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Pediatric brain cancer

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Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in ∼10% of cases. These MET fusions activated mitogen-activated protein kinase (MAPK) signaling and, in cooperation with lesions compromising cell cycle regulation, induced aggressive glial tumors in vivo. MET inhibitors suppressed MET tumor growth in xenograft models...
October 17, 2016: Nature Medicine
Heather Marion Ames, Ming Yuan, Maria Adelita Vizcaíno, Wayne Yu, Fausto J Rodriguez
Low-grade (WHO I-II) gliomas and glioneuronal tumors represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression/translation that can repress multiple mRNAs concurrently through base pairing, and have an important role in cancer, including brain tumors...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Shanghao Li, Daniel Amat, Zhili Peng, Steven Vanni, Scott Raskin, Guillermo De Angulo, Abdelhameed M Othman, Regina M Graham, Roger M Leblanc
Among various cancers, pediatric brain tumors represent the most common cancer type in children and the second most common cause of cancer related deaths. Anticancer drugs and therapies, such as doxorubicin (Dox), have severe side effects on patients during chemotherapy, especially for children as their bodies are still under development. These side effects are believed to be due to the lack of a delivery system with high efficacy and targeting selectivity, resulting in serious damages of normal cells. To improve the efficacy and selectivity, the transferrin (Trans) receptor mediated endocytosis can be utilized for drug delivery system design, as transferrin receptors are expressed on the blood brain barrier (BBB) and often over expressed in brain tumor cells...
September 22, 2016: Nanoscale
Hee Jung Yoo, Hyery Kim, Hyeon Jin Park, Dong Seok Kim, Young Shin Ra, Hee Young Shin
The neurocognitive function and quality of life of 58 Korean survivors of childhood medulloblastoma were assessed after surgery, cranial radiation and chemotherapy. All patients were evaluated with a battery of neurocognitive function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain Tumor Survivors, which consists of self-report questionnaires on quality of life. The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ scores were 90.2, 97.1, and 84.16, respectively...
November 2016: Journal of Korean Medical Science
Annette Weiss, Grit Sommer, Rahel Kasteler, Katrin Scheinemann, Michael Grotzer, Martin Kompis, Claudia E Kuehni
BACKGROUND: Auditory complications are an adverse event of childhood cancer treatment, especially common in children treated with platinum chemotherapy or cranial radiation. Variation between diagnostic childhood cancer groups has rarely been studied, and we do not know if the burden of auditory complications has changed over the last decades. PROCEDURE: Within the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all survivors who were diagnosed at age 16 years or less between 1976 and 2005...
September 21, 2016: Pediatric Blood & Cancer
Vahan Martirosian, Thomas C Chen, Michelle Lin, Josh Neman
Medulloblastomas are the most common malignant pediatric brain tumors. Over the past several decades, a wide range of tumor-centric studies have identified genes and their regulators within signaling pathways that promote medulloblastoma growth. This review aims to raise awareness that transdisciplinary research between developmental neurobiology and cancer foundations can advance our current understanding of how the nervous system contributes to medulloblastomas. By leveraging current advances in neurodevelopment, microenvironment (including secreted neuropeptides), neurotransmitters, and axon guidance cues, we can uncover novel mechanisms used by the nervous system to promote medulloblastoma growth and spread...
December 2016: Journal of Neuroscience Research
Barbara Tanno, Gabriele Babini, Simona Leonardi, Paola Giardullo, Ilaria De Stefano, Emanuela Pasquali, Andrea Ottolenghi, Michael J Atkinson, Anna Saran, Mariateresa Mancuso
It has historically been accepted that incorrectly repaired DNA double strand breaks (DSBs) are the principal lesions of importance regarding mutagenesis, and long-term biological effects associated with ionizing radiation. However, radiation may also cause dysregulation of epigenetic processes that can lead to altered gene function and malignant transformation, and epigenetic alterations are important causes of miRNAs dysregulation in cancer.Patched1 heterozygous (Ptch1+/-) mice, characterized by aberrant activation of the Sonic hedgehog (Shh) signaling pathway, are a well-known murine model of spontaneous and radiation-induced medulloblastoma (MB), a common pediatric brain tumor originating from neural granule cell progenitors (GCPs)...
September 10, 2016: Oncotarget
Hernán Correa
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a germline mutation of the TP53 gene on chromosome 17p13.1. It has an autosomal dominant pattern of inheritance with high penetrance. These patients have a very high lifetime cumulative risk of developing multiple malignancies and have a strong family history of early-onset malignancies. The protein p53, encoded by TP53, has a complex set of genome-preserving functions initiated during episodes of cellular stress and DNA damage. In LFS, TP53 gene mutations cause the loss of function of p53, leading to downstream events permissive for development of various malignancies throughout life...
June 2016: Journal of Pediatric Genetics
Emilyn Banfield, Austin L Brown, Erin C Peckham, Surya P Rednam, Jeffrey Murray, M Fatih Okcu, Laura E Mitchell, Murali M Chintagumpala, Ching C Lau, Michael E Scheurer, Philip J Lupo
AIM: Medulloblastoma is the most frequent malignant pediatric brain tumor. While survival rates have improved due to multimodal treatment including cisplatin-based chemotherapy, there are few prognostic factors for adverse treatment outcomes. Notably, genes involved in the nucleotide excision repair pathway, including ERCC2, have been implicated in cisplatin sensitivity in other cancers. Therefore, this study evaluated the role of ERCC2 DNA methylation profiles on pediatric medulloblastoma survival...
October 2016: Cancer Epidemiology
Martin G McCabe, Dominique Valteau-Couanet
Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood...
2016: Progress in Tumor Research
Harold Agbahiwe, Arif Rashid, Alena Horska, E Mark Mahone, Doris Lin, Todd McNutt, Kenneth Cohen, Kristin Redmond, Moody Wharam, Stephanie Terezakis
BACKGROUND: Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long-term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning. METHODS: Ten pediatric patients with primary brain tumors treated with cranial RT and 14 age- and sex-matched healthy children serving as controls were evaluated...
August 29, 2016: Cancer
Zinat Taiwo, Sabrina Na, Tricia Z King
OBJECTIVE: Prior research has demonstrated the reliability and validity of the Neurological Predictor Scale (NPS) in relation to intelligence and adaptive functioning in survivors of pediatric brain tumors. To extend these findings, this study examined the relationship between the NPS and core neurocognitive skills hypothesized to underlie broad outcome measures of IQ and adaptive functioning. METHOD: Sixty-one adulthood survivors of childhood brain cancers (Mage = 24 years, SD = 6) on average 16 years after diagnosis completed neuropsychological assessments examining attention (Wechsler Memory Scale Digit Span Forward), processing speed (Symbol Digit Modalities Test), and working memory (Auditory Consonant Trigrams)...
August 27, 2016: Pediatric Blood & Cancer
Kevin F Ginn, Ben Fangman, Kaoru Terai, Amanda Wise, Daniel Ziazadeh, Kushal Shah, Robyn Gartrell, Brandon Ricke, Kyle Kimura, Sharad Mathur, Emma Borrego-Diaz, Faris Farassati
Medulloblastoma (MDB) represents a major form of malignant brain tumors in the pediatric population. A vast spectrum of research on MDB has advanced our understanding of the underlying mechanism, however, a significant need still exists to develop novel therapeutics on the basis of gaining new knowledge about the characteristics of cell signaling networks involved. The Ras signaling pathway, one of the most important proto-oncogenic pathways involved in human cancers, has been shown to be involved in the development of neurological malignancies...
August 26, 2016: Journal of Neuro-oncology
Shu-Mei Chen, Ying-Ying Li, Chiao-Hui Tu, Nicole Salazar, Yuan-Yun Tseng, Shiang-Fu Huang, Ling-Ling Hsieh, Tai-Ngar Lui
BACKGROUND: Medulloblastoma (MB) is the most common pediatric primary malignant brain tumor. Approximately one-third of MB patients succumb to treatment failure and some survivors suffer detrimental side effects. Hence, the purpose of this study is to explore new therapeutic regimens to overcome chemotherapeutic agent resistance or reduce chemotherapy-induced toxicity. METHODS: We detected the expression of inhibitors of apoptosis proteins (IAPs) in MB and CD133+ MB cell lines and MB tissues using immunoblotting and immunohistochemical staining...
2016: PloS One
Victoria W Willard, Heather M Conklin, Lu Huang, Hui Zhang, Lisa S Kahalley
Survivors of childhood cancer are at risk for attention problems. The objectives of this study were to assess concordance between parent-, teacher-, and self-report ratings on a measure of attention (Conners Rating Scales, 3rd ed.; Conners, 2008) in adolescent survivors of childhood cancer and to examine associations with a performance-based task. The was completed by 80 survivors of pediatric cancer (39 brain tumor, 41 acute lymphoblastic leukemia; ages 12-17; at least 1 year posttreatment; 51.3% male) as well as their parents and 1 teacher...
September 2016: Psychological Assessment
Sarah A Hansen, Marcia L Hart, Susheel Busi, Taybor Parker, Angela Goerndt, Kevin Jones, James M Amos-Landgraf, Elizabeth C Bryda
Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease...
October 1, 2016: Disease Models & Mechanisms
Robert J Brown, Brandon J Jun, Jesse D Cushman, Christine Nguyen, Adam H Beighley, Johnny Blanchard, Kei Iwamoto, Dorthe Schaue, Neil G Harris, James D Jentsch, Stefan Bluml, William H McBride
PURPOSE: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. METHODS AND MATERIALS: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure...
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Cecilia Follin, Eva Marie Erfurth
Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL)...
September 2016: Current Treatment Options in Oncology
Heather Smith, AmiLyn Taplin, Sohail Syed, Matthew A Adamo
OBJECTIVE Malignant disease of the CNS is the primary etiology for deaths resulting from cancer in the pediatric population. It has been well documented that outcomes of pediatric neurosurgery rely on the extent of tumor resection. Therefore, techniques that improve surgical results have significant clinical implications. Intraoperative ultrasound (IOUS) offers real-time surgical guidance and a more accurate means for detecting residual tumor that is inconspicuous to the naked eye. The objective of this study was to evaluate the correlation of extent of resection between IOUS and postoperative MRI...
July 29, 2016: Journal of Neurosurgery. Pediatrics
Cory Pierson, Erin Waite, Ben Pyykkonen
BACKGROUND: Long-term neuropsychological deficits associated with pediatric cancers and the related treatments have been consistently reported. Whole brain cranial radiation therapy (CRT) is associated with neurocognitive impairment. As a result, physicians are reticent to use CRT in favor of systemic or intrathecal chemotherapy, which have a less clear impact on cognition. PROCEDURE: The current meta-analysis examined post-treatment neuropsychological performance of children diagnosed with cancer and treated with chemotherapy to better understand the impact of chemotherapy upon cognition...
November 2016: Pediatric Blood & Cancer
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