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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
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
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
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...
July 20, 2016: Neuroradiology
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
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
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...
2016: Curēus
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
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
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...
June 14, 2016: Oncotarget
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
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
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
Sophie E M Veldhuijzen van Zanten, Ofelia Cruz, Gertjan J L Kaspers, Darren R Hargrave, Dannis G van Vuurden
Children diagnosed with diffuse intrinsic pontine glioma (DIPG) face a dismal prognosis, with severe neurologic deterioration and inevitable death at a median of 9 months from diagnosis. Steroids are widely prescribed as supportive or palliative treatment although they are known to cause severe side effects that may reduce the quality of life. This study aims to review the current knowledge on, and use of, steroids in DIPG patients. A global questionnaire-study among health care professionals was performed to ascertain information on the current (multi-)institutional and (multi-)national use of steroids, the availability of clinical guidelines, and the need for improvements in prescribing steroids to DIPG patients...
July 2016: Journal of Neuro-oncology
Tessa B Johung, Michelle Monje
BACKGROUND: Diffuse Intrinsic Pontine Glioma (DIPG) is the leading cause of brain tumor-related death in children, with median survival of less than one year. Despite decades of clinical trials, there has been no improvement in prognosis since the introduction of radiotherapy over thirty years ago. OBJECTIVE: To review the clinical features and current treatment challenges of DIPG, and discuss emerging insights into the unique genomic and epigenomic mechanisms driving DIPG pathogenesis that present new opportunities for identification of therapeutic targets...
May 9, 2016: Current Neuropharmacology
M Wiese, F Schill, D Sturm, S Pfister, E Hulleman, S A Johnsen, C M Kramm
BACKGROUND: Glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) belong to the most aggressive cancers in children with poor prognosis and limited therapeutic options. Therapeutic targeting of epigenetic proteins may offer new treatment options. Preclinical studies identified Enhancer of Zeste Homolog 2 (EZH2) within polycomb repressor complex 2 (PRC2) as a potential epigenetic anti-tumor target in adult GBM cells but similar inhibition studies in pediatric GBM/DIPG were still missing...
April 2016: Klinische Pädiatrie
Libby Kosnik Infinger, Charles B Stevenson
Diffuse intrinsic pontine glioma (DIPG) is a malignant brain tumor of childhood that carries an extremely poor prognosis. There are ~200-300 new cases diagnosed each year, [1,2] and little progress has been made in changing the prognosis and outcome of the tumor since it was first documented in the literature in 1926 [3]. The median overall survival is 8-11 months [4], with an overall survival rate of 30% at 1 year, and less than 10% at 2 years [4]. This review will provide background information on DIPGs, a historical look at the trends in caring for DIPG, and current trends in diagnosis and treatment...
April 25, 2016: Current Neuropharmacology
Jamie Tisnado, Robert Young, Kyung K Peck, Sofia Haque
Diffuse intrinsic pontine glioma is the most common brainstem tumor in pediatric patients. This tumor remains one of the most deadly pediatric brain tumors. The diagnosis primarily relies on clinical symptoms and imaging findings. Conventional MRI provides a noninvasive accurate method of diagnosis of these tumors. Advanced MRI techniques are becoming more widely used and studied as additional noninvasive methods to assist clinicians in initial diagnosis and staging, monitoring disease, as well as in surgical and radiation planning...
October 2016: Journal of Child Neurology
Hamid Nikbakht, Eshini Panditharatna, Leonie G Mikael, Rui Li, Tenzin Gayden, Matthew Osmond, Cheng-Ying Ho, Madhuri Kambhampati, Eugene I Hwang, Damien Faury, Alan Siu, Simon Papillon-Cavanagh, Denise Bechet, Keith L Ligon, Benjamin Ellezam, Wendy J Ingram, Caedyn Stinson, Andrew S Moore, Katherine E Warren, Jason Karamchandani, Roger J Packer, Nada Jabado, Jacek Majewski, Javad Nazarian
Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M--including H3.2K27M--mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis...
2016: Nature Communications
Amy Lee Bredlau, Suraj Dixit, Chao Chen, Ann Marie Broome
Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs...
February 23, 2016: Current Neuropharmacology
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