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Diffuse intrinsic pontine glioma ( DIPG )

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https://read.qxmd.com/read/30771760/pontine-tumor-in-a-neonate-case-report-and-analysis-of-the-current-literature
#1
Constanze Buus-Gehrig, Thomas Lehrnbecher, Luciana Porto, Martina Becker, Thomas Freiman, Michel Mittelbronn, Konrad Bochennek
Tumors of the central nervous system represent the largest group of solid tumors found in pediatric patients. Pilocytic astrocytoma is the most common pediatric glioma, mostly located in the posterior fossa. The majority of brainstem tumors, however, are classified as highly aggressive diffuse intrinsic pontine gliomas (DIPGs) and their prognosis is dismal.The authors report on the case of a neonate in whom MRI and neuropathological assessment were used to diagnose DIPG. Before initiation of the planned chemotherapy, the tumor regressed spontaneously, and the newborn exhibited a normal neurological development...
February 15, 2019: Journal of Neurosurgery. Pediatrics
https://read.qxmd.com/read/30770999/h3-3-k27m-depletion-increases-differentiation-and-extends-latency-of-diffuse-intrinsic-pontine-glioma-growth-in-vivo
#2
André B Silveira, Lawryn H Kasper, Yiping Fan, Hongjian Jin, Gang Wu, Timothy I Shaw, Xiaoyan Zhu, Jon D Larson, John Easton, Ying Shao, Donald A Yergeau, Celeste Rosencrance, Kristy Boggs, Michael C Rusch, Liang Ding, Junyuan Zhang, David Finkelstein, Rachel M Noyes, Brent L Russell, Beisi Xu, Alberto Broniscer, Cynthia Wetmore, Stanley B Pounds, David W Ellison, Jinghui Zhang, Suzanne J Baker
Histone H3 K27M mutation is the defining molecular feature of the devastating pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). The prevalence of histone H3 K27M mutations indicates a critical role in DIPGs, but the contribution of the mutation to disease pathogenesis remains unclear. We show that knockdown of this mutation in DIPG xenografts restores K27M-dependent loss of H3K27me3 and delays tumor growth. Comparisons of matched DIPG xenografts with and without K27M knockdown allowed identification of mutation-specific effects on the transcriptome and epigenome...
February 15, 2019: Acta Neuropathologica
https://read.qxmd.com/read/30706132/diffuse-intrinsic-pontine-glioma-ventricular-peritoneal-shunt-metastasis-a-case-report-and-literature-review
#3
Chloé Louise Gelder, Cynthia Hawkins, Michal Zapotocky, Peter Dirks, Ute Bartels, Eric Bouffet
Dissemination of diffuse intrinsic pontine glioma (DIPG) outside the central nervous system is exceptional. Here, we present a child diagnosed with DIPG who developed seeding along the track of the ventriculoperitoneal shunt and review the literature on this unusual occurrence.
January 31, 2019: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://read.qxmd.com/read/30647848/detection-of-histone-h3-k27m-mutation-and-post-translational-modifications-in-pediatric-diffuse-midline-glioma-via-tissue-immunohistochemistry-informs-diagnosis-and-clinical-outcomes
#4
Tina Huang, Roxanna Garcia, Jin Qi, Rishi Lulla, Craig Horbinski, Amir Behdad, Nitin Wadhwani, Ali Shilatifard, Charles James, Amanda Saratsis
Pediatric diffuse midline glioma is a highly morbid glial neoplasm that may arise in the thalamus or brainstem (also known as diffuse intrinsic pontine glioma or DIPG). Because tumor anatomic location precludes surgical resection, diagnosis and treatment is based on MR imaging and analysis of biopsy specimens. Up to 80% of pediatric diffuse midline gliomas harbor a histone H3 mutation resulting in the replacement of lysine 27 with methionine (K27M) in genes encoding histone H3 variant H3.3 ( H3F3A ) or H3.1 ( HIST1H3B )...
December 14, 2018: Oncotarget
https://read.qxmd.com/read/30607770/diffuse-intrinsic-pontine-gliomas-exhibit-cell-biological-and-molecular-signatures-of-fetal-hindbrain-derived-neural-progenitor-cells
#5
Yu Sun, Cheng Xu, Changcun Pan, Xin Chen, Yibo Geng, Yuliang Wu, Peng Zhang, Wenhao Wu, Yu Wang, Deling Li, Zhen Wu, Junting Zhang, Qiaoran Xi, Liwei Zhang
Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG...
January 3, 2019: Neuroscience Bulletin
https://read.qxmd.com/read/30599251/safety-and-efficacy-of-endoscopic-third-ventriculostomy-in-diffuse-intrinsic-pontine-glioma-related-hydrocephalus-a-systematic-review
#6
REVIEW
Lelio Guida, Frank-Emmanuel Roux, Maura Massimino, Carlo E Marras, Erik Sganzerla, Carlo Giussani
OBJECT: Diffuse Intrinsic Pontine Gliomas (DIPG) related hydrocephalus occurs as the result of tumor growth and Aqueduct obstruction. There is no consensus about the best surgical option, thus a review has been performed to clarify the rate of success, complications and possible issues of Endoscopic Third Ventriculostomy (ETV) in comparison to the other available techniques. METHODS: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and it was registered with the PROSPERO International Prospective Register of Systematic Reviews(CRD42018089001)...
December 29, 2018: World Neurosurgery
https://read.qxmd.com/read/30595505/histone-h3-3-k27m-accelerates-spontaneous-brainstem-glioma-and-drives-restricted-changes-in-bivalent-gene-expression
#7
Jon D Larson, Lawryn H Kasper, Barbara S Paugh, Hongjian Jin, Gang Wu, Chang-Hyuk Kwon, Yiping Fan, Timothy I Shaw, André B Silveira, Chunxu Qu, Raymond Xu, Xiaoyan Zhu, Junyuan Zhang, Helen R Russell, Jennifer L Peters, David Finkelstein, Beisi Xu, Tong Lin, Christopher L Tinkle, Zoltan Patay, Arzu Onar-Thomas, Stanley B Pounds, Peter J McKinnon, David W Ellison, Jinghui Zhang, Suzanne J Baker
Diffuse intrinsic pontine gliomas (DIPGs) are incurable childhood brainstem tumors with frequent histone H3 K27M mutations and recurrent alterations in PDGFRA and TP53. We generated genetically engineered inducible mice and showed that H3.3 K27M enhanced neural stem cell self-renewal while preserving regional identity. Neonatal induction of H3.3 K27M cooperated with activating platelet-derived growth factor receptor α (PDGFRα) mutant and Trp53 loss to accelerate development of diffuse brainstem gliomas that recapitulated human DIPG gene expression signatures and showed global changes in H3K27 posttranslational modifications, but relatively restricted gene expression changes...
December 11, 2018: Cancer Cell
https://read.qxmd.com/read/30579270/clinical-tolerance-of-corticospinal-tracts-in-convection-enhanced-delivery-to-the-brainstem
#8
Peter F Morgenstern, Zhiping Zhou, Eva Wembacher-Schröder, Vincent Cina, Apostolos John Tsiouris, Mark M Souweidane
OBJECTIVEConvection-enhanced delivery (CED) has been explored as a therapeutic strategy for diffuse intrinsic pontine glioma (DIPG). Variables that may affect tolerance include infusate volume, infusion rate, catheter trajectory, and target position. Supratentorial approaches for catheter placement and infusate distribution patterns may conflict with corticospinal tracts (CSTs). The clinical relevance of these anatomical constraints has not been described. The authors report their experience using CED in the brainstem as it relates to anatomical CST conflict and association with clinical tolerance...
December 21, 2018: Journal of Neurosurgery
https://read.qxmd.com/read/30544335/phase-i-trial-of-convection-enhanced-delivery-of-il13-pseudomonas-toxin-in-children-with-diffuse-intrinsic-pontine-glioma
#9
John D Heiss, Aria Jamshidi, Smit Shah, Staci Martin, Pamela L Wolters, Davis P Argersinger, Katherine E Warren, Russell R Lonser
OBJECTIVEIn this clinical trial report, the authors analyze safety and infusion distribution of IL13-Pseudomonas exotoxin, an antitumor chimeric molecule, administered via intratumoral convection enhanced delivery (CED) in pediatric patients with diffuse intrinsic pontine glioma (DIPG).METHODSThis was a Phase I single-institution, open-label, dose-escalation, safety and tolerability study of IL13-PE38QQR infused via single-catheter CED into 5 pediatric DIPG patients. IL13-PE38QQR was administered to regions of tumor selected by radiographic findings...
December 1, 2018: Journal of Neurosurgery. Pediatrics
https://read.qxmd.com/read/30484948/ketogenic-diet-treatment-in-recurrent-diffuse-intrinsic-pontine-glioma-in-children-a-safety-and-feasibility-study
#10
Elles J T M van der Louw, Roel E Reddingius, Joanne F Olieman, Rinze F Neuteboom, Coriene E Catsman-Berrevoets
BACKGROUND: The mean overall survival rate of children with diffuse intrinsic pontine glioma (DIPG) is 9-11 months, with current standard treatment with fractionated radiotherapy and adjuvant chemotherapy. So far, novel therapeutic strategies have not yet resulted in significantly better survival. The main source of energy for glioblastoma cells is glucose. Therefore, metabolic alterations induced by the use of the extremely carbohydrate-restricted ketogenic diet (KD) as adjuvant therapy are subject of interest in cancer research...
November 28, 2018: Pediatric Blood & Cancer
https://read.qxmd.com/read/30460397/molecular-profiling-of-tumors-of-the-brainstem-by-sequencing-of-csf-derived-circulating-tumor-dna
#11
Changcun Pan, Bill H Diplas, Xin Chen, Yuliang Wu, Xiong Xiao, Liping Jiang, Yibo Geng, Cheng Xu, Yu Sun, Peng Zhang, Wenhao Wu, Yu Wang, Zhen Wu, Junting Zhang, Yuchen Jiao, Hai Yan, Liwei Zhang
Brainstem gliomas are molecularly heterogeneous diseases, many of which are difficult to safely surgically resect and have limited treatment options due to their eloquent location. These constraints pose challenges to biopsy, which limits the use of routine molecular profiling and identification of personalized therapies. Here, we explored the potential of sequencing of circulating tumor DNA (ctDNA) isolated from the cerebrospinal fluid (CSF) of brainstem glioma patients as a less invasive approach for tumor molecular profiling...
November 20, 2018: Acta Neuropathologica
https://read.qxmd.com/read/30453529/intersection-of-brain-development-and-paediatric-diffuse-midline-gliomas-potential-role-of-microenvironment-in-tumour-growth
#12
REVIEW
Katie F Loveson, Helen L Fillmore
Diffuse intrinsic pontine glioma (DIPG) is a devastating and incurable paediatric brain tumour with a median overall survival of 9 months. Until recently, DIPGs were treated similarly to adult gliomas, but due to the advancement in molecular and imaging technologies, our understanding of these tumours has increased dramatically. While extensive research is being undertaken to determine the function of the molecular aberrations in DIPG, there are significant gaps in understanding the biology and the influence of the tumour microenvironment on DIPG growth, specifically in regards to the developing pons...
November 16, 2018: Brain Sciences
https://read.qxmd.com/read/30446898/international-experience-in-the-development-of-patient-derived-xenograft-models-of-diffuse-intrinsic-pontine-glioma
#13
Maria Tsoli, Han Shen, Chelsea Mayoh, Laura Franshaw, Anahid Ehteda, Danielle Upton, Diana Carvalho, Maria Vinci, Michael H Meel, Dannis van Vuurden, Alexander Plessier, David Castel, Rachid Drissi, Michael Farrell, Jane Cryan, Darach Crimmins, John Caird, Jane Pears, Stephanie Francis, Louise E A Ludlow, Andrea Carai, Angela Mastronuzzi, Bing Liu, Jordan Hansford, Nick Gottardo, Tim Hassall, Maria Kirby, Maryam Fouladi, Cynthia Hawkins, Michelle Monje, Jacques Grill, Chris Jones, Esther Hulleman, David S Ziegler
PURPOSE: Diffuse intrinsic pontine glioma is the most aggressive form of high grade glioma in children with no effective therapies. There have been no improvements in survival in part due poor understanding of underlying biology, and lack of representative in vitro and in vivo models. Recently, it has been found feasible to use both biopsy and autopsy tumors to generate cultures and xenograft models. METHODS: To further model development, we evaluated the collective international experience from 8 collaborating centers to develop DIPG pre-clinical models from patient-derived autopsies and biopsies...
January 2019: Journal of Neuro-oncology
https://read.qxmd.com/read/30417211/nimotuzumab-containing-regimen-for-pediatric-diffuse-intrinsic-pontine-gliomas-a-retrospective-multicenter-study-and-review-of-the-literature
#14
Rejin Kebudi, Fatma Betul Cakir, Sema Buyukkapu Bay, Omer Gorgun, Pelin Altınok, Ayça Iribas, Fulya Yaman Agaoglu, Emin Darendeliler
PURPOSE: Nimotuzumab is an IgG1 antibody that targets epidermal growth factor receptor (EGFR). Overexpression of EGFR is detected in some pediatric brain tumors including diffuse intrinsic pontine gliomas (DIPG)s. METHODS: Since May 2010, nimotuzumab, combined with carboplatin or vinorelbine or Temozolomide (TMZ), was administered during progressive disease (PD) after the use of the institutional protocol consisting of radiotherapy (RT) + TMZ and adjuvant TMZ...
January 2019: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://read.qxmd.com/read/30405776/identification-of-novel-long-non-coding-rna-in-diffuse-intrinsic-pontine-gliomas-by-expression-profile-analysis
#15
Yuehui Liu, Haiping Liu, Dongwei Zhang
Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating types of pediatric cancer. Accumulating evidence suggests that the dysregulated expression of long non-coding (lnc)-RNAs is associated with various pathologies of the CNS. However, the expression patterns and prognostic roles of lncRNAs in DIPG have not yet been systematically determined. In the present study, lncRNA expression profiles were obtained from the Gene Expression Omnibus (GEO) database using the lncRNA-mining approach and a differential expression analysis for lncRNAs was performed between DIPG and low-grade brainstem glioma and DIPG and normal pediatric brainstem tissue...
November 2018: Oncology Letters
https://read.qxmd.com/read/30402543/multiple-modes-of-prc2-inhibition-elicit-global-chromatin-alterations-in-h3k27m-pediatric-glioma
#16
James M Stafford, Chul-Hwan Lee, Philipp Voigt, Nicolas Descostes, Ricardo Saldaña-Meyer, Jia-Ray Yu, Gary Leroy, Ozgur Oksuz, Jessica R Chapman, Fernando Suarez, Aram S Modrek, N Sumru Bayin, Dimitris G Placantonakis, Matthias A Karajannis, Matija Snuderl, Beatrix Ueberheide, Danny Reinberg
A methionine substitution at lysine-27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits polycomb repressive complex 2 (PRC2) in a dominant-negative fashion. Yet, the mechanisms for this inhibition and abnormal epigenomic landscape have not been resolved. Using quantitative proteomics, we discovered that robust PRC2 inhibition requires levels of H3K27M greatly exceeding those of PRC2, seen in DIPG. While PRC2 inhibition requires interaction with H3K27M, we found that this interaction on chromatin is transient, with PRC2 largely being released from H3K27M...
October 2018: Science Advances
https://read.qxmd.com/read/30396367/transcriptomic-and-epigenetic-profiling-of-diffuse-midline-gliomas-h3-k27m-mutant-discriminate-two-subgroups-based-on-the-type-of-histone-h3-mutated-and-not-supratentorial-or-infratentorial-location
#17
David Castel, Cathy Philippe, Thomas Kergrohen, Martin Sill, Jane Merlevede, Emilie Barret, Stéphanie Puget, Christian Sainte-Rose, Christof M Kramm, Chris Jones, Pascale Varlet, Stefan M Pfister, Jacques Grill, David T W Jones, Marie-Anne Debily
Diffuse midline glioma (DMG), H3 K27M-mutant, is a new entity in the updated WHO classification grouping together diffuse intrinsic pontine gliomas and infiltrating glial neoplasms of the midline harboring the same canonical mutation at the Lysine 27 of the histones H3 tail.Two hundred and fifteen patients younger than 18 years old with centrally-reviewed pediatric high-grade gliomas (pHGG) were included in this study. Comprehensive transcriptomic (n = 140) and methylation (n = 80) profiling was performed depending on the material available, in order to assess the biological uniqueness of this new entity compared to other midline and hemispheric pHGG...
November 5, 2018: Acta Neuropathologica Communications
https://read.qxmd.com/read/30367915/histone-deacetylase-inhibitor-panobinostat-potentiates-the-anti-cancer-effects-of-mesenchymal-stem-cell-based-strail-gene-therapy-against-malignant-glioma
#18
Seung Ah Choi, Chanhee Lee, Pil Ae Kwak, Chul-Kee Park, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Seung-Ki Kim
Human adipose tissue-derived mesenchymal stem cells expressing the secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (hAT-MSC.sTRAIL) have demonstrated therapeutic activity against various tumors in preclinical studies. However, the limited expression of TRAIL death receptors remains a challenge. We evaluated the therapeutic efficacy of panobinostat in enhancing the sensitivity of hAT-MSC.sTRAIL-mediated apoptosis in malignant glioma. Panobinostat effectively inhibited all malignant glioma cells (IC50 , 0...
February 1, 2019: Cancer Letters
https://read.qxmd.com/read/30340362/cutting-edge-therapeutic-insights-derived-from-molecular-biology-of-pediatric-high-grade-glioma-and-diffuse-intrinsic-pontine-glioma-dipg
#19
REVIEW
Cavan P Bailey, Mary Figueroa, Sana Mohiuddin, Wafik Zaky, Joya Chandra
Pediatric high-grade glioma (pHGG) and brainstem gliomas are some of the most challenging cancers to treat in children, with no effective therapies and 5-year survival at ~2% for diffuse intrinsic pontine glioma (DIPG) patients. The standard of care for pHGG as a whole remains surgery and radiation combined with chemotherapy, while radiation alone is standard treatment for DIPG. Unfortunately, these therapies lack specificity for malignant glioma cells and have few to no reliable biomarkers of efficacy. Recent discoveries have revealed that epigenetic disruption by highly conserved mutations in DNA-packaging histone proteins in pHGG, especially DIPG, contribute to the aggressive nature of these cancers...
October 18, 2018: Bioengineering
https://read.qxmd.com/read/30254491/combined-use-of-cdk4-6-and-mtor-inhibitors-induce-synergistic-growth-arrest-of-diffuse-intrinsic-pontine-glioma-cells-via-mutual-downregulation-of-mtorc1-activity
#20
Daniel J Asby, Clare L Killick-Cole, Lisa J Boulter, William Gb Singleton, Claire A Asby, Marcella J Wyatt, Neil U Barua, Alison S Bienemann, Steven S Gill
Background: Diffuse intrinsic pontine glioma (DIPG) is a lethal type of pediatric brain tumor that is resistant to conventional chemotherapies. Palbociclib is a putative novel DIPG treatment that restricts the proliferation of rapidly dividing cancer cells via selective inhibition of cyclin-dependent kinase (CDK) 4 and CDK6. However, implementing palbociclib as a monotherapy for DIPG is unfeasible, as CDK4/6 inhibitor resistance is commonplace and palbociclib does not readily cross the blood-brain barrier (BBB) or persist in the central nervous system...
2018: Cancer Management and Research
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