tissue in the ovaries., (2010 S. Karger AG, Basel.)
- Published
- 2010
- Full Text
- View/download PDF
43. Plasma heparanase as a significant marker of treatment response in children with Hodgkin lymphoma: pilot study.
- Author
-
Ben Arush MW, Shafat I, Ben Barak A, Shalom RB, Vlodavsky I, and Ilan N
- Subjects
- Adolescent, Child, Child, Preschool, Female, Hodgkin Disease drug therapy, Humans, Male, Neoplasm Staging, Pilot Projects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor blood, Glucuronidase blood, Hodgkin Disease blood, Hodgkin Disease diagnosis
- Abstract
Introduction: The aim of this pilot study was to determine heparanase plasma levels (HP) at diagnosis and at restaging in children diagnosed with Hodgkin lymphoma and to investigate whether this parameter provides prognostic information for response to treatment after induction therapy., Patients and Methods: HP levels of 19 pediatric patients (mean age: 10.3 years (y) (range, 4-18 y), 9 girls, 10 boys) with Hodgkin lymphoma were assayed at diagnosis and at restaging. HP levels were determined using an ELISA anti-human heparanase immunoassay kit. According to diagnosis, CAT scan and/or FDG/ PET-CT fusion were performed to assess response to treatment after 2-3 courses of chemotherapy. Two patients received VAMP protocol (1 stage IA, 1 stage IIA), 1 received AV-PC (nonbulky stage IIA), 4 received COPP/ABV (3 stage IIA bulky, 1 stage IIIA nonbulky), 4 received ABVE-PC (2 stage IIB, 1 stage IIA bulky, 1 stage IIIA bulky), 2 received ABVD (1 stage IIA bulky, 1 stage IIIA), and 6 received escalated BEACOPP (1 stage IIIB, 3 stage IVA, 2 stage IVB)., Results: Changes in HP levels were found to correlate with response to treatment for most of the children. At diagnosis, average HP level was 1019 pg/mL (range, 141-5733 pg/mL), decreasing at restaging to 588 pg/mL (range, 62-3267 pg/mL) (p = .034). At diagnosis, the average HP of the 16 patients in CR or VGPR was 1104 pg/mL; it had decreased at restaging to 586 pg/mL (p = .032). At diagnosis, the average HP level for the 3 patients with TP or PR was 1704 pg/mL; it had increased to 1938 pg/mL at restaging (p = .166). Due to the small number of patients, no correlation was observed between HP levels at diagnosis, staging, or any other clinical prognostic factor., Conclusions: Changes in plasma HP levels correlated with response to treatment for children diagnosed with Hodgkin lymphoma. This provides a rationale for exploring clinical interest in plasma heparanase measurements of a larger group, using the test for clinical trials of antiangiogenic therapies.
- Published
- 2009
- Full Text
- View/download PDF
44. The role of advanced MR methods in the diagnosis of cerebral amyloidoma.
- Author
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Nossek E, Bashat DB, Artzi M, Rosenberg K, Lichter I, Shtern O, Ami HB, Aizenstein O, Vlodavsky E, Constantinescu M, and Ram Z
- Subjects
- Amyloidosis pathology, Biopsy, Brain Diseases pathology, Female, Humans, Middle Aged, Amyloidosis diagnosis, Brain Diseases diagnosis, Magnetic Resonance Imaging methods
- Abstract
Amyloidoma is a term referring to a tumor-like deposition of extracellular insoluble fibrillar protein. Tumor-like amyloid formation in the brain had been described in isolated cases. However no advanced radiological studies to characterize these lesions have been reported. In the report, we have describe a 59-year-old woman, presented several months prior to diagnosis with memory decline, dizziness, walking instability, and speech difficulties. MRI revealed a left basal ganglia lesion with an intraventricular component. The patient underwent a stereotactic biopsy, which confirmed the diagnosis of amyloidoma, an extensive radiographic characterization of amyloidoma using advanced MR techniques was done, including magnetic resonance spectroscopy, dynamic susceptibility contrast, susceptibility weighted image (SWI), and magnetization transfer (MTR). All advanced MR techniques were able to characterize the amyloidoma as a non-neoplastic process. This is an example where such methods can be used for differential diagnosis of atypical brain lesions.
- Published
- 2009
- Full Text
- View/download PDF
45. Neuroprotective effect of Ro5-4864 following brain injury.
- Author
-
Soustiel JF, Zaaroor M, Vlodavsky E, Veenman L, Weizman A, and Gavish M
- Subjects
- Animals, Antineoplastic Agents metabolism, Antineoplastic Agents pharmacology, Apoptosis drug effects, Benzodiazepinones metabolism, Carrier Proteins metabolism, Caspases metabolism, Convulsants metabolism, Convulsants pharmacology, Disease Models, Animal, Isoquinolines metabolism, Isoquinolines pharmacology, Ligands, Male, Membrane Potential, Mitochondrial drug effects, Mitochondria metabolism, Neurons pathology, Neuroprotective Agents metabolism, Rats, Rats, Sprague-Dawley, Receptors, GABA-A metabolism, Benzodiazepinones pharmacology, Brain Injuries drug therapy, Brain Injuries pathology, Neuroprotective Agents pharmacology
- Abstract
The 18 kDa translocator protein (TSPO) is a protein complex located at the outer mitochondrial membrane and interacting with the mitochondrial permeability transition pore (mPTP), indicating its involvement in the control of mPTP opening. We intended to explore the effect of TSPO ligands, PK 11195 and Ro5-4864 on apoptosis in a rat model of cortical injury. Sprague-Dawley rats received a daily intraperitoneal injection of dimethylsulfoxide (vehicle), PK 11195, or Ro5-4864, starting 2 days prior the injury and a third injection after the injury. At 6 weeks, immunohistochemistry analysis showed that Ro5-4864 resulted in a significant increase in the number of surviving neurons and in the density of the neurofilament network in the perilesional cortex in comparison with animals of the vehicle and PK 11195 groups. In tissue samples dissected from the injured area, Ro5-4864 caused a significant reduction in activation of caspases 3 and 9 but not of caspase 8 in comparison with the vehicle and PK 11195 groups. In addition, measurements of transmembrane mitochondrial potential of mitochondria (Deltapsi(M)) isolated from normal rat brain showed that loss of Deltapsi(M) induced by recombinant Bax could be significantly reduced by Ro5-4864 in a concentration-dependent manner. Our findings indicate that the neuroprotective effect shown by Ro5-4864 in the present model of brain injury involves the mitochondrial pathway of apoptosis modulation of mPTP.
- Published
- 2008
- Full Text
- View/download PDF
46. Neuroprotective effect of hyperbaric oxygen therapy in brain injury is mediated by preservation of mitochondrial membrane properties.
- Author
-
Palzur E, Zaaroor M, Vlodavsky E, Milman F, and Soustiel JF
- Subjects
- Animals, Axons metabolism, Brain Injuries physiopathology, Caspases metabolism, Dendrites metabolism, Disease Models, Animal, Energy Metabolism physiology, Male, Oxygen Consumption physiology, Parietal Lobe metabolism, Parietal Lobe physiopathology, Rats, Rats, Sprague-Dawley, Apoptosis physiology, Brain Injuries metabolism, Brain Injuries therapy, Hyperbaric Oxygenation methods, Membrane Potential, Mitochondrial physiology, Mitochondrial Membranes metabolism
- Abstract
Recent experimental data have shown that hyperbaric oxygen therapy (HBOT) was associated increased Bcl-2 expression at the injury site that correlated with reduced apoptosis. We hypothesized that HBOT mediated enhancement of Bcl-2 expression and increased intracellular oxygen bio-availability may both contribute to preserve mitochondrial integrity and reduce the activation of the mitochondrial pathway of apoptosis. For this purpose, a cortical lesion was created in the parietal cortex of Sprague-Dawley rats by dynamic cortical deformation (DCD) and outcome measures in non-treated animals were compared with that of HBOT treated rats. Morphological analysis showed a profound reduction in neuronal counts in the perilesional area and a marked rarefaction of the density of the axonal-dendritic network. In treated animals, however, there was a significant attenuation of the impact of DCD over perilesional neurons, characterized by significantly higher cell counts and denser axonal network. In mitochondria isolated from injured brain tissue, there was a profound loss of mitochondrial transmembrane potential (Deltapsi(M)) that proved to be substantially reversed by HBOT. This finding correlated with a significant reduction of caspases 3 and 9 activation in HBOT treated animals but not of caspase 8, indicating a selective effect over the intrinsic pathway of apoptosis. All together, our results indicate that the neuroprotective effect of HBOT may represent the consequence of preserved mitochondrial integrity and subsequent inhibition of the mPTP and reduction of the mitochondrial pathway of apoptosis.
- Published
- 2008
- Full Text
- View/download PDF
47. Ultrasound imaging of fasciitis due to body-building supplement.
- Author
-
Rozin AP, Schapira D, Braun-Moscovici Y, Markovits D, Vlodavsky E, and Balbir-Gurman A
- Subjects
- Adrenal Cortex Hormones therapeutic use, Adult, Fasciitis chemically induced, Fasciitis drug therapy, Humans, Male, Treatment Outcome, Tryptophan administration & dosage, Ultrasonography, Dietary Supplements, Fasciitis diagnostic imaging, Tryptophan adverse effects
- Abstract
Background: Fascia and soft tissues, rich in collagen, receptors of pain and capable of significant distention, may be targets of autoimmune inflammatory diseases. We observed fasciitis due to the protein supplement Pure Whey, which has not been reported previously., Methods: Sonography (Sonosite-Titan, 5 to 10 MHz, L-38) was performed on a patient (age, 26 years; body mass index, 38 kg/m2) with protein fasciitis. He had developed compact swelling of his forearms, hands, and legs, with skin irregularity and severe disability (without peripheral eosinophilia, normal Ig and ESR 18/hr) after taking Pure Whey, containing L-tryptophan (1.4 g per 100 g of protein). A deep skin biopsy was performed. The thickness of the brachioradial fascia (BRF) was measured and compared with 10 healthy control subjects (men ages 36.7 +/- 8.3 years; body mass index, 26.4 +/- 6.5 kg/m2)., Results: The deep skin biopsy showed severe fat interlobular and fascial thickening with mononuclear (noneosinophilic) infiltrate and fibrosis associated with fasciitis. BRF of the 10 healthy men had a thickness of 0.75 +/- 0.19 mm, compared with the patient's 2.4 mm thickened and cleaved BRF. After 2.5 months of corticosteroid therapy (30 mg/d with tapering) and discontinuation of the protein supplement, the patient's BRF returned to a monolayer appearance. Its thickness reduced to normal (0.8 mm), with significant clinical improvement., Conclusions: This case of noneosinophilic fasciitis associated with ingestion of L-tryptophan-containing protein supplement responded favorably to corticosteroid therapy. Sonography proved to be an effective method to visualize and confirm the fasciitis and to follow the course and therapy.
- Published
- 2008
- Full Text
- View/download PDF
48. Ivory fingers: monostotic Paget's disease of the phalanges.
- Author
-
Calif E, Vlodavsky E, and Stahl S
- Subjects
- Adult, Female, Humans, Middle Aged, Radiography, Radionuclide Imaging, Radiopharmaceuticals, Technetium Tc 99m Medronate, Fingers diagnostic imaging, Osteitis Deformans diagnostic imaging
- Published
- 2007
- Full Text
- View/download PDF
49. Imaging features of posterior mediastinal chordoma in a child.
- Author
-
Soudack M, Guralnik L, Ben-Nun A, Berkowitz D, Postovsky S, Vlodavsky E, and Engel A
- Subjects
- Child, Preschool, Chordoma surgery, Cough etiology, Diagnosis, Differential, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Mediastinal Neoplasms surgery, Mediastinum pathology, Mediastinum surgery, Respiratory Sounds, Tomography, X-Ray Computed, Chordoma diagnosis, Mediastinal Neoplasms diagnosis, Mediastinum diagnostic imaging, Neoplasm Recurrence, Local diagnosis
- Abstract
A 5 1/2-year-old boy presented with repeated episodes of stridor and cough. Chest radiography demonstrated a widened mediastinum. Evaluation by CT revealed a low-density posterior mediastinal mass initially diagnosed as benign tumor. Histopathological analysis of the resected mass disclosed a malignant chordoma. Our radiological results are described with an analysis of the imaging findings in the medical literature. We present our suggestions for preoperative evaluation of posterior mediastinal tumors.
- Published
- 2007
- Full Text
- View/download PDF
50. Secondary glioblastoma multiforme after treatment for primary choroid plexus carcinoma in childhood.
- Author
-
Postovsky S, Vlodavsky E, Eran A, Guilburd J, and Ben Arush MW
- Subjects
- Adolescent, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Carboplatin administration & dosage, Choroid Plexus Neoplasms therapy, Cisplatin administration & dosage, Combined Modality Therapy, Diagnosis, Differential, Etoposide administration & dosage, Fatal Outcome, Glioblastoma etiology, Glioblastoma therapy, Humans, Male, Neoplasms, Second Primary etiology, Neoplasms, Second Primary therapy, Vincristine administration & dosage, Choroid Plexus Neoplasms pathology, Glioblastoma pathology, Neoplasms, Second Primary pathology
- Abstract
A 15-year-old boy was diagnosed with choroid plexus carcinoma (CPC) of the right lateral ventricle. His metastatic work-up was negative. After complete macroscopic resection of the tumor, the patient was treated with chemotherapy consisting of vincristine, cisplatin, etoposide, and carboplatin, followed by radiotherapy for a total dose of 34.2 Gy on the whole craniospinal axis plus a boost of 19.8 Gy at the tumor region. The patient remained in complete clinical and radiologic remission over the next 5 years when a secondary malignant tumor, glioblastoma multiforme, a rare complication of the treatment of CPC, was diagnosed. This case reflects the necessity of thorough follow-up in long-term survivors of CPC.
- Published
- 2007
- Full Text
- View/download PDF
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