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Diffuse intrinsic pontine glioma ( DIPG )

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https://www.readbyqxmd.com/read/30484948/ketogenic-diet-treatment-in-recurrent-diffuse-intrinsic-pontine-glioma-in-children-a-safety-and-feasibility-study
#1
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://www.readbyqxmd.com/read/30460397/molecular-profiling-of-tumors-of-the-brainstem-by-sequencing-of-csf-derived-circulating-tumor-dna
#2
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://www.readbyqxmd.com/read/30453529/intersection-of-brain-development-and-paediatric-diffuse-midline-gliomas-potential-role-of-microenvironment-in-tumour-growth
#3
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://www.readbyqxmd.com/read/30446898/international-experience-in-the-development-of-patient-derived-xenograft-models-of-diffuse-intrinsic-pontine-glioma
#4
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...
November 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/30417211/nimotuzumab-containing-regimen-for-pediatric-diffuse-intrinsic-pontine-gliomas-a-retrospective-multicenter-study-and-review-of-the-literature
#5
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...
November 11, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/30405776/identification-of-novel-long-non-coding-rna-in-diffuse-intrinsic-pontine-gliomas-by-expression-profile-analysis
#6
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://www.readbyqxmd.com/read/30402543/multiple-modes-of-prc2-inhibition-elicit-global-chromatin-alterations-in-h3k27m-pediatric-glioma
#7
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://www.readbyqxmd.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
#8
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://www.readbyqxmd.com/read/30367915/histone-deacetylase-inhibitor-panobinostat-potentiates-the-anti-cancer-effects-of-mesenchymal-stem-cell-based-strail-gene-therapy-against-malignant-glioma
#9
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...
October 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/30340362/cutting-edge-therapeutic-insights-derived-from-molecular-biology-of-pediatric-high-grade-glioma-and-diffuse-intrinsic-pontine-glioma-dipg
#10
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://www.readbyqxmd.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
#11
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
https://www.readbyqxmd.com/read/30192215/tumor-dissemination-through-surgical-tracts-in-diffuse-intrinsic-pontine-glioma
#12
Maria-Jesus Lobon-Iglesias, Vicente Santa-Maria Lopez, Patricia Puerta Roldan, Santiago Candela-Cantó, Monica Ramos-Albiac, Marta Gomez-Chiari, Stephanie Puget, Stephanie Bolle, Liliana Goumnerova, Mark W Kieran, Ofelia Cruz, Jacques Grill, Andres Morales La Madrid
OBJECTIVE Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive and lethal brainstem tumor in children. In the 1980s, routine biopsy at presentation was abandoned since it was claimed "unnecessary" for diagnosis. In the last decade, however, several groups have reincorporated this procedure as standard of care or in the context of clinical trials. Expert neurosurgical teams report no mortality and acceptable morbidity, and no relevant complications have been previously described. The aim of this study was to review needle tract dissemination as a potential complication in DIPG...
September 7, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/30174560/measuring-tumor-metabolism-in-pediatric-diffuse-intrinsic-pontine-glioma-using-hyperpolarized-carbon-13-mr-metabolic-imaging
#13
Adam W Autry, Rintaro Hashizume, C David James, Peder E Z Larson, Daniel B Vigneron, Ilwoo Park
Objective: The purpose of this study was to demonstrate the feasibility of using hyperpolarized carbon-13 (13 C) metabolic imaging with [1-13 C]-labeled pyruvate for evaluating real-time in vivo metabolism of orthotopic diffuse intrinsic pontine glioma (DIPG) xenografts. Materials and Methods: 3D 13 C magnetic resonance spectroscopic imaging (MRSI) data were acquired on a 3T scanner from 8 rats that had been implanted with human-derived DIPG cells in the brainstem and 5 healthy controls, following injection of 2...
2018: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/30169876/characterization-of-the-immune-microenvironment-of-diffuse-intrinsic-pontine-glioma-implications-for-development-of-immunotherapy
#14
Nicole A P Lieberman, Kole DeGolier, Heather M Kovar, Amira Davis, Virginia Hoglund, Jeffrey Stevens, Conrad Winter, Gail Deutsch, Scott N Furlan, Nicholas A Vitanza, Sarah E S Leary, Courtney A Crane
Background: Diffuse Intrinsic Pontine Glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG tumors cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically, however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor expression in pediatric low- and high-grade gliomas and DIPG...
August 28, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/30138731/population-based-study-determining-predictors-of-cancer-specific-mortality-and-survival-in-pediatric-high-grade-brainstem-glioma
#15
Russell Maxwell, Andrew S Luksik, Tomas Garzon-Muvdi, Wuyang Yang, Judy Huang, Chetan Bettegowda, George I Jallo, Stephanie A Terezakis, Mari L Groves
BACKGROUND: Pediatric high-grade brainstem gliomas are aggressive tumors with dismal prognoses. Large-scale studies are needed to further characterize these tumors and determine factors influencing cancer-specific mortality and survival at varying time points. METHODS: We used the SEER (Surveillance Epidemiology and End Results) database to conduct a population-based study of pediatric patients with histologically confirmed anaplastic astrocytoma or glioblastoma tumors located within the brainstem...
November 2018: World Neurosurgery
https://www.readbyqxmd.com/read/30124166/bioinformatics-analysis-of-microarray-data-to-reveal-the-pathogenesis-of-diffuse-intrinsic-pontine-glioma
#16
Li Wei, Fei He, Wen Zhang, Wenhua Chen, Bo Yu
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. METHODS: 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. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool...
August 20, 2018: Biological Research
https://www.readbyqxmd.com/read/30101054/histone-h3-mutations-in-cancer
#17
REVIEW
Yi Ching Esther Wan, Jiaxian Liu, Kui Ming Chan
Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in chromatin-modifying enzymes has long been implicated in cancers. More recently, recurrent histone mutations have been identified in multiple cancers and have been shown to impede histone methylation. All three histone mutations (H3K27M, H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a lysine residue that is a target of methylation...
2018: Current Pharmacology Reports
https://www.readbyqxmd.com/read/30072503/evaluation-of-11-c-methionine-pet-and-anatomic-mri-associations-in-diffuse-intrinsic-pontine-glioma
#18
Christopher Tinkle, Elizabeth Duncan, Mikhail Doubrovin, Yuanyuan Han, Yimei Li, Hyun Kim, Alberto Broniscer, Scott E Snyder, Thomas E Merchant, Barry L Shulkin
The role of metabolic imaging in the diagnosis, treatment, and response assessment of diffuse intrinsic pontine glioma (DIPG) is poorly-defined. We investigated the uptake of 11 C-methionine (11 C-MET) in pediatric patients with newly diagnosed DIPG and evaluated the associations of 11 C-MET positron emission tomography (PET) metrics with conventional MRI indices and survival outcomes. Methods: Twenty-two patients with newly diagnosed DIPG were prospectively enrolled on an IRB-approved investigational study of 11 C-MET-PET...
August 2, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/30061363/melk-inhibition-in-diffuse-intrinsic-pontine-glioma
#19
Michaël H Meel, Mark C de Gooijer, Miriam Guillén Navarro, Piotr Waranecki, Marjolein Breur, Levi C M Buil, Laurine E Wedekind, Jos W R Twisk, Jan Koster, Rintaro Hashizume, Eric H Raabe, Angel Montero Carcaboso, Marianna Bugiani, Olaf van Tellingen, Dannis G van Vuurden, Gertjan J L Kaspers, Esther Hulleman
Purpose: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor, for which no effective therapeutic options currently exist. We here determined the potential of inhibition of the maternal embryonic leucine zipper kinase (MELK) for the treatment of DIPG. Experimental Design: We evaluated the antitumor efficacy of the small-molecule MELK inhibitor OTSSP167 in vitro in patient-derived DIPG cultures, and identified the mechanism of action of MELK inhibition in DIPG by RNA sequencing of treated cells...
July 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30049282/medulloblastoma-therapy-generates-risk-of-a-poorly-prognostic-h3-wild-type-subgroup-of-diffuse-intrinsic-pontine-glioma-a-report-from-the-international-dipg-registry
#20
Hunter C Gits, Maia Anderson, Stefanie Stallard, Drew Pratt, Becky Zon, Christopher Howell, Chandan Kumar-Sinha, Pankaj Vats, Katayoon Kasaian, Daniel Polan, Martha Matuszak, Daniel E Spratt, Marcia Leonard, Tingting Qin, Lili Zhao, James Leach, Brooklyn Chaney, Nancy Yanez Escorza, Jacob Hendershot, Blaise Jones, Christine Fuller, Sarah Leary, Ute Bartels, Eric Bouffet, Torunn I Yock, Patricia Robertson, Rajen Mody, Sriram Venneti, Arul M Chinnaiyan, Maryam Fouladi, Nicholas G Gottardo, Carl Koschmann
With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years)...
July 26, 2018: Acta Neuropathologica Communications
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