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Pediatric brain cancer

Dario Presutti, Manuela Ceccarelli, Laura Micheli, Giuliana Papoff, Simonetta Santini, Simone Samperna, Cristiana Lalli, Lorena Zentilin, Giovina Ruberti, Felice Tirone
Medulloblastoma (MB), the tumor of the cerebellum, is the most frequent brain cancer in childhood and a major cause of pediatric mortality. Based on gene profiling, four MB subgroups have been identified, i.e., Wnt or Sonic Hedgehog (Shh) types, and subgroup 3 or 4. The Shh-type MB has been shown to arise from the cerebellar precursors of granule neurons (GCPs), where a hyperactivation of the Shh pathway leads to their neoplastic transformation. We have previously shown that the gene Tis21 (PC3/Btg2) inhibits the proliferation and promotes the differentiation and migration of GCPs...
2018: PloS One
Alexandra Garancher, Charles Y Lin, Morgane Morabito, Wilfrid Richer, Nathalie Rocques, Magalie Larcher, Laure Bihannic, Kyle Smith, Catherine Miquel, Sophie Leboucher, Nirmitha I Herath, Fanny Dupuy, Pascale Varlet, Christine Haberler, Christine Walczak, Nadine El Tayara, Andreas Volk, Stéphanie Puget, François Doz, Olivier Delattre, Sabine Druillennec, Olivier Ayrault, Robert J Wechsler-Reya, Alain Eychène, Franck Bourdeaut, Paul A Northcott, Celio Pouponnot
Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes to malignancy is poorly understood. An aggressive subgroup of medulloblastoma, a malignant pediatric brain tumor of the cerebellum, expresses a photoreceptor differentiation program normally expressed in the retina. We establish that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup...
March 12, 2018: Cancer Cell
L Holmes, P Chavan, T Blake, K Dabney
BACKGROUND: While survival in overall pediatric malignancy has improved during recent decades, brain/central nervous system (CNS) tumors has not demonstrated comparable survival advantage. Incidence and mortality data in this malignancy continue to illustrate race and sex differences; however, there are few data in the pediatric setting. This study sought to characterize brain/CNS tumors by socio-demographic and assess racial and sex variances in both cumulative incidence and mortality...
March 7, 2018: Journal of Racial and Ethnic Health Disparities
Xiaolin Li, Zhangning Zhao, Xiaomin Liu, Gaoting Ma, Mei-Jia Zhu
INTRODUCTION: Propofol infusion syndrome (PRIS) is a rare but potentially fatal complication of propofol infusion. It is clinically characterized by metabolic acidosis, refractory bradycardia, rhabdomyolysis, renal failure, hyperlipidemia, and hepatomegaly. Brain lesion was only reported once in a pediatric patient. We present the 1st adult case with colon polyp and cancer who was diagnosed with PRIS. Her brain magnetic resonance imaging (MRI) and computed tomography (CT) scans reveal prominent bilateral brain lesions, matching with the proposed pathophysiologic mechanism of the syndrome...
January 2018: Medicine (Baltimore)
Fatima Tensaouti, Anne Ducassou, Léonor Chaltiel, Annick Sevely, Stéphanie Bolle, Laetitia Padovani, Anais Jouin, Claire Alapetite, Stéphane Supiot, Aymeri Huchet, Valérie Bernier, Line Claude, Christine Kerr, Elisabeth Le Prisé, Anne-Isabelle Bertozzi-Salamon, Samuel Liceaga, Jean Albert Lotterie, Patrice Péran, Anne Laprie
BACKGROUND AND PURPOSE: Ependymoma is the third most common brain tumor in children. Radiation therapy (RT) is systematically administered after maximum surgical resection, utilizing recent advances in radiation delivery. Imaging can make a significant contribution to improving treatment outcome. This prompted us to look for significant preoperative and postoperative imaging markers for survival. MATERIAL AND METHODS: We undertook a national retrospective review of 121 patients who had undergone resection followed by RT...
February 27, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Andrew H Zureick, Casey L Evans, Andrzej Niemierko, Julie A Grieco, Alexandra J Nichols, Barbara C Fullerton, Clayton B Hess, Claire P Goebel, Sara L Gallotto, Elizabeth A Weyman, Dillon E Gaudet, Jessica A Nartowicz, David H Ebb, Robin M Jones, Shannon M MacDonald, Nancy J Tarbell, Torunn I Yock, Margaret B Pulsifer
BACKGROUND: Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT). METHODS: A total of 70 patients (median age at PRT, 12.1 years [range, 5.0-22.5 years]) who were treated with PRT were identified with baseline and follow-up evaluations of visual and verbal memory (Children's Memory Scale and the third edition of the Wechsler Memory Scale)...
March 2, 2018: Cancer
Maria Tsoli, Jie Liu, Laura Franshaw, Han Shen, Cecilia Cheng, MoonSun Jung, Swapna Joshi, Anahid Ehteda, Aaminah Khan, Angel Montero-Carcabosso, Pierre J Dilda, Philip Hogg, David S Ziegler
Diffuse Intrinsic Pontine Gliomas (DIPG) are the most devastating of all pediatric brain tumors. They mostly affect young children and, as there are no effective treatments, almost all patients with DIPG will die of their tumor within 12 months of diagnosis. A key feature of this devastating tumor is its intrinsic resistance to all clinically available therapies. It has been shown that glioma development is associated with metabolic reprogramming, redox state disruption and resistance to apoptotic pathways...
January 26, 2018: Oncotarget
Paul Gibson, Jason D Pole, Tanya Lazor, Donna Johnston, Carol Portwine, Mariana Silva, Sarah Alexander, Lillian Sung
Using a previously developed reliable and valid treatment-related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population-based cohort. We included children with cancer <19 years diagnosed and treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer were identified using data in a provincial registry. Cumulative incidence of TRM was calculated where progressive disease death was considered a competing event...
February 23, 2018: Cancer Medicine
Michelle S Gentile, Beow Y Yeap, Harald Paganetti, Claire P Goebel, Dillon E Gaudet, Sara L Gallotto, Elizabeth A Weyman, Michael L Morgan, Shannon M MacDonald, Drosoula Giantsoudi, Judith Adams, Nancy J Tarbell, Hanne Kooy, Torunn I Yock
PURPOSE: Proton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution. METHODS AND MATERIALS: The study included 216 consecutive patients treated between 2000 and 2015...
March 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Miranda L Camet, Susan S Hayashi, Belinda C Sinks, Jennifer Henry, Katie Gettinger, Ashley Hite, Juliann Kiefer, Caroline Mohrmann, Taryn Sandheinrich, Feng Gao, Robert J Hayashi
BACKGROUND: Sensorineural hearing loss due to ototoxic cancer therapy is well established; effects on the vestibular system are unknown. We examined the feasibility of implementing vestibular screens for pediatric cancer survivors exposed to ototoxic agents. The prevalence of screening failures is reported. METHODS: Cancer survivors who were 6-17 years, at least 1-month posttreatment, and received ototoxic therapy (radiation to the head/neck, cisplatin, carboplatin) were eligible...
January 30, 2018: Pediatric Blood & Cancer
Margaret Stromecki, Nazanin Tatari, Ludivine Coudière Morrison, Ravinder Kaur, Jamie Zagozewski, Gareth Palidwor, Vijay Ramaswamy, Patryk Skowron, Matthias Wölfl, Till Milde, Marc R Del Bigio, Michael D Taylor, Tamra Werbowetski-Ogilvie
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor initiation from MB stem/progenitor cells in vivo...
January 27, 2018: Molecular Oncology
Barrett Allen, Munjal M Acharya, Celine Lu, Erich Giedzinski, Nicole Chmielewski, David Quach, Mike Hefferan, Karl K Johe, Charles L Limoli
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments...
January 19, 2018: Radiation Research
Kris Ann P Schultz, Gretchen M Williams, Junne Kamihara, Douglas R Stewart, Anne K Harris, Andrew J Bauer, Joyce Turner, Rachana Shah, Katherine Schneider, Kami Wolfe Schneider, Ann Garrity Carr, Laura A Harney, Shari Baldinger, A Lindsay Frazier, Daniel Orbach, Dominik T Schneider, David Malkin, Louis P Dehner, Yoav H Messinger, Ashley Hill
Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline DICER1 variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma and brain tumors including pineoblastoma and pituitary blastoma...
January 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Simone Treiger Sredni, Anders W Bailey, Amreena Suri, Rintaro Hashizume, Xingyao He, Nundia Louis, Tufan Gokirmak, David R Piper, Daniel M Watterson, Tadanori Tomita
Rhabdoid tumors (RT) are highly aggressive and vastly unresponsive embryonal tumors. They are the most common malignant CNS tumors in infants below 6 months of age. Medulloblastomas (MB) are embryonal tumors that arise in the cerebellum and are the most frequent pediatric malignant brain tumors. Despite the advances in recent years, especially for the most favorable molecular subtypes of MB, the prognosis of patients with embryonal tumors remains modest with treatment related toxicity dreadfully high. Therefore, new targeted therapies are needed...
December 19, 2017: Oncotarget
Gang Xu, Ying Chen, Jie Liu, Shi-Wei Liu, Ping Wang, Jing Yang, Jiu-Ling Huang
OBJECTIVE: To study the burden of pediatric cancer in Jiangxi, China, in 2010 and 2015 and its changes from 2010 to 2015. METHODS: The data of pediatric cancer in Jiangxi in 2010 and 2015 were collected from the Global Burden of Disease Study 2015 in China, including number of cases, number of deaths, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). The standardized incidence rate, mortality rate, and DALY rate were calculated with the national census data in 2010 as the standard population, in order to evaluate the changes in incidence, mortality, and disease burden of pediatric cancer in Jiangxi...
January 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Nicole A P Lieberman, Nicholas A Vitanza, Courtney A Crane
Adverse effects and toxicities related to standard treatments for brain tumors significantly reduce patients' quality of life. Although most immunotherapy approaches for solid tumors have not been successful, several early-phase clinical trials are beginning to reveal a potential role for immunotherapy in the treatment of brain tumors. In particular, methods that activate the innate immune system and induce a polyclonal anti-cancer response have demonstrated that brain tumors are susceptible to immune-mediated tumor destruction...
January 11, 2018: Expert Review of Neurotherapeutics
Ana S Guerreiro Stucklin, Vijay Ramaswamy, Craig Daniels, Michael D Taylor
PURPOSE OF REVIEW: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors...
February 2018: Current Opinion in Pediatrics
Valentin Benzing, Noëmi Eggenberger, Janine Spitzhüttl, Valerie Siegwart, Manuela Pastore-Wapp, Claus Kiefer, Nedelina Slavova, Michael Grotzer, Theda Heinks, Mirko Schmidt, Achim Conzelmann, Maja Steinlin, Regula Everts, Kurt Leibundgut
BACKGROUND: Cancer survival comes at a price: pediatric cancer survivors bear a high risk for a wide range of cognitive difficulties. Therefore, interventions targeting these difficulties are required. The aim of the present clinical trial is to extend empirical evidence about efficacy of cognitive and physical training in pediatric cancer survivors. It is hypothesized that early cognitive and physical interventions affect the remediation of pediatric cancer survivors in terms of improved executive functions (primary outcome)...
January 3, 2018: BMC Cancer
Tanner M Johanns, Cole J Ferguson, Patrick M Grierson, Sonika Dahiya, George Ansstas
BRAF V600E mutations have been successfully treated with targeted therapy in melanoma, non-small cell lung cancer, and thyroid cancer. Interestingly, these mutations have also been identified in a subset of pediatric and adult brain tumors, with several cases reportedly responding to targeted therapy. However, these reports have been limited to single-agent BRAF inhibitor therapy and recurrent disease. Herein, we report dramatic clinical and radiographic responses to combination dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) in 2 adults with high-grade gliomas (HGGs), with 1 patient treated in the first-line setting...
January 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Sutapa Ray, Don W Coulter, Shawn D Gray, Jason A Sughroue, Shrabasti Roychoudhury, Erin M McIntyre, Nagendra K Chaturvedi, Kishor K Bhakat, Shantaram S Joshi, Timothy R McGuire, John G Sharp
Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors...
December 27, 2017: Molecular Carcinogenesis
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