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https://www.readbyqxmd.com/read/28325818/paper-of-note-in-science-translational-medicine9-381
#1
Leslie K Ferrarelli
This week's article describes a therapy that may enable macrophages to recognize and kill tumor cells in pediatric patients with brain cancer.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325133/outcome-for-children-treated-for-medulloblastoma-and-supratentorial-primitive-neuroectodermal-tumor-cns-pnet-a-retrospective-analysis-spanning-40-years-of-treatment
#2
Einar Stensvold, Bård Kronen Krossnes, Tryggve Lundar, Bernt J Due-Tønnessen, Radek Frič, Paulina Due-Tønnessen, Anne Grete Bechensteen, Tor Åge Myklebust, Tom Børge Johannesen, Petter Brandal
BACKGROUND: Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET) are among the most common pediatric brain tumors. The diagnosis, treatment, and outcome of MB/CNS-PNET patients treated during the last four decades at Oslo University Hospital (OUH) are described. MATERIAL AND METHODS: All patients younger than 20 years of age diagnosed and treated for MB/CNS-PNET at OUH between 1 January 1974 and 31 December 2013 were identified...
March 21, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#3
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28302901/treatment-of-renal-angiomyolipoma-and-other-hamartomas-in-patients-with-tuberous-sclerosis-complex
#4
REVIEW
Joshua A Samuels
Tuberous sclerosis complex is an autosomal dominant genetic disease characterized by growth of benign tumors (hamartomas) in multiple organs, especially the kidneys, brain, heart, lungs, and skin. Tuberous sclerosis complex is usually caused by a mutation in either the tuberous sclerosis complex 1 or tuberous sclerosis complex 2 gene, resulting in constitutive activation of mammalian target of rapamycin signaling. Currently, mammalian target of rapamycin inhibitors are recommended in adult patients with tuberous sclerosis complex for the treatment of asymptomatic, growing renal angiomyolipoma that are >3 cm in diameter and pediatric or adult patients with brain lesions (subependymal giant cell astrocytoma) that either are growing or are not amenable to surgical resection...
March 16, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#5
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28300707/psychiatric-and-psychological-impact-of-surgery-while-awake-in-children-for-resection-of-brain-tumors
#6
Elise Riquin, Mickael Dinomais, Jean Malka, Thierry Lehousse, Philippe Duverger, Philippe Menei, Matthieu Delion
Intraoperative direct stimulation during surgery while awake is considered to be the gold standard for identifying eloquent cortical sites. Only a few studies have referenced the psychological impact of this event in the pediatric population. OBJECTIVE: The aim of this clinical study is to present the psychological aspects of surgery while awake in children. We question the psychiatric contraindications and age limits, and the impact on children, with particular attention to the psychological conditioning and experience of these patients...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28298418/disrupting-the-cd47-sirp%C3%AE-anti-phagocytic-axis-by-a-humanized-anti-cd47-antibody-is-an-efficacious-treatment-for-malignant-pediatric-brain-tumors
#7
Sharareh Gholamin, Siddhartha S Mitra, Abdullah H Feroze, Jie Liu, Suzana A Kahn, Michael Zhang, Rogelio Esparza, Chase Richard, Vijay Ramaswamy, Marc Remke, Anne K Volkmer, Stephen Willingham, Anitha Ponnuswami, Aaron McCarty, Patricia Lovelace, Theresa A Storm, Simone Schubert, Gregor Hutter, Cyndhavi Narayanan, Pauline Chu, Eric H Raabe, Griffith Harsh, Michael D Taylor, Michelle Monje, Yoon-Jae Cho, Ravi Majeti, Jens P Volkmer, Paul G Fisher, Gerald Grant, Gary K Steinberg, Hannes Vogel, Michael Edwards, Irving L Weissman, Samuel H Cheshier
Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28296130/determinants-of-quality-of-life-outcomes-for-survivors-of-pediatric-brain-tumors
#8
Maru Barrera, Eshetu G Atenafu, Fiona Schulte, Ute Bartels, Lillian Sung, Laura Janzen, Joanna Chung, Danielle Cataudella, Kelly Hancock, Amani Saleh, Douglas Strother, Dina McConnell, Andrea Downie, Juliette Hukin, Shayna Zelcer
INTRODUCTION: To describe the quality of life (QOL) of pediatric brain tumor survivors (PBTSs) prospectively and to identify potential medical, personal and family contextual factors associated with QOL. METHODS: Ninety-one PBTSs (8-16 years) who were off treatment and attending a regular classroom participated. Self- and caregiver-proxy-reported on QOL at baseline, 2 and 8 months. At baseline, cognitive, executive function, attention and memory, medical and demographics information were attained...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28293736/5ala-in-pediatric-brain-tumors-is-not-routinely-beneficial
#9
Jonathan Roth, Shlomi Constantini
PURPOSE: Over recent years, 5-aminoluvolinic acid (5ALA) has been increasingly used for resection guidance in adult high-grade gliomas. However, amongst pediatric patients, publication of intraoperative fluorescence has been limited, with inconsistent outcomes. We describe our experience and intraoperative finding amongst children with various brain tumors that were given 5ALA prior to tumor resection. METHODS: Since October 2014, data regarding intraoperative findings amongst children that received 5ALA prior to tumor resection were prospectively collected...
March 14, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28292958/molecular-mechanisms-and-therapeutic-targets-in-pediatric-brain-tumors
#10
REVIEW
Kun-Wei Liu, Kristian W Pajtler, Barbara C Worst, Stefan M Pfister, Robert J Wechsler-Reya
Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28291428/the-durability-of-endoscopic-third-ventriculostomy-and-ventriculoperitoneal-shunts-in-children-with-hydrocephalus-following-posterior-fossa-tumor-resection-a-systematic-review-and-time-to-failure-analysis
#11
Michael C Dewan, Jaims Lim, Chevis N Shannon, John C Wellons
OBJECTIVE Up to one-third of patients with a posterior fossa brain tumor (PFBT) will experience persistent hydrocephalus mandating permanent CSF diversion. The optimal hydrocephalus treatment modality is unknown; the authors sought to compare the durability between endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) therapy in the pediatric population. METHODS The authors conducted a systematic review of articles indexed in PubMed between 1986 and 2016 describing ETV and/or VPS treatment success/failure and time-to-failure rate in patients < 19 years of age with hydrocephalus related to a PFBT...
March 10, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28291423/preclinical-evaluation-of-convection-enhanced-delivery-of-liposomal-doxorubicin-to-treat-pediatric-diffuse-intrinsic-pontine-glioma-and-thalamic-high-grade-glioma
#12
A Charlotte P Sewing, Tonny Lagerweij, Dannis G van Vuurden, Michaël H Meel, Susanna J E Veringa, Angel M Carcaboso, Pieter J Gaillard, W Peter Vandertop, Pieter Wesseling, David Noske, Gertjan J L Kaspers, Esther Hulleman
OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models...
February 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28291373/neoadjuvant-chemotherapy-for-atypical-teratoid-rhabdoid-tumors-case-report
#13
Meena Thatikunta, Ian Mutchnick, Jennifer Elster, Matthew P Thompson, Michael A Huang, Aaron C Spalding, Thomas Moriarty
Atypical teratoid rhabdoid tumors (ATRTs) are a rare pediatric brain tumor with high mortality rate. Several large series have reported achieving gross-total resection (GTR) in less than 50% of patients due to the lesions' large size, vascularity, and limited blood volume in young patients. While neoadjuvant chemotherapy for choroid plexus carcinomas in pediatric patients has become widely accepted, it has not been used as widely for other pediatric brain tumors. To the best of the authors' knowledge, there are only 3 published cases of neoadjuvant chemotherapy for ATRTs...
March 10, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28290001/choroid-plexus-tumors-in-adult-and-pediatric-populations-the-cleveland-clinic-and-university-hospitals-experience
#14
Michal Bahar, Hasan Hashem, Tanya Tekautz, Sarah Worley, Anne Tang, Peter de Blank, Johannes Wolff
Choroid plexus tumors (CPT) are rare neoplasms accounting for 1-4% of all pediatric brain tumors. They are divided into choroid plexus papilloma (CPP), atypical choroid plexus papilloma (APP) and choroid plexus carcinoma (CPC). CPTs are known to primarily affect children less than 2 years of age. Gross total resection is the most important predictor of survival especially in CPC. Although small case series have been published, limited clinical data are available to describe treatment and outcome of CPTs. More clinical data would be necessary to complete the picture, particularly in populations that are not age limited...
March 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28285334/incidence-of-cns-tumors-in-appalachian-children
#15
Bin Huang, Alice Luo, Eric B Durbin, Ellen Lycan, Thomas Tucker, Quan Chen, Craig Horbinski, John L Villano
Determine whether the risk of astrocytomas in Appalachian children is higher than the national average. We compared the incidence of pediatric brain tumors in Appalachia versus non-Appalachia regions, covering years 2000-2011. The North American Association of Central Cancer Registries (NAACCR) collects population-based data from 55 cancer registries throughout U.S. and Canada. All invasive primary (i.e. non-metastatic tumors), with age at diagnosis 0-19 years old, were included. Nearly 27,000 and 2200 central nervous system (CNS) tumors from non-Appalachia and Appalachia, respectively comprise the cohorts...
March 11, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28276480/selective-targeting-of-hdac1-2-elicits-anticancer-effects-through-gli1-acetylation-in-preclinical-models-of-shh-medulloblastoma
#16
Sonia Coni, Anna Barbara Mancuso, Laura Di Magno, Giulia Sdruscia, Simona Manni, Silvia Maria Serrao, Dante Rotili, Eleonora Spiombi, Francesca Bufalieri, Marialaura Petroni, Monika Kusio-Kobialka, Enrico De Smaele, Elisabetta Ferretti, Carlo Capalbo, Antonello Mai, Pawel Niewiadomski, Isabella Screpanti, Lucia Di Marcotullio, Gianluca Canettieri
SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263309/ezh2-is-a-potential-therapeutic-target-for-h3k27m-mutant-pediatric-gliomas
#17
Faizaan Mohammad, Simon Weissmann, Benjamin Leblanc, Deo P Pandey, Jonas W Højfeldt, Itys Comet, Chunqin Zheng, Jens Vilstrup Johansen, Nicolas Rapin, Bo T Porse, Andrey Tvardovskiy, Ole N Jensen, Nagore G Olaciregui, Cinzia Lavarino, Mariona Suñol, Carmen de Torres, Jaume Mora, Angel M Carcaboso, Kristian Helin
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that is located in the pons and primarily affects children. Nearly 80% of DIPGs harbor mutations in histone H3 genes, wherein lysine 27 is substituted with methionine (H3K27M). H3K27M has been shown to inhibit polycomb repressive complex 2 (PRC2), a multiprotein complex responsible for the methylation of H3 at lysine 27 (H3K27me), by binding to its catalytic subunit EZH2. Although DIPGs with the H3K27M mutation show global loss of H3K27me3, several genes retain H3K27me3...
February 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28260349/somatic-structural-variations-in-pediatric-brain-tumors-an-update
#18
Zhengwei Li, Qingzeng Sun, Yingchun Shi
Pediatrics brain tumours are the second most frequent malignancy in children, and the most common cause of cancer-related deaths in both the 0-14-year and the 15-24-year age group. Although, pediatrics high-grade glioma (pHGG) is a histologically similar tumour to that arising in adults, these are distinct biological diseases, differing in copy number profiles and driver genetic alterations. Recent sequencing initiatives have conclusively shown the existence of subgroups of HGG marked by distinct driver mutations, which are significantly enriched in young children (H3F3A K27M), teenagers and young adults (H3F3A G34R/V), and middle- aged adults (IDH1/2)...
March 3, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28257280/applying-the-international-classification-of-functioning-children-and-youth-version-to-pediatric-neuro-oncology
#19
Thomas Pletschko, Anna Felnhofer, Agathe Schwarzinger, Liesa Weiler, Irene Slavc, Ulrike Leiss
Given the increased survival rates in patients with pediatric central nervous system tumors, late effects such as treatment- and/or illness-related neurologic sequelae as well as neuropsychological deficits and social difficulties have moved into focus in follow-up care. In order to provide personalized treatment recommendations for pediatric brain tumor survivors, it is crucial not only to assess cognitive impairments but also to measure a patient's functional deficiencies, for example, restricted participation in everyday social activities...
January 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28253733/rationale-and-design-of-a-phase-i-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#20
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy; and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor specific tropism and potential efficacy in the treatment of malignant brain tumors...
February 24, 2017: Human Gene Therapy. Clinical Development
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