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Pediatric brain cancer

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https://www.readbyqxmd.com/read/28333115/modeling-and-targeting-myc-genes-in-childhood-brain-tumors
#1
REVIEW
Sonja Hutter, Sara Bolin, Holger Weishaupt, Fredrik J Swartling
Brain tumors are the second most common group of childhood cancers, accounting for about 20%-25% of all pediatric tumors. Deregulated expression of the MYC family of transcription factors, particularly c-MYC and MYCN genes, has been found in many of these neoplasms, and their expression levels are often correlated with poor prognosis. Elevated c-MYC/MYCN initiates and drives tumorigenesis in many in vivo model systems of pediatric brain tumors. Therefore, inhibition of their oncogenic function is an attractive therapeutic target...
March 23, 2017: Genes
https://www.readbyqxmd.com/read/28325818/paper-of-note-in-science-translational-medicine9-381
#2
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/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/28292958/molecular-mechanisms-and-therapeutic-targets-in-pediatric-brain-tumors
#4
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/28285334/incidence-of-cns-tumors-in-appalachian-children
#5
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/28260349/somatic-structural-variations-in-pediatric-brain-tumors-an-update
#6
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/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
#7
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
https://www.readbyqxmd.com/read/28248691/prospective-evaluation-of-postural-control-and-gait-in-pediatric-patients-with-cancer-after-a-4-week-inpatient-rehabilitation-program
#8
Carsten Müller, Dieter Rosenbaum, Konstantin A Krauth
OBJECTIVE: The aim of the study was to investigate the effects of a 4-wk inpatient rehabilitation program on postural control and gait in pediatric patients with cancer. DESIGN: Eighty-eight patients with brain tumors (n = 59) and bone/soft tissue sarcomas (n = 29) were evaluated. Postural control was assessed examining the velocity of the center of pressure and single-leg stance time on a pressure distribution platform. Walk ratio, a measure of neuromotor control, was used to evaluate intervention effects on gait...
February 28, 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28248256/integrated-proteomic-and-transcriptomic-based-approaches-to-identifying-signature-biomarkers-and-pathways-for-elucidation-of-daoy-and-uw228-subtypes
#9
Roger Higdon, Jessie Kala, Devan Wilkins, Julia Fangfei Yan, Manveen K Sethi, Liang Lin, Siqi Liu, Elizabeth Montague, Imre Janko, John Choiniere, Natali Kolker, William S Hancock, Eugene Kolker, Susan Fanayan
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Patient survival has remained largely the same for the past 20 years, with therapies causing significant health, cognitive, behavioral and developmental complications for those who survive the tumor. In this study, we profiled the total transcriptome and proteome of two established MB cell lines, Daoy and UW228, using high-throughput RNA sequencing (RNA-Seq) and label-free nano-LC-MS/MS-based quantitative proteomics, coupled with advanced pathway analysis...
February 3, 2017: Proteomes
https://www.readbyqxmd.com/read/28245795/in-search-of-druggable-targets-for-gbm-amino-acid-metabolism
#10
Eduard H Panosyan, Henry J Lin, Jan Koster, Joseph L Lasky
BACKGROUND: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database ( http://r2.amc.nl ) analyses were carried out to screen for such targets among 95 AA related enzymes. METHODS: First, we identified the genes that were differentially expressed in GBMs (3 datasets) compared to non-GBM brain tissues (5 datasets), or were associated with survival differences. Further, protein expression for these enzymes was also analyzed in high grade gliomas (HGGs) (proteinatlas...
February 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28218785/inhibition-of-shh-pathway-mechanisms-by-arsenic-trioxide-in-pediatric-medulloblastomas-a-comprehensive-literature-review
#11
REVIEW
P H S Klinger, A F Andrade, L E A Delsin, R G P Queiroz, C A Scrideli, L G Tone, E T Valera
Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28214639/congenital-glioblastoma-with-distinct-clinical-and-molecular-characteristics-case-reports-and-a-literature-review
#12
Masahiro Kameda, Yoshihiro Otani, Tomotsugu Ichikawa, Akira Shimada, Koichi Ichimura, Isao Date
BACKGROUND: The molecular diagnosis of brain tumors is important in classifying tumors and determining appropriate treatment. Congenital glioblastoma multiforme (GBM) is a rare tumor that occurs in infants, and the prognosis is poor. Approximately 60 patients diagnosed as congenital GBM have been reported. However, few reports have conducted molecular analyses of congenital GBM. CASE DESCRIPTION: We describe two congenital GBM patients treated in our hospital, and report results of immunohistochemistry, fluorescent in situ hybridization (FISH), direct sequencing, and methylation analyses...
February 15, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#13
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
March 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28186969/high-oct4a-levels-drive-tumorigenicity-and-metastatic-potential-of-medulloblastoma-cells
#14
Patrícia Benites Gonçalves da Silva, Márcia Cristina Teixeira Dos Santos, Carolina Oliveira Rodini, Carolini Kaid, Márcia Cristina Leite Pereira, Gabriela Furukawa, Daniel Sanzio Gimenes da Cruz, Mauricio Barbugiani Goldfeder, Clarissa Ribeiro Reily Rocha, Carla Rosenberg, Oswaldo Keith Okamoto
Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#15
Andres Morales La Madrid, Mark W Kieran
Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28174375/-characteristics-of-adolescent-and-young-adult-cancer
#16
Keizo Horibe
In adolescent and young adult(AYA)population, cancer is the leading cause of death due to illness with the lowest mortality rate as well as children, and national measures for cancer was left behind. Leukemia, lymphomas, brain tumors, thyroid cancer, ovarian cancer, cervical cancer, breast cancer, testicular cancer and bone and soft tissue sarcomas account for majority of the cancers in this age group. There has been no significant improvement in AYA patients in contrast to other age groups. AYA patients with cancer are under growing independency, starting in life to the community, and reproductive age...
January 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28156496/influence-of-early-phase-clinical-trial-enrollment-on-patterns-of-end-of-life-care-for-children-with-advanced-cancer
#17
Chalinee Monsereenusorn, Clement Ma, Hasan Al-Sayegh, Joanne Wolfe, Carlos Rodriguez-Galindo
151 Background: Early phase clinical trials are critical to enhancing therapies for children with advanced cancer. However, trial enrollment may intensify end-of-life (EOL) care. We evaluated patterns of EOL care for patients at a large cancer center. METHODS: Single-center, retrospective cohort study of pediatric oncology patients, ages 6 months-21 years, who died in 2010-2014. We queried electronic medical records to assess frequencies of medical procedures (e.g. intubations), clinic visits, and hospital admissions in the last 6 months of life...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28148893/stem-cell-cultures-derived-from-pediatric-brain-tumors-accurately-model-the-originating-tumors
#18
Anna Wenger, Susanna Larsson, Anna Danielsson, Kirstine Juul Elbæk, Petronella Kettunen, Magnus Tisell, Magnus Sabel, Birgitta Lannering, Claes Nordborg, Elizabeth Schepke, Helena Carén
Brain tumors are the leading cause of cancer-related death in children but high-grade gliomas in children and adolescents have remained a relatively under-investigated disease despite this. A better understanding of the cellular and molecular pathogenesis of the diseases is required in order to improve the outcome for these children. In vitro-cultured primary tumor cells from patients are indispensable tools for this purpose by enabling functional analyses and development of new therapies. However, relevant well-characterized in vitro cultures from pediatric gliomas cultured under serum-free conditions have been lacking...
January 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115362/mouse-models-of-pediatric-supratentorial-high-grade-glioma-reveal-how-cell-of-origin-influences-tumor-development-and-phenotype
#19
Smitha Sreedharan, Naga Prathyusha Maturi, Yuan Xie, Anders Sundström, Malin Jarvius, Sylwia Libard, Irina Alafuzoff, Holger Weishaupt, Mårten Fryknäs, Rolf Larsson, Fredrik J Swartling, Lene Uhrbom
High-grade glioma (HGG) is a group of primary malignant brain tumors with dismal prognosis. Whereas adult HGG has been studied extensively, childhood HGG, a relatively rare disease, is less well-characterized. Here, we present two novel platelet-derived growth factor (PDGF)-driven mouse models of pediatric supratentorial HGG. Tumors developed from two different cells of origin reminiscent of neural stem cells (NSC) or oligodendrocyte precursor cells (OPC). Cross-species transcriptomics showed that both models are closely related to human pediatric HGG as compared with adult HGG...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28104717/clinical-targeted-exome-based-sequencing-in-combination-with-genome-wide-copy-number-profiling-precision-medicine-analysis-of-203-pediatric-brain-tumors
#20
Shakti H Ramkissoon, Pratiti Bandopadhayay, Jaeho Hwang, Lori A Ramkissoon, Noah F Greenwald, Steven E Schumacher, Ryan O'Rourke, Nathan Pinches, Patricia Ho, Hayley Malkin, Claire Sinai, Mariella Filbin, Ashley Plant, Wenya Linda Bi, Michael S Chang, Edward Yang, Karen D Wright, Peter E Manley, Matthew Ducar, Sanda Alexandrescu, Hart Lidov, Ivana Delalle, Liliana C Goumnerova, Alanna J Church, Katherine A Janeway, Marian H Harris, Laura E MacConaill, Rebecca D Folkerth, Neal I Lindeman, Charles D Stiles, Mark W Kieran, Azra H Ligon, Sandro Santagata, Adrian M Dubuc, Susan N Chi, Rameen Beroukhim, Keith L Ligon
BACKGROUND: Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice are not yet well established. METHODS: Profile is an institution-wide prospective clinical research initiative that uses targeted sequencing to identify targetable alterations in tumors. OncoPanel, a multiplexed targeted exome-sequencing platform that includes 300 cancer-causing genes, was used to assess single nucleotide variants and rearrangements/indels...
January 19, 2017: Neuro-oncology
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