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Pediatric brain cancer

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https://www.readbyqxmd.com/read/28214639/congenital-glioblastoma-with-distinct-clinical-and-molecular-characteristics-case-reports-and-a-literature-review
#1
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
#2
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...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28186969/high-oct4a-levels-drive-tumorigenicity-and-metastatic-potential-of-medulloblastoma-cells
#3
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...
7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#4
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
#5
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
#6
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...
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28094001/autophagy-inhibition-overcomes-multiple-mechanisms-of-resistance-to-braf-inhibition-in-brain-tumors
#10
Jean M Mulcahy Levy, Shadi Zahedi, Andrea M Griesinger, Andrew Morin, Kurtis D Davies, Dara L Aisner, B K Kleinschmidt-DeMasters, Brent E Fitzwalter, Megan L Goodall, Jacqueline Thorburn, Vladimir Amani, Andrew M Donson, Diane K Birks, David M Mirsky, Todd C Hankinson, Michael H Handler, Adam L Green, Rajeev Vibhakar, Nicholas K Foreman, Andrew Thorburn
Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAF(V600E)mutations occur in many pediatric brain tumors. We previously reported that these tumors are autophagy-dependent and a patient was successfully treated with the autophagy inhibitor chloroquine after failure of the BRAF(V600E) inhibitor vemurafenib, suggesting autophagy inhibition overcame the kinase inhibitor resistance...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28069802/genomic-profiling-of-a-large-set-of-diverse-pediatric-cancers-identifies-known-and-novel-mutations-across-tumor-spectra
#11
Juliann Chmielecki, Mark Bailey, Jie He, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M Frampton, James X Sun, Samantha Morley, Daniel Spritz, Siraj Ali, Laurie Gay, Rachel L Erlich, Jeffrey S Ross, Joana Buxhaku, Hilary Davies, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A Miller, Philip J Stephens, Katherine A Janeway, John M Maris, Soheil Meshinchi, Trevor J Pugh, Jack F Shern, Doron Lipson
Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28068559/the-ageing-genome-clonal-mosaicism-and-chronic-disease
#12
REVIEW
Mitchell J Machiela, Stephen J Chanock
Clonal mosaicism arises when a postzygotic mutational event is detectable in subpopulations of cells as an alternative genotype while not present in the germline genome. Although described in a subset of pediatric disorders, new genomic technologies have detected higher than anticipated frequencies of clonal mosaicism in adult population studies, stimulating investigation as to how clonal mosaicism could contribute to chronic human diseases, such as cancer, diabetes and neurodegenerative disorders. It has also been postulated to be an important mechanism for functional cellular diversity, including the brain...
January 6, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28059591/epigenetic-modification-in-chromatin-machinery-and-its-deregulation-in-pediatric-brain-tumors-insight-into-epigenetic-therapies
#13
Eleonore Maury, Rintaro Hashizume
Malignancies are characterized by the reprogramming of epigenetic patterns. This reprogramming includes gains or losses in DNA methylation and disruption of normal patterns of covalent histone modifications, which are associated with changes in chromatin remodeling processes. This review will focus on the mechanisms underlying this reprogramming and, specifically, on the role of histone modification in chromatin machinery and the modifications in epigenetic processes occurring in brain cancer, with a specific focus on epigenetic therapies for pediatric brain tumors...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28052939/no-association-between-radiation-dose-from-pediatric-ct-scans-and-risk-of-subsequent-hodgkin-lymphoma
#14
Amy Berrington de Gonzalez, Neige Journy, Choonsik Lee, Lindsay M Morton, Richard Harbron, Douglas R Stewart, Louise Parker, Alan W Craft, Kieran McHugh, Mark Little, Mark Pearce
BACKGROUND: We examined the relationship between estimated radiation dose from CT scans and subsequent Hodgkin lymphoma in the UK pediatric CT scans cohort. METHODS: A retrospective, record linkage cohort included patients aged 0-21 years who underwent CT scans between 1980 and 2002 and were followed up for cancer or death until 2008. Poisson regression analysis was used to evaluate the relationship between estimated radiation dose (lagged by two years) and incident Hodgkin lymphoma diagnosed at least two years after the first CT scan...
January 4, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28046705/su-f-t-202-an-evaluation-method-of-lifetime-attributable-risk-for-comparing-between-proton-beam-therapy-and-intensity-modulated-x-ray-therapy-for-pediatric-cancer-patients-by-averaging-four-dose-response-models-for-carcinoma-induction
#15
M Tamura, Y Ito, H Sakurai, M Mizumoto, S Kamizawa, S Murayama, H Yamashita, S Takao, R Suzuki, H Shirato
PURPOSE: To examine how much lifetime attributable risk (LAR) as an in silico surrogate marker of radiation-induced secondary cancer would be lowered by using proton beam therapy (PBT) in place of intensity modulated x-ray therapy (IMXT) in pediatric patients. METHODS: From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: a) brain, head, and neck, b) thoracic, c) abdominal, and d) whole craniospinal (WCNS) irradiation...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28044936/nano-delivery-in-pediatric-tumors-looking-back-moving-forward
#16
Marta Colletti, Virginia Di Paolo, Angela Galardi, Giuseppe Maria Milano, Angela Mastronuzzi, Franco Locatelli, Angela Di Giannatale
Recent advances in the treatment of pediatric tumors led to an improvement of survival in this population. As a result, many pediatric survivors experience long-term effects that impact their quality of life. Therefore, it is extremely important to identify new treatment approaches that may target the tumor minimizing the drug-related side effects. Over the past 10 years, remarkable advances in nanomedicine have provided several potential tools for cancer treatment. Recently, there has been a growing interest towards therapeutic nanocarriers in the pediatric field, since they represent a new strategy to enhance the drug efficacy and reduce the toxicity...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28017613/developmental-regulation-of-mitochondrial-apoptosis-by-c-myc-governs-age-and-tissue-specific-sensitivity-to-cancer-therapeutics
#17
Kristopher A Sarosiek, Cameron Fraser, Nathiya Muthalagu, Patrick D Bhola, Weiting Chang, Samuel K McBrayer, Adam Cantlon, Sudeshna Fisch, Gail Golomb-Mello, Jeremy A Ryan, Jing Deng, Brian Jian, Chris Corbett, Marti Goldenberg, Joseph R Madsen, Ronglih Liao, Dominic Walsh, John Sedivy, Daniel J Murphy, Daniel Ruben Carrasco, Shenandoah Robinson, Javid Moslehi, Anthony Letai
It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 profiling, we find that mitochondria of many adult somatic tissues, including brain, heart, and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28017579/seizures-caused-by-brain-tumors-in-children
#18
Iván Sánchez Fernández, Tobias Loddenkemper
PURPOSE: To review the epidemiology, clinical features, and treatment of seizures secondary to pediatric brain tumors. METHOD: Literature review. RESULTS: Pediatric brain tumors are the most common solid pediatric tumor and the most common cause of death in pediatric cancer. Seizures are one of the most common symptoms of pediatric brain tumors. Factors associated with increased risk of seizures include supratentorial location, gray matter involvement, low-grade, and certain histological features-especially dysembryoplastic neuroepithelial tumor, ganglioglioma, and oligodendroglioma...
December 7, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28004469/long-term-follow-up-after-proton-beam-therapy-for-pediatric-tumors-a-japanese-national-survey
#19
Masashi Mizumoto, Shigeyuki Murayama, Tetsuo Akimoto, Yusuke Demizu, Takashi Fukushima, Yuji Ishida, Yoshiko Oshiro, Haruko Numajiri, Hiroshi Fuji, Toshiyuki Okumura, Hiroki Shirato, Sakurai Hideyuki
Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0-19 years) at the time of treatment...
December 22, 2016: Cancer Science
https://www.readbyqxmd.com/read/27978785/the-five-pediatric-cancers-update-on-genetic-implications
#20
Stacy Cooper, Jeffrey Rubens, Joann Bodurtha
Pediatric cancer has undergone significant improvements in survival over the past several decades, in part due to a better understanding of the underlying genetic aberrations of each oncologic diagnosis, which has allowed for more effective targeted therapies. Pediatric brain tumors, leukemia, lymphoma, Wilms tumor, and retinoblastoma are exemplary pediatric cancers that each have specific epidemiology regarding children at risk as well as characteristic associated genetic lesions. These genetic features are more commonly being used to provide risk stratification, as well as to identify novel pathways for targeted therapy...
December 13, 2016: Current Pediatric Reviews
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