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Diffuse Intrinsic Pontine Glioma

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https://www.readbyqxmd.com/read/27765855/molecular-drug-imaging-89zr-bevacizumab-pet-in-children-with-diffuse-intrinsic-pontine-glioma
#1
Marc Jansen, Sophie Em Veldhuijzen van Zanten, Dannis G Van Vuurden, Marc Huisman, Danielle J Vugts, Otto S Hoekstra, Guus A M S van Dongen, Gert-Jan Jl Kaspers
: Predictive tools to guide therapy in children with brain tumors are urgently needed. We introduced molecular imaging to facilitate this. We investigated whether bevacizumab can reach the tumor in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of zirconium-89((89)Zr)-labeled bevacizumab by PET. In addition we evaluated the safety of the procedure in children and determined the optimal timing of imaging. METHODS: Patients received 0...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27713169/a-phase-1-study-of-oral-ridaforolimus-in-pediatric-patients-with-advanced-solid-tumors
#2
Andrew D J Pearson, Sara M Federico, Isabelle Aerts, Darren R Hargrave, Steven G DuBois, Robert Iannone, Ryan D Geschwindt, Ruixue Wang, Frank G Haluska, Tanya M Trippett, Birgit Geoerger
PURPOSE: Ridaforolimus is an investigational, potent, selective mTOR inhibitor. This study was conducted to determine the recommended phase 2 dose (RP2D), maximum tolerated dose, safety, pharmacokinetics, and antitumor activity of oral ridaforolimus in children with advanced solid tumors. EXPERIMENTAL DESIGN: In this phase 1, multicenter, open-label study in children aged 6 to <18 years with advanced solid tumors, ridaforolimus was administered orally for 5 consecutive days/week in 28-day cycles until progression, unacceptable toxicity, or consent withdrawal...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27698822/bioinformatics-analysis-of-the-molecular-mechanism-of-diffuse-intrinsic-pontine-glioma
#3
Lei Deng, Pengju Xiong, Yunhui Luo, Xiao Bu, Suokai Qian, Wuzhao Zhong
The present study aimed to elucidate key molecular mechanisms in the progression of diffuse intrinsic pontine glioma (DIPG). The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in the pediatric DIPG samples were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways of DEGs were enriched and analyzed. The protein-protein interaction (PPI) network of the DEGs was constructed and functional modules of the PPI network were disclosed using ClusterONE...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27538997/polo-like-kinase%C3%A2-1-as-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#4
Vladimir Amani, Eric W Prince, Irina Alimova, Ilango Balakrishnan, Diane Birks, Andrew M Donson, Peter Harris, Jean M Mulcahy Levy, Michael Handler, Nicholas K Foreman, Sujatha Venkataraman, Rajeev Vibhakar
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive, fatal, childhood tumors that arise in the brainstem. DIPGs have no effective treatment, and their location and diffuse nature render them inoperable. Radiation therapy remains the only standard of care for this devastating disease. New therapeutic targets are needed to develop novel therapy for DIPG. METHODS: We examined the expression of PLK1 mRNA in DIPG tumor samples through microarray analysis and found it to be up regulated versus normal pons...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27438806/discrepant-longitudinal-volumetric-and-metabolic-evolution-of-diffuse-intrinsic-pontine-gliomas-during-treatment-implications-for-current-response-assessment-strategies
#5
U Löbel, S Hwang, A Edwards, Y Li, X Li, A Broniscer, Z Patay
INTRODUCTION: Based on clinical observations, we hypothesized that in infiltrative high-grade brainstem neoplasms, such as diffuse intrinsic pontine glioma (DIPG), longitudinal metabolic evaluation of the tumor by magnetic resonance spectroscopy (MRS) may be more accurate than volumetric data for monitoring the tumor's biological evolution during standard treatment. METHODS: We evaluated longitudinal MRS data and corresponding tumor volumes of 31 children with DIPG...
October 2016: Neuroradiology
https://www.readbyqxmd.com/read/27422681/diffuse-intrinsic-pontine-glioma-in-children-document-or-treat
#6
Beuriat Pierre-Aurélien, Szathmari Alexandru, Di Rocco Federico, Kanold Justyna, Mottolese Carmine, Frappaz Didier
BACKGROUND: The place of stereotactic biopsies in the management of diffuse intrinsic pontine gliomas (DIPGs) in children has changed over the years. Nonetheless, stereotactic biopsy remains a surgical procedure with its risks. One complication that has not been reported previously in case of a biopsy of a DIPG is metastatic seeding along the tract of the biopsy. We report the first 2 cases in the literature. CASE DESCRIPTION: One 8-year-old and one 9-year-old boy were admitted for a typical DIPG...
September 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27392443/pediatric-thalamic-glioma-with-h3f3a-k27m-mutation-which-was-detected-before-and-after-malignant-transformation-a-case-report
#7
Kenichi Ishibashi, Takeshi Inoue, Hiroko Fukushima, Yusuke Watanabe, Yoshiyasu Iwai, Hiroaki Sakamoto, Kai Yamasaki, Jyunichi Hara, Tomoko Shofuda, Daiksuke Kanematsu, Ema Yoshioka, Yonehiro Kanemura
PURPOSE: Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery...
December 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27391980/a-novel-magnetic-resonance-imaging-segmentation-technique-for-determining-diffuse-intrinsic-pontine-glioma-tumor-volume
#8
Ranjodh Singh, Zhiping Zhou, Jamie Tisnado, Sofia Haque, Kyung K Peck, Robert J Young, Apostolos John Tsiouris, Sunitha B Thakur, Mark M Souweidane
OBJECTIVE Accurately determining diffuse intrinsic pontine glioma (DIPG) tumor volume is clinically important. The aims of the current study were to 1) measure DIPG volumes using methods that require different degrees of subjective judgment; and 2) evaluate interobserver agreement of measurements made using these methods. METHODS Eight patients from a Phase I clinical trial testing convection-enhanced delivery (CED) of a therapeutic antibody were included in the study. Pre-CED, post-radiation therapy axial T2-weighted images were analyzed using 2 methods requiring high degrees of subjective judgment (picture archiving and communication system [PACS] polygon and Volume Viewer auto-contour methods) and 1 method requiring a low degree of subjective judgment (k-means clustering segmentation) to determine tumor volumes...
July 8, 2016: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/27382528/bromodomain-inhibitor-review-bromodomain-and-extra-terminal-family-protein-inhibitors-as-a-potential-new-therapy-in-central-nervous-system-tumors
#9
REVIEW
Elizabeth Wadhwa, Theodore Nicolaides
The bromodomain and extraterminal (BET) family proteins associate with transcriptional activation through interaction with acetylated chromatin, therefore playing a key role as epigenetic regulators. BET proteins serve to regulate the expression of importance oncogenes, including those involved in apoptosis as well as cell cycle progression. Due to this potential as an epigenetic target, small molecule inhibition of BET proteins have been investigated and demonstrate promising activity in both solid and hematologic malignancies, including brain tumors...
May 21, 2016: Curēus
https://www.readbyqxmd.com/read/27379495/pre-radiation-chemotherapy-improves-survival-in-pediatric-diffuse-intrinsic-pontine-gliomas
#10
Z Gokce-Samar, P A Beuriat, C Faure-Conter, C Carrie, S Chabaud, L Claude, F Di Rocco, C Mottolese, A Szathmari, C Chabert, D Frappaz
BACKGROUND: The median survival of patients with diffuse intrinsic pontine glioma (DIPG) remains less than 1 year. The BSG 98 pre-irradiation chemotherapy protocol showed a significant increase in overall survival. In contrast to current treatment strategies, patients did not have to undergo surgical stereotactic biopsy, which can sometimes lead to complications, to be included in this protocol. MATERIALS AND METHODS: We retrospectively reviewed all the cases of DIPG that were treated in our department from September 15, 2004 to September 15, 2014...
August 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27350411/a-molecular-biology-and-phase-ii-study-of-imetelstat-grn163l-in-children-with-recurrent-or-refractory-central-nervous-system-malignancies-a-pediatric-brain-tumor-consortium-study
#11
Ralph Salloum, Trent R Hummel, Shiva Senthil Kumar, Kathleen Dorris, Shaoyu Li, Tong Lin, Vinay M Daryani, Clinton F Stewart, Lili Miles, Tina Young Poussaint, Charles Stevenson, Stewart Goldman, Girish Dhall, Roger Packer, Paul Fisher, Ian F Pollack, Maryam Fouladi, James Boyett, Rachid Drissi
Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, high-grade glioma (HGG) or ependymoma undergoing resection received one dose of imetelstat as a 2-h intravenous infusion at 285 mg/m(2), 12-24 h before surgery...
September 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27344555/children-with-minimal-chance-for-cure-parent-proxy-of-the-child-s-health-related-quality-of-life-and-the-effect-on-parental-physical-and-mental-health-during-treatment
#12
Belinda N Mandrell, Justin Baker, Deena Levine, Jami Gattuso, Nancy West, April Sykes, Amar Gajjar, Alberto Broniscer
To assess health-related quality of life (HRQOL) from the time of diagnosis until disease progression in a cohort of children with diffuse intrinsic pontine glioma (DIPG). The assessment was collected from the perspectives of the child and their parents and evaluated the effect of the child's HRQOL on their parents' physical and mental well-being, thus providing insight into the optimal timing of palliative consultation, including anticipatory grief and bereavement services. This longitudinal study assessed 25 parents and their children, ages 2-17 years of age with DIPG across five time-points, baseline and weeks 2, 4, 6, 16, 24...
September 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27329600/histological-and-molecular-analysis-of-a-progressive-diffuse-intrinsic-pontine-glioma-and-synchronous-metastatic-lesions-a-case-report
#13
Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, L Gilbert Vezina, Roger J Packer, Eugene I Hwang
There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27327773/adult-brainstem-gliomas
#14
REVIEW
Sylvia C Eisele, David A Reardon
Brainstem gliomas in adults are a rare and heterogeneous group of brain tumors that vary with regard to underlying pathology, radiographic appearance, clinical course and prognosis. Diffuse intrinsic pontine gliomas represent the most common subtype. Although still considered aggressive and most often lethal, these brain tumors are associated with a more insidious clinical course and more favorable prognosis compared to the highly aggressive form in children. Treatment options for patients with brainstem gliomas still are limited and insufficiently studied...
September 15, 2016: Cancer
https://www.readbyqxmd.com/read/27325687/bevacizumab-targeting-diffuse-intrinsic-pontine-glioma-results-of-89zr-bevacizumab-pet-imaging-in-brain-tumor-models
#15
Marc H A Jansen, Tonny Lagerweij, A Charlotte P Sewing, Danielle J Vugts, Dannis G van Vuurden, Carla F M Molthoff, Viola Caretti, Susanna J E Veringa, Naomi Petersen, Angel M Carcaboso, David P Noske, W Peter Vandertop, Pieter Wesseling, Guus A M S van Dongen, Gertjan J L Kaspers, Esther Hulleman
The role of the VEGF inhibitor bevacizumab in the treatment of diffuse intrinsic pontine glioma (DIPG) is unclear. We aim to study the biodistribution and uptake of zirconium-89 ((89)Zr)-labeled bevacizumab in DIPG mouse models. Human E98-FM, U251-FM glioma cells, and HSJD-DIPG-007-FLUC primary DIPG cells were injected into the subcutis, pons, or striatum of nude mice. Tumor growth was monitored by bioluminescence imaging (BLI) and visualized by MRI. Seventy-two to 96 hours after (89)Zr-bevacizumab injections, mice were imaged by positron emission tomography (PET), and biodistribution was analyzed ex vivo High VEGF expression in human DIPG was confirmed in a publically available mRNA database, but no significant (89)Zr-bevacizumab uptake could be detected in xenografts located in the pons and striatum at an early or late stage of the disease...
September 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27251074/in-silico-analysis-of-histone-h3-gene-expression-during-human-brain-development
#16
Megan Ren, Steve van Nocker
Precise regulation of chromatin structure is essential for proper development of higher eukaryotes, and methylation of histone H3 at lysine-27 (H3K27) by the Polycomb Repressive Complex 2 (PRC2) component EZH2 has emerged as an important and conserved mechanism to ensure silencing of developmentally regulated genes. Recurrent mutations within the histone H3 genes H3F3A and HIST1H3B that convert K27 to methionine (H3K27M) and disrupt the global H3K27 methylation landscape and PRC2-dependent silencing, have recently been identified in pediatric high-grade gliomas including Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma multiforme (GBM; Type IV glioma)...
2016: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/27213425/pediatric-and-adult-high-grade-glioma-stem-cell-culture-models-are-permissive-to-lytic-infection-with-parvovirus-h-1
#17
Rafael Josupeit, Sebastian Bender, Sonja Kern, Barbara Leuchs, Thomas Hielscher, Christel Herold-Mende, Jörg R Schlehofer, Christiane Dinsart, Olaf Witt, Jean Rommelaere, Jeannine Lacroix
Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma...
2016: Viruses
https://www.readbyqxmd.com/read/27212051/patient-derived-tumor-models-for-diffuse-intrinsic-pontine-gliomas
#18
Rintaro Hashizume, Nalin Gupta
Diffuse intrinsic pontine gliomas represent a unique subtype of primary brain tumors occuring in a specific location and age. Their growth demonstrates early invasion and, following diagnosis, rapid growth not responsive to common therapies. Until recently, the genetic and cellular basis of these tumors was unknown. Genetic evidence implicates mutations in the histone genes in the origin of these tumors. Surgical biopsies performed on select patients has resulted in the establishment of anatomically accurate mouse models that have been used to examine patterns of growth and response to new therapeutic agents...
May 23, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27197987/mri-evaluation-of-non-necrotic-t2-hyperintense-foci-in-pediatric-diffuse-intrinsic-pontine-glioma
#19
O Clerk-Lamalice, W E Reddick, X Li, Y Li, A Edwards, J O Glass, Z Patay
BACKGROUND AND PURPOSE: The conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma. MATERIALS AND METHODS: Twenty-five patients with diffuse intrinsic pontine gliomas were included in this study...
May 19, 2016: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/27180091/pseudoprogression-in-children-adolescents-and-young-adults-with-non-brainstem-high-grade-glioma-and-diffuse-intrinsic-pontine-glioma
#20
Fernando Carceller, Lucy A Fowkes, Komel Khabra, Lucas Moreno, Frank Saran, Anna Burford, Alan Mackay, David T W Jones, Volker Hovestadt, Lynley V Marshall, Sucheta Vaidya, Henry Mandeville, Neil Jerome, Leslie R Bridges, Ross Laxton, Safa Al-Sarraj, Stefan M Pfister, Martin O Leach, Andrew D J Pearson, Chris Jones, Dow-Mu Koh, Stergios Zacharoulis
Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1-21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival...
August 2016: Journal of Neuro-oncology
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