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https://www.readbyqxmd.com/read/27792997/cd99-polymorphisms-significantly-influence-the-probability-to-develop-ewing-sarcoma-in-earlier-age-and-patient-disease-progression
#1
Marcella Martinelli, Alessandro Parra, Luca Scapoli, Paola De Sanctis, Valentina Chiadini, Claudia Hattinger, Piero Picci, Cinzia Zucchini, Katia Scotlandi
Ewing sarcoma (EWS), the second most common primary bone tumor in pediatric age, is known for its paucity of recurrent somatic abnormalities. Apart from the chimeric oncoprotein that derives from the fusion of EWS and FLI genes, recent genome-wide association studies have identified susceptibility variants near the EGR2 gene that regulate DNA binding of EWS-FLI. However, to induce transformation, EWS-FLI requires the presence of additional molecular events, including the expression of CD99, a cell surface molecule with critical relevance for the pathogenesis of EWS...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27752884/factors-affecting-survival-outcomes-of-patients-with-non-metastatic-ewing-s-sarcoma-family-tumors-in-the-spine-a-retrospective-analysis-of-63-patients-in-a-single-center
#2
Wei Wan, Yan Lou, Zhiqi Hu, Ting Wang, Jinsong Li, Yu Tang, Zhipeng Wu, Leqin Xu, Xinghai Yang, Dianwen Song, Jianru Xiao
Little information has been published in the literature regarding survival outcomes of patients with Ewing's sarcoma family tumors (ESFTs) of the spine. The purpose of this study is to explore factors that may affect the prognosis of patients with non-metastatic spinal ESFTs. A retrospective analysis of survival outcomes was performed in patients with non-metastatic spinal ESFTs. Univariate and multivariate analyses were employed to identify prognostic factors for recurrence and survival. Recurrence-free survival (RFS) and overall survival (OS) were defined as the date of surgery to the date of local relapse and death...
October 17, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27696711/ewing-sarcoma-family-of-tumors-in-children-younger-than-10-years-of-age
#3
Winston W Huh, Najat C Daw, Cynthia E Herzog, Mark F Munsell, Mary Frances McAleer, Valerae O Lewis
AIM: Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT). METHODS: We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis. RESULTS: Forty-two patients were identified. Median age was 6.4 years (range 0.6-9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%)...
October 3, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27635231/recent-advances-in-targeted-therapy-for-ewing-sarcoma
#4
REVIEW
Kathleen I Pishas, Stephen L Lessnick
Ewing sarcoma is an aggressive, poorly differentiated neoplasm of solid bone that disproportionally afflicts the young. Despite intensive multi-modal therapy and valiant efforts, 70% of patients with relapsed and metastatic Ewing sarcoma will succumb to their disease. The persistent failure to improve overall survival for this subset of patients highlights the urgent need for rapid translation of novel therapeutic strategies. As Ewing sarcoma is associated with a paucity of mutations in readily targetable signal transduction pathways, targeting the key genetic aberration and master regulator of Ewing sarcoma, the EWS/ETS fusion, remains an important goal...
2016: F1000Research
https://www.readbyqxmd.com/read/27608846/sta-8666-a-novel-hsp90-inhibitor-sn-38-drug-conjugate-causes-complete-tumor-regression-in-preclinical-mouse-models-of-pediatric-sarcoma
#5
Christine M Heske, Arnulfo Mendoza, Leah D Edessa, Joshua T Baumgart, Sunmin Lee, Jane Trepel, David A Proia, Len Neckers, Lee J Helman
Long-term survival in patients with metastatic, relapsed, or recurrent Ewing sarcoma and rhabdomyosarcoma is dismal. Irinotecan, a topoisomerase 1 inhibitor, has activity in these sarcomas, but due to poor bioavailability of its active metabolite (SN-38) has had limited clinical efficacy. In this study we have evaluated the efficacy and toxicity of STA-8666, a novel drug conjugate which uses an HSP90 inhibitor to facilitate intracellular, tumor-targeted delivery of the topoisomerase 1 inhibitor SN-38, thus preferentially delivering and concentrating SN-38 within tumor tissue...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27589063/multiple-active-compounds-from-viscum-album-l-synergistically-converge-to-promote-apoptosis-in-ewing-sarcoma
#6
Monika Twardziok, Susann Kleinsimon, Jana Rolff, Sebastian Jäger, Angelika Eggert, Georg Seifert, Catharina I Delebinski
Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10-15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilized with cyclodextrins...
2016: PloS One
https://www.readbyqxmd.com/read/27486986/mirna-193a-5p-repression-of-p73-controls-cisplatin-chemoresistance-in-primary-bone-tumors
#7
Camille Jacques, Lidia Rodriguez Calleja, Marc Baud'huin, Thibaut Quillard, Dominique Heymann, François Lamoureux, Benjamin Ory
Osteosarcoma and Ewing Sarcoma are the two most common types of Bone Sarcomas, principally localized at the long bones of the extremities and mainly affecting adolescents and young adults. Cisplatin is one of the current options in the therapeutic arsenal of drugs available to cure these aggressive cancers. Unfortunately, chemoresistance against this agent is still a major cause of patient relapse. Thus, a better understanding of the molecular pathways by which these drugs induce cancer cell death, together with a better delineation of the origins of chemoresistance are required to improve the success rate of current treatments...
July 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27486822/bone-marrow-involvement-identifies-a-subgroup-of-advanced-ewing-sarcoma-patients-with-fatal-outcome-irrespective-of-therapy-in-contrast-to-curable-patients-with-multiple-bone-metastases-but-unaffected-marrow
#8
Uwe Thiel, Angela Wawer, Irene von Luettichau, Hans-Ulrich Bender, Franziska Blaeschke, Thomas G P Grunewald, Marc Steinborn, Barbara Röper, Halvard Bonig, Thomas Klingebiel, Peter Bader, Ewa Koscielniak, Michael Paulussen, Uta Dirksen, Heribert Juergens, Hans-Jochem Kolb, Stefan E G Burdach
PURPOSE: Advanced Ewing sarcomas have poor prognosis. They are defined by early relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols. DESIGN: Of 44 patients, 18 patients were enrolled into two subsequent MetaEICESS protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing sarcoma patients treated with EICESS 1992 between 1992 and 1996...
July 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27459981/pediatric-oncology-provider-views-on-performing-a-biopsy-of-solid-tumors-in-children-with-relapsed-or-refractory-disease-for-the-purpose-of-genomic-profiling
#9
Barrie Cohen, Michael Roth, Jonathan M Marron, Stacy W Gray, David S Geller, Bang Hoang, Richard Gorlick, Katherine A Janeway, Jonathan Gill
BACKGROUND: Patients with relapsed and refractory solid tumors have a poor prognosis. Recent advances in genomic technology have made it feasible to screen tumors for actionable mutations, with the anticipation that this may provide benefit to patients. METHODS: Pediatric oncologists were emailed an anonymous 34-question survey assessing their willingness to offer a rebiopsy to patients with relapsed disease for the purpose of tumor genomic profiling. They were presented with two scenarios evaluating morbidity and invasiveness of the procedures using the clinical examples of medulloblastoma and Ewing sarcoma...
July 26, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27423576/autonomic-dysfunction-in-multiple-sclerosis-is-better-detected-by-heart-rate-variability-and-is-not-correlated-with-central-autonomic-network-damage
#10
Gonçalo Videira, Pedro Castro, Bítia Vieira, João Pedro Filipe, Rosa Santos, Elsa Azevedo, Maria José Sá, Pedro Abreu
BACKGROUND: MS-associated autonomic dysfunction (AD) in multiple sclerosis (MS) is poorly understood and the best method for its detection unestablished. We compared classical Ewing battery and newer methods as heart rate variability (HRV) and spontaneous baroreflex sensibility (BRS) to detect AD in MS and related them to central autonomic network (CAN) lesions. METHODS: We enrolled 20 relapsing-remitting MS patients, median age of 36 (interquartile range 32-46) years, disease duration of 5...
August 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27364557/activation-of-wnt-%C3%AE-catenin-in-ewing-sarcoma-cells-antagonizes-ews-ets-function-and-promotes-phenotypic-transition-to-more-metastatic-cell-states
#11
Elisabeth A Pedersen, Rajasree Menon, Kelly M Bailey, Dafydd G Thomas, Raelene A Van Noord, Jenny Tran, Hongwei Wang, Ping Ping Qu, Antje Hoering, Eric R Fearon, Rashmi Chugh, Elizabeth R Lawlor
Ewing sarcomas are characterized by the presence of EWS/ETS fusion genes in the absence of other recurrent genetic alterations and mechanisms of tumor heterogeneity that contribute to disease progression remain unclear. Mutations in the Wnt/β-catenin pathway are rare in Ewing sarcoma but the Wnt pathway modulator LGR5 is often highly expressed, suggesting a potential role for the axis in tumor pathogenesis. We evaluated β-catenin and LGR5 expression in Ewing sarcoma cell lines and tumors and noted marked intra- and inter-tumor heterogeneity...
September 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27362300/a-phase-ii-study-of-clinical-activity-of-sch-717454-robatumumab-in-patients-with-relapsed-osteosarcoma-and-ewing-sarcoma
#12
Peter M Anderson, Stefan S Bielack, Richard G Gorlick, Keith Skubitz, Najat C Daw, Cynthia E Herzog, Odd R Monge, Alvaro Lassaletta, Erica Boldrini, Zsuzanna Pápai, Joseph Rubino, Kumudu Pathiraja, Darcy A Hille, Mark Ayers, Siu-Long Yao, Michael Nebozhyn, Brian Lu, David Mauro
BACKGROUND: Robatumumab (19D12; MK-7454 otherwise known as SCH717454) is a fully human antibody that binds to and inhibits insulin-like growth factor receptor-1 (IGF-1R). This multiinstitutional study (P04720) determined the safety and clinical efficacy of robatumumab in three separate patient groups with resectable osteosarcoma metastases (Group 1), unresectable osteosarcoma metastases (Group 2), and Ewing sarcoma metastases (Group 3). PROCEDURE: Robatumumab infusions were administered every 2 weeks and were well tolerated with minimal toxicity...
October 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27322713/insulin-like-growth-factor-receptor-inhibition-as-maintenance-therapy-for-metastatic-ewing-sarcoma
#13
Hannah Fassel, Donald Tracy, Katie Louer, Giannoula Lakka Klement
Despite the advances in oncology, the survival of children with Ewing Sarcoma metastatic at diagnosis continues to be 27% 3-year event-free survival and 34% 3-year overall survival. In other words, 7 of 10 children die within 3 years of their initial diagnosis despite intense chemotherapy, local treatment (radiation/surgery), and/or high dose busulfan-melphalan and autologous stem-cell transplantation. A chief contributor to this morbidity and mortality is the difficulty eradicating the tumor using present therapeutic modalities...
October 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27287205/identification-of-genetic-variants-in-pharmacokinetic-genes-associated-with-ewing-sarcoma-treatment-outcome
#14
S Ruiz-Pinto, G Pita, A Patiño-García, P García-Miguel, J Alonso, A Pérez-Martínez, A Sastre, G Gómez-Mariano, A Lissat, K Scotlandi, M Serra, R Ladenstein, E Lapouble, G Pierron, U Kontny, P Picci, H Kovar, O Delattre, A González-Neira
BACKGROUND: Despite the effectiveness of current treatment protocols for Ewing sarcoma (ES), many patients still experience relapse, and survival following recurrence is <15%. We aimed to identify genetic variants that predict treatment outcome in children diagnosed with ES. PATIENTS AND METHODS: We carried out a pharmacogenetic study of 384 single-nucleotide polymorphisms (SNPs) in 24 key transport or metabolism genes relevant to drugs used to treat in pediatric patients (<30 years) with histologically confirmed ES...
September 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27283964/genomic-ewsr1-fusion-sequence-as-highly-sensitive-and-dynamic-plasma-tumor-marker-in-ewing-sarcoma
#15
Manuela Krumbholz, Julia Hellberg, Benedikt Steif, Tobias Bäuerle, Clarissa Gillmann, Torsten Fritscher, Abbas Agaimy, Benjamin Frey, Joerg Juengert, Eva Wardelmann, Wolfgang Hartmann, Heribert Juergens, Uta Dirksen, Markus Metzler
PURPOSE: The application of the tumor-specific genomic fusion sequence as noninvasive biomarker for therapy monitoring in Ewing sarcoma (EwS) has been evaluated. EXPERIMENTAL DESIGN: EwS xenograft mouse models were used to explore detectability in small plasma volumes and correlation of genomic EWSR1-FLI1 copy numbers with tumor burden. Furthermore, 234 blood samples from 20 EwS patients were analyzed before and during multimodal treatment. EWSR1 fusion sequence levels in patients' plasma were quantified using droplet digital PCR and compared with tumor volumes calculated from MRI or CT imaging studies...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27245095/panobinostat-a-potential-treatment-for-metastasized-ewing-sarcoma-a-case-report
#16
Annemiek M van Maldegem, Judith V M G Bovée, Hans Gelderblom
Ewing sarcoma (ES) is a form of primary bone cancer, with few treatment options for patients who develop relapse with an overall 5-year survival of 13%. New treatment options are needed and histone deacetylase (HDAC) inhibitors show encouraging results in preclinical studies. Our patient developed inoperable progressive lung metastases and was treated with the HDAC inhibitor panobinostat. During 18 months of treatment, no new lesions appeared; the treatment was stopped due to progression. This clinical observation warrants further evaluation of HDAC inhibitors in ES...
October 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27197626/primary-ewing-sarcoma-primitive-neuroectodermal-tumor-in-the-adrenal-gland
#17
Lian Zhang, Min Yao, Masanori Hisaoka, Hironobu Sasano, Hongwen Gao
Primary Ewing sarcoma or primitive neuroectodermal tumor (PNET) of the adrenal gland is extremely rare. We report a case of Ewing sarcoma or PNET of the adrenal in a 48-year-old Chinese woman. The patient was hospitalized with left upper quadrant abdominal pain and swelling that had been present for 1 year. Computed tomography (CT) images revealed a circumscribed mass in the left adrenal region measuring 12 cm in its greatest dimension, and the mass was surgically resected. Macroscopically, the mass (13 × 10 × 8 cm(3) ) in the left adrenal gland was encapsulated, soft, appearing grayish white and yellow, and with foci of cystic degeneration, necrosis, and hemorrhage on cross-sectional...
May 20, 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27176931/can-postoperative-radiotherapy-be-omitted-in-localised-standard-risk-ewing-sarcoma-an-observational-study-of-the-euro-e-w-i-n-g-group
#18
Stéphanie Foulon, Bernadette Brennan, Nathalie Gaspar, Uta Dirksen, Lee Jeys, Anna Cassoni, Line Claude, Beatrice Seddon, Perrine Marec-Berard, Jeremy Whelan, Michael Paulussen, Arne Streitbuerger, Odile Oberlin, Heribert Juergens, Robert Grimer, Marie-Cécile Le Deley
BACKGROUND: The role of postoperative radiotherapy (PORT) in Ewing sarcoma (ES) is unclear. We assessed the impact of PORT on local control in patients with localised ES and good histological response to chemotherapy (<10% cells). PATIENTS AND METHODS: All randomised patients in the EE99-R1 trial (comparing two consolidation chemotherapy regimens) undergoing surgery after induction chemotherapy were included. Local relapse (LR) cumulative incidence was estimated using a competing risk approach...
July 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/26909278/osteoprotegerin-inhibits-bone-resorption-and-prevents-tumor-development-in-a-xenogenic-model-of-ewing-s-sarcoma-by-inhibiting-rankl
#19
Gaëlle Picarda, Etienne Matous, Jérôme Amiaud, Céline Charrier, François Lamoureux, Marie-Françoise Heymann, Franck Tirode, Bruno Pitard, Valérie Trichet, Dominique Heymann, Françoise Redini
Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development...
September 2013: Journal of Bone Oncology
https://www.readbyqxmd.com/read/26891183/conditional-survival-and-predictors-of-late-death-in-patients-with-ewing-sarcoma
#20
Jillian R Davenport, Kieuhoa T Vo, Robert Goldsby, Daniel C West, Steven G DuBois
PURPOSE: Long-term survivors of Ewing sarcoma (EWS) are at considerable risk for future complications, including late relapse and death. Data on prognostic factors for late death in those who have survived beyond 5 years are lacking. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. We obtained clinical features and outcome data on 1,351 patients with EWS who had survived 60 months or more. From these data, we performed univariate and multivariable analyses of overall survival (OS) using log-rank tests and Cox proportional hazard models...
June 2016: Pediatric Blood & Cancer
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