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medulloblastoma children

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https://www.readbyqxmd.com/read/29778738/risk-adapted-therapy-for-young-children-with-medulloblastoma-sjyc07-therapeutic-and-molecular-outcomes-from-a-multicentre-phase-2-trial
#1
Giles W Robinson, Vasilisa A Rudneva, Ivo Buchhalter, Catherine A Billups, Sebastian M Waszak, Kyle S Smith, Daniel C Bowers, Anne Bendel, Paul G Fisher, Sonia Partap, John R Crawford, Tim Hassall, Daniel J Indelicato, Frederick Boop, Paul Klimo, Noah D Sabin, Zoltan Patay, Thomas E Merchant, Clinton F Stewart, Brent A Orr, Jan O Korbel, David T W Jones, Tanvi Sharma, Peter Lichter, Marcel Kool, Andrey Korshunov, Stefan M Pfister, Richard J Gilbertson, Robert P Sanders, Arzu Onar-Thomas, David W Ellison, Amar Gajjar, Paul A Northcott
BACKGROUND: Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure...
May 16, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29776650/signaling-pathway-deregulation-and-molecular-alterations-across-pediatric-medulloblastomas
#2
REVIEW
B Lhermitte, A F Blandin, A Coca, E Guerin, A Durand, N Entz-Werlé
Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs)...
May 15, 2018: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29771176/potential-use-of-cxcl12-cxcr4-and-sonic-hedgehog-pathways-as-therapeutic-targets-in-medulloblastoma
#3
Marla Karine Amarante, Glauco Akelinghton Freire Vitiello, Marcos Henrique Rosa, Igor Alves Mancilla, Maria Angelica Ehara Watanabe
Medulloblastoma (MB) is the most common malignant brain tumor occurring in children, and although high long-term survival rates have been reached with current therapeutic protocols, several neurological injuries are still observed among survivors. It has been shown that the development of MB is highly dependent on the microenvironment surrounding it and that the CXCL12 chemokine and its receptor, CXCR4 and the Sonic Hedgehog (SHH) pathway are crucial for cerebellar development, coordinating proliferation and migration of embryonic cells and malfunctions in these axes can lead to MB development...
May 17, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29753700/spectrum-and-prevalence-of-genetic-predisposition-in-medulloblastoma-a-retrospective-genetic-study-and-prospective-validation-in-a-clinical-trial-cohort
#4
Sebastian M Waszak, Paul A Northcott, Ivo Buchhalter, Giles W Robinson, Christian Sutter, Susanne Groebner, Kerstin B Grund, Laurence Brugières, David T W Jones, Kristian W Pajtler, A Sorana Morrissy, Marcel Kool, Dominik Sturm, Lukas Chavez, Aurelie Ernst, Sebastian Brabetz, Michael Hain, Thomas Zichner, Maia Segura-Wang, Joachim Weischenfeldt, Tobias Rausch, Balca R Mardin, Xin Zhou, Cristina Baciu, Christian Lawerenz, Jennifer A Chan, Pascale Varlet, Lea Guerrini-Rousseau, Daniel W Fults, Wiesława Grajkowska, Peter Hauser, Nada Jabado, Young-Shin Ra, Karel Zitterbart, Suyash S Shringarpure, Francisco M De La Vega, Carlos D Bustamante, Ho-Keung Ng, Arie Perry, Tobey J MacDonald, Pablo Hernáiz Driever, Anne E Bendel, Daniel C Bowers, Geoffrey McCowage, Murali M Chintagumpala, Richard Cohn, Timothy Hassall, Gudrun Fleischhack, Tone Eggen, Finn Wesenberg, Maria Feychting, Birgitta Lannering, Joachim Schüz, Christoffer Johansen, Tina V Andersen, Martin Röösli, Claudia E Kuehni, Michael Grotzer, Kristina Kjaerheim, Camelia M Monoranu, Tenley C Archer, Elizabeth Duke, Scott L Pomeroy, Redmond Shelagh, Stephan Frank, David Sumerauer, Wolfram Scheurlen, Marina V Ryzhova, Till Milde, Christian P Kratz, David Samuel, Jinghui Zhang, David A Solomon, Marco Marra, Roland Eils, Claus R Bartram, Katja von Hoff, Stefan Rutkowski, Vijay Ramaswamy, Richard J Gilbertson, Andrey Korshunov, Michael D Taylor, Peter Lichter, David Malkin, Amar Gajjar, Jan O Korbel, Stefan M Pfister
BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED)...
May 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29742885/malignant-brain-tumours-in-children-present-and-future-perspectives
#5
REVIEW
James T Rutka
In contrast to many of the malignant tumors that occur in the central nervous system in adults, the management, responses to therapy, and future perspectives of children with malignant lesions of the brain hold considerable promise. Within the past 5 years, remarkable progress has been made with our understanding of the basic biology of the molecular genetics of several pediatric malignant brain tumors including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumour, and high grade glioma/diffuse intrinsic pontine glioma...
May 2018: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/29742881/medulloblastoma-in-the-molecular-era
#6
REVIEW
Claudia Miranda Kuzan-Fischer, Kyle Juraschka, Michael D Taylor
Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms...
May 2018: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/29730815/pd-1-pd-l1-and-immune-related-gene-expression-pattern-in-pediatric-malignant-brain-tumors-clinical-correlation-with-survival-data-in-korean-population
#7
Kihwan Hwang, Eun Jung Koh, Eun Jin Choi, Tae Hee Kang, Jung Ho Han, Gheeyoung Choe, Sung-Hye Park, Jennifer Holmes Yearley, Lakshmanan Annamalai, Wendy Blumenschein, Manjiri Sathe, Terri McClanahan, Hun Jung, Kyu-Chang Wang, Seung-Ki Kim, Chae-Yong Kim
BACKGROUND: PD-L1 expression has been evaluated as a predictive biomarker for immunotherapy in numerous tumor types. However, very limited data are available in pediatric brain tumors. The aim of this study was to characterize PD-1 and PD-L1 expressions of four pediatric malignant brain tumors and gene expression profile. METHODS: This study included 89 pediatric patients receiving standard treatment at Seoul National University Children's Hospital and Seoul National University Bundang Hospital between 1990 and 2014: atypical teratoid/rhabdoid tumor (AT/RT) 20; ependymoma (EPN) 20; high grade glioma (HGG) 21; and medulloblastoma (MBL) 28...
May 5, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29716738/neuropsychological-consequences-of-childhood-medulloblastoma-and-possible-interventions-a-review
#8
E Doger de Spéville, V Kieffer, C Dufour, J Grill, M Noulhiane, L Hertz-Pannier, M Chevignard
BACKGROUND: Children who have been treated for a medulloblastoma often suffer long-term cognitive impairments that often negatively affect their academic performance and quality of life. In this article, we will review the neuropsychological consequences of childhood medulloblastoma and discuss the risk factors known to influence the presence and severity of these cognitive impairments and possible interventions to improve their quality of life. METHODS: This narrative review was based on electronic searches of PubMed to identify all relevant studies...
April 28, 2018: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29712574/durable-regression-of-medulloblastoma-after-regional-and-intravenous-delivery-of-anti-her2-chimeric-antigen-receptor-t-cells
#9
Anandani Nellan, Christopher Rota, Robbie Majzner, Cynthia M Lester-McCully, Andrea M Griesinger, Jean M Mulcahy Levy, Nicholas K Foreman, Katherine E Warren, Daniel W Lee
BACKGROUND: Standard-of-care therapies for treating pediatric medulloblastoma have long-term side effects, even in children who are cured. One emerging modality of cancer therapy that could be equally effective without such side effects would be chimeric antigen receptor (CAR) T cells. Knowing that human epidermal growth factor receptor 2 (HER2) is overexpressed in many medulloblastomas and has been used as a CAR T target before, we sought to evaluate the efficacy of more sophisticated anti-HER2 CAR T cells, as well as the feasibility and efficacy of different routes of delivering these cells, for the treatment of pediatric medulloblastoma...
April 30, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29706825/medulloblastoma-in-a-toddler-with-gorlin-syndrome
#10
Mohamad G Al-Rahawan, Sorleen Trevino, Roy Jacob, Jeffrey C Murray, Mohamad M Al-Rahawan
Gorlin syndrome (GS) is a rare hereditary multisystem disorder caused by mutations in PTCH1, PTCH2 , or SUFU . It is characterized by multiple anomalies and an increased risk of developing various tumors. Basal cell carcinoma is most common, and medulloblastoma (MB) is especially frequent in patients with SUFU mutations. MB treatment often includes radiation therapy in patients older than 3 years; however, such treatment is very toxic to patients with GS. Most reported cases of MB in patients with GS present after GS is diagnosed...
April 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29693784/meta-analysis-of-the-incidence-and-patterns-of-second-neoplasms-after-photon-craniospinal-irradiation-in-children-with-medulloblastoma
#11
Abhishek Bavle, Sayani Tewari, Amy Sisson, Murali Chintagumpala, Michael Anderson, Arnold C Paulino
BACKGROUND: Second neoplasms (SNs) are a well-established long-term adverse effect of radiation therapy (RT), but there are limited data regarding their incidence and location relative to the radiation field, specific to medulloblastoma (MB) survivors after craniospinal irradiation (CSI). METHODS: A systematic literature review, per Preferred Reporting Items for Systematic Reviews and Meta-Analyses, identified six studies reporting the incidence and locations of SNs for 1,114 patients with MB, after CSI, with a median follow-up of ∼9 years (7...
April 25, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29692919/case-based-review-pediatric-medulloblastoma
#12
REVIEW
Cassie N Kline, Roger J Packer, Eugene I Hwang, David R Raleigh, Steve Braunstein, Corey Raffel, Pratiti Bandopadhayay, David A Solomon, Mariam Aboian, Soonmee Cha, Sabine Mueller
Medulloblastoma is the most common malignant brain tumor affecting children. These tumors are high grade with propensity to metastasize within the central nervous system and, less frequently, outside the neuraxis. Recent advancements in molecular subgrouping of medulloblastoma refine diagnosis and improve counseling in regards to overall prognosis. Both are predicated on the molecular drivers of each subgroup-WNT-activated, SHH-activated, group 3, and group 4. The traditional therapeutic mainstay for medulloblastoma includes a multimodal approach with surgery, radiation, and multiagent chemotherapy...
September 2017: Neuro-oncology Practice
https://www.readbyqxmd.com/read/29675068/cerebellar-mutism-syndrome-following-midline-posterior-fossa-tumor-resection-in-children-an-institutional-experience
#13
Nand Kishore Gora, Ashok Gupta, Virendra Deo Sinha
Aim: Cerebellar mutism (CM) syndrome is a well-known and annoying complication of posterior fossa surgery in the pediatric age group. Risk factors such as the type of tumor, size, involvement of posterior fossa structures and hydrocephalus, and postoperative cerebellar swelling for CM were investigated in this study. Materials and Methods: A consecutive series of 33 children with midline posterior fossa tumors were operated at the SMS Medical College and Hospital, Department of Neurosurgery, Jaipur India, between September 2015 and December 2016...
October 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/29651356/cerebellar-medulloblastoma-in-middle-to-late-adulthood
#14
Majid Aljoghaiman, Mahmoud S Taha, Marwah M Abdulkader
Medulloblastoma is a malignant brain tumor that is typically seen in children. It is classified as an embryonal tumor, classically located within the posterior fossa. When it involves the fourth ventricle, the patient commonly presents with signs and symptoms of raised intracranial pressure secondary to obstructive hydrocephalus. It is exceedingly rare for Medulloblastoma to occur in middle and late adulthood. In this paper, we present a case of a 51-year-old man who presented with a posterior fossa mass that was diagnosed later as Medulloblastoma...
2018: Case Reports in Pathology
https://www.readbyqxmd.com/read/29644158/bilateral-simultaneous-temporal-relapses-of-medulloblastoma
#15
Mauricio Martinez-Moreno, Olga O Galván de la Cruz, Christian H Flores-Balcázar, Samuel Rosales-Pérez, Daniel Rembao-Bojórquez, Sergio Moreno-Jiménez
Supratentorial relapses are a common component of medulloblastoma after failure of treatment. Craniospinal irradiation (CSI) to cerebrospinal fluid-bearing areas is an essential part of the management of these tumors both in adults and children. Failure of treatment in specific anatomical regions can be attributable to technical inaccuracies in CSI technique leading to radiation underdosing in such areas. We present two cases of patients with bilateral simultaneous metastasis of a primary medulloblastoma treated, in both cases, four years before the recurrence...
February 8, 2018: Curēus
https://www.readbyqxmd.com/read/29624145/surgical-decision-making-in-the-management-of-childhood-tumors-of-the-cns-disseminated-at-presentation
#16
Matthew A Kirkman, Richard Hayward, Kim Phipps, Kristian Aquilina
OBJECTIVE It is relatively unusual for pediatric CNS tumors to be disseminated at presentation, and the literature on the clinical features, management, and outcomes of this specific group is scarce. Surgical management in this population is often challenging, particularly in the presence of hydrocephalus. The authors present their recent experience of treating pediatric CNS tumors that were disseminated at presentation, and they compare these lesions with focal tumors. METHODS The authors performed a retrospective review of prospectively collected data on children presenting to a tertiary center between 2003 and 2016 inclusive...
April 6, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29616106/data-mining-of-pediatric-medulloblastoma-microarray-expression-reveals-a-novel-potential-subdivision-of-the-group-4-molecular-subgroup
#17
Rosa Angélica Castillo-Rodríguez, Víctor Manuel Dávila-Borja, Sergio Juárez-Méndez
Medulloblastoma is the most common type of solid brain tumor in children. This type of embryonic tumor is highly heterogeneous and has been classified into 4 molecular subgroups based on their gene expression profiles: WNT, SHH, Group 3 (G3) and Group 4 (G4). WNT and SHH tumors exhibit the specific dysregulation of genes and pathways, whereas G3 and G4 tumors, two of the more frequent subtypes, are the least characterized. Thus, novel markers to aid in the diagnosis, prognosis and management of medulloblastoma are required...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29582169/medulloblastoma-wnt-activated-shh-activated-clinical-impact-of-molecular-analysis-and-histogenetic-evaluation
#18
REVIEW
Eduardo Cambruzzi
PURPOSE: Medulloblastoma (MDB) is a small cell poorly differentiated embryonal tumor of the cerebellum, which more frequently compromises children. Overall prognosis is favorable, but dependent of stage, histopathological pattern and molecular group. Approximately 30% of the affected patients will die from the disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS) has been classified MDB into four principal groups: WNT-activated MDB, SHH-activated MDB, group 3 MDB, and group 4 MDB...
March 26, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29574250/a-pre-clinical-assessment-of-the-pan-erbb-inhibitor-dacomitinib-in-pediatric-and-adult-brain-tumors
#19
Raelene Endersby, Jacqueline Whitehouse, Hilary Hii, Sameer A Greenall, Terrance G Johns, Nicholas G Gottardo
Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with significant long-term debilitating side effects. The prognosis for pineoblastoma is age-dependent, with little chance of a cure for children younger than three years. More effective molecularly targeted strategies are urgently required to treat these cancers...
March 22, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29511348/combined-bet-bromodomain-and-cdk2-inhibition-in-myc-driven-medulloblastoma
#20
Sara Bolin, Anna Borgenvik, Camilla U Persson, Anders Sundström, Jun Qi, James E Bradner, William A Weiss, Yoon-Jae Cho, Holger Weishaupt, Fredrik J Swartling
Medulloblastoma (MB) is the most common malignant brain tumor in children. MYC genes are frequently amplified and correlate with poor prognosis in MB. BET bromodomains recognize acetylated lysine residues and often promote and maintain MYC transcription. Certain cyclin-dependent kinases (CDKs) are further known to support MYC stabilization in tumor cells. In this report, MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively...
March 7, 2018: Oncogene
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