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https://www.readbyqxmd.com/read/30544362/impact-of-the-h3k27m-mutation-on-survival-in-pediatric-high-grade-glioma-a-systematic-review-and-meta-analysis
#1
REVIEW
(no author information available yet)
OBJECTIVEPediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma, present a prognostic challenge given their lethality and rarity. A substitution mutation of lysine for methionine at position 27 in histone H3 (H3K27M) has been shown to be highly specific to these tumors. Data are accumulating regarding the poor outcomes of patients with these tumors; however, the quantification of pooled outcomes has yet to be done, which could assist in prioritizing management. The aim of this study was to quantitatively pool data in the current literature on the H3K27M mutation as an independent prognostic factor in pHGG...
November 1, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/30544335/phase-i-trial-of-convection-enhanced-delivery-of-il13-pseudomonas-toxin-in-children-with-diffuse-intrinsic-pontine-glioma
#2
(no author information available yet)
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://www.readbyqxmd.com/read/30484948/ketogenic-diet-treatment-in-recurrent-diffuse-intrinsic-pontine-glioma-in-children-a-safety-and-feasibility-study
#3
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/30484110/correction-to-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, Dannielle Upton, Diana Carvalho, Maria Vinci, Michael H Meel, Dannis van Vuurden, Alexandre 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, Nicholas G Gottardo, Tim Hassall, Maria Kirby, Maryam Fouladi, Cynthia Hawkins, Michelle Monje, Jacques Grill, Chris Jones, Esther Hulleman, David S Ziegler
There are two errors and one omission in the original article. Author Gottardo's correct name is Nicholas G. Gottardo, author Hulleman's correct affiliation is no. 3 (VUMC, Amsterdam), and the Acknowledgements should include the following sentence: "We would like to thank Dr Angel Montero Carcaboso (Hospital Sant Joan de Deu, Barcelona, Spain) for generously supplying the HSJD-DIPG007 cells."
November 27, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/30460397/molecular-profiling-of-tumors-of-the-brainstem-by-sequencing-of-csf-derived-circulating-tumor-dna
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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/30389438/detection-of-h3k27-m-mutation-in-cases-of-brain-stem-subependymoma
#12
Kun Yao, Zejun Duan, Yin Wang, Mingshan Zhang, Tao Fan, Bin Wu, Xueling Qi
Subependymomas are rare, slow-growing, grade I glial tumors of the central nervous system (CNS). Recently, diffuse midline gliomas with mutations in the H3.1 or H3.3 genes at the position of amino acid 27, resulting in the replacement of lysine by methionine (K27 M), which were defined as the new grade IV entity. As H3K27M mutations have been reported in midline gliomas, gangliogliomas and pilocytic astrocytomas, whether they occur in midline subependymomas has been unclear. We were to determine whether any such mutations can be found in them and to analyze the prognostic relevance of any such mutations in subependymomas...
October 30, 2018: Human Pathology
https://www.readbyqxmd.com/read/30385005/re-irradiation-for-paediatric-tumours
#13
D S Tsang, N J Laperriere
Despite best available therapy, many children with cancer develop recurrence after multimodal treatment, including initial radiation therapy. Re-irradiation is defined as the use of a second course of radiation therapy with a retreatment volume that overlaps substantially with that of a previously delivered course of radiation therapy. Re-irradiation is an important part of salvage treatment for patients with recurrent ependymoma, diffuse intrinsic pontine glioma, medulloblastoma and germinoma. In patients with ependymoma, conventionally fractionated re-irradiation (1...
October 29, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
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
#14
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/30366780/glioneuronal-brainstem-tumor-it-s-all-in-the-eyes
#15
Emma Foster, Catriona McLean, Owen White
A previously well man presented with several months' history of neurological symptoms including diplopia and balance difficulties. Examination revealed fluctuating neurological deficits, fatigable weakness and slowed saccades. Extensive testing revealed mildly elevated cerebrospinal fluid protein, strongly positive single fiber electromyography and a dorsal pontine lesion at the floor of the 4th ventricle. An autoimmune process was felt to best account for the myasthenic presentation while the differential diagnoses for the brainstem lesion included glioma...
October 23, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/30365657/behavioural-changes-caused-by-diffuse-intrinsic-pontine-glioma
#16
Pedro Tadao Hamamoto Filho, Igor Barreira Magro, Marco Antonio Zanini
No abstract text is available yet for this article.
July 2018: Revista da Associação Médica Brasileira
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
#17
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/30318760/longitudinal-evaluation-of-tumor-microenvironment-in-rat-focal-brainstem-glioma-using-diffusion-and-perfusion-mri
#18
Kulam Najmudeen Magdoom, Francisco Delgado, Ana C Bohórquez, Alec C Brown, Paul R Carney, Carlos Rinaldi, Thomas H Mareci, James R Ewing, Malisa Sarntinoranont
BACKGROUND: Brainstem gliomas are aggressive and difficult to treat. Growth of these tumors may be characterized with MRI methods. PURPOSE: To visualize longitudinal changes in tumor volume, vascular leakiness, and tissue microstructure in an animal model of brainstem glioma. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Male Sprague-Dawley rats (n = 9) were imaged with 9L gliosarcoma cells infused into the pontine reticular formation of the brainstem...
October 14, 2018: Journal of Magnetic Resonance Imaging: JMRI
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
#19
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/30210988/fluorescein-guided-surgery-for-pediatric-brainstem-gliomas-preliminary-study-and-technical-notes
#20
Zhan Xue, Lu Kong, Chang-Cun Pan, Zhen Wu, Jun-Ting Zhang, Li-Wei Zhang
Introduction  Brainstem gliomas (BsG) account for 10 to 15% of pediatric brain tumors. Surgery is the preferred treatment for focal and exophytic lesions. Sodium fluorescein has been proven safe and effective in resection of malignant brain tumors. Objective  The objective was to o analyze the safety and effectiveness of this approach, to evaluate intraoperative fluorescein imaging, and to measure the safety of chosen dose for pediatric patients. Methods  Twelve cases were enrolled between March 2014 and September 2016 in Beijing Tiantan Hospital...
October 2018: Journal of Neurological Surgery. Part B, Skull Base
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