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Diffuse intrinsic pontine

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https://www.readbyqxmd.com/read/28547002/oncolytic-herpes-simplex-virus-inhibits-pediatric-brain-tumor-migration-and-invasion
#1
Julia V Cockle, Anke Brüning-Richardson, Karen J Scott, Jill Thompson, Timothy Kottke, Ewan Morrison, Azam Ismail, Angel M Carcaboso, Ailsa Rose, Peter Selby, Joe Conner, Susan Picton, Susan Short, Richard Vile, Alan Melcher, Elizabeth Ilett
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action: the inhibition of migration and invasion in pediatric brain tumors. We evaluated the effect of oncolytic herpes simplex virus 1716 (HSV1716) on the migration and invasion of pHGG and DIPG both in vitro using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays and in vivo using an orthotopic xenograft model of DIPG invasion...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28544128/a-pediatric-trial-of-radiation-cetuximab-followed-by-irinotecan-cetuximab-in-newly-diagnosed-diffuse-pontine-gliomas-and-high-grade-astrocytomas-a-pediatric-oncology-experimental-therapeutics-investigators-consortium-study
#2
Margaret E Macy, Mark W Kieran, Susan N Chi, Kenneth J Cohen, Tobey J MacDonald, Amy A Smith, Michael M Etzl, Michele C Kuei, Andrew M Donson, Lia Gore, Jennifer DiRenzo, Tanya M Trippett, Irina Ostrovnaya, Aru Narendran, Nicholas K Foreman, Ira J Dunkel
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. METHODS: Eligible patients of age 3-21 years had newly diagnosed DIPG or HGA...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28542253/repurposing-the-anti-epileptic-drug-sodium-valproate-as-an-adjuvant-treatment-for-diffuse-intrinsic-pontine-glioma
#3
Clare L Killick-Cole, William G B Singleton, Alison S Bienemann, Daniel J Asby, Marcella J Wyatt, Lisa J Boulter, Neil U Barua, Steven S Gill
Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28541486/lessons-learned-from-diffuse-intrinsic-pontine-glioma-how-a-terrible-disease-forced-us-to-think-better
#4
Mark W Kieran
No abstract text is available yet for this article.
May 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28529053/unusual-intra-parenchymal-pontomedullary-epidermoid-cyst-in-a-2-year-old-case-report-and-literature-review
#5
Anan Shtaya, Bassam Dabbous, Evgenia Fanou, Leslie Bridges, Samantha Hettige
BACKGROUND: Intrinsic brainstem epidermoid cysts are rare, benign, slow growing lesions. Their eloquence preclude complete excision, however subtotal resection will often result in prolonged or sometimes permanent relief of presenting symptoms and signs. We describe an unusual case and review the literature of this pathology in the paediatric population. CASE DESCRIPTION: We report an intra-axial pontine epidermoid cyst in a 2-year-old girl who presented with developmental delay, multiple cranial nerve palsies and pneumonia...
May 18, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#6
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28486100/using-epigenetic-reprogramming-to-treat-pediatric-brain-cancer
#7
Milan G Chheda, David H Gutmann
In this issue of Cancer Cell, Nagaraja et al. dissect the molecular mechanisms underlying therapeutic responses to transcriptional disruptors in the fatal pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). Moreover, they identify super-enhancers mediating these effects, highlighting how normal brain developmental programs can be hijacked in cancer.
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28455399/drug-blocks-synaptic-hijacking-in-gliomas
#8
(no author information available yet)
An enzyme called ADAM10 cleaves a protein found in synaptic membranes, creating a soluble factor that can fuel the growth of brain tumors. Blocking this enzyme shrinks tumors in xenograft models of pediatric glioblastoma and diffuse intrinsic pontine glioma, two brain cancers with few to no effective drug options, researchers reported at the American Academy of Neurology 2017 Annual Meeting.
April 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28455397/targeting-cdk7-or-brd4-blocks-diffuse-intrinsic-pontine-glioma-growth
#9
(no author information available yet)
Diffuse intrinsic pontine glioma (DIPG) is sensitive to transcriptional disruption via CDK7/BRD4 blockade.
April 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28450157/the-dual-mtor-kinase-inhibitor-tak228-inhibits-tumorigenicity-and-enhances-radiosensitization-in-diffuse-intrinsic-pontine-glioma
#10
Hiroaki Miyahara, Sridevi Yadavilli, Manabu Natsumeda, Jeffrey A Rubens, Louis Rodgers, Madhuri Kambhampati, Isabella C Taylor, Harpreet Kaur, Laura Asnaghi, Charles G Eberhart, Katherine E Warren, Javad Nazarian, Eric H Raabe
Diffuse intrinsic pontine glioma (DIPG) is an invasive and treatment-refractory pediatric brain tumor. Primary DIPG tumors harbor a number of mutations including alterations in PTEN, AKT, and PI3K and exhibit activation of mammalian Target of Rapamycin Complex 1 and 2 (mTORC1/2). mTORC1/2 regulate protein translation, cell growth, survival, invasion, and metabolism. Pharmacological inhibition of mTORC1 is minimally effective in DIPG. However, the activity of dual TORC kinase inhibitors has not been examined in this tumor type...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28434841/transcriptional-dependencies-in-diffuse-intrinsic-pontine-glioma
#11
Surya Nagaraja, Nicholas A Vitanza, Pamelyn J Woo, Kathryn R Taylor, Fang Liu, Lei Zhang, Meng Li, Wei Meng, Anitha Ponnuswami, Wenchao Sun, Jie Ma, Esther Hulleman, Tomek Swigut, Joanna Wysocka, Yujie Tang, Michelle Monje
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28428205/measurable-supratentorial-white-matter-volume-changes-in-patients-with-diffuse-intrinsic-pontine-glioma-treated-with-an-anti-vascular-endothelial-growth-factor-agent-steroids-and-radiation
#12
P Svolos, W E Reddick, A Edwards, A Sykes, Y Li, J O Glass, Z Patay
BACKGROUND AND PURPOSE: Assessing the response to treatment in infiltrative brain tumors by using lesion volume-based response criteria is challenging. We hypothesized that in such tumors, volume measurements alone may not accurately capture changes in actual tumor burden during treatment. We longitudinally evaluated volume changes in both normal-appearing supratentorial white matter and the brain stem lesions in patients treated for diffuse intrinsic pontine glioma to determine to what extent adjuvant systemic therapies may skew the accuracy of tumor response assessments based on volumetric analysis...
April 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28416018/detection-of-histone-h3-mutations-in-cerebrospinal-fluid-derived-tumor-dna-from-children-with-diffuse-midline-glioma
#13
Tina Y Huang, Andrea Piunti, Rishi R Lulla, Jin Qi, Craig M Horbinski, Tadanori Tomita, C David James, Ali Shilatifard, Amanda M Saratsis
Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are highly morbid glial neoplasms of the thalamus or brainstem that typically arise in young children and are not surgically resectable. These tumors are characterized by a high rate of histone H3 mutation, resulting in replacement of lysine 27 with methionine (K27M) in genes encoding H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B). Detection of these gain-of-function mutations has clinical utility, as they are associated with distinct tumor biology and clinical outcomes...
April 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28404981/characterization-of-the-transcriptional-and-metabolic-responses-of-pediatric-high-grade-gliomas-to-mtor-hif-1a-axis-inhibition
#14
Aurélia Nguyen, François Marie Moussallieh, Alan Mackay, A Ercument Cicek, Andres Coca, Marie Pierre Chenard, Noelle Weingertner, Benoit Lhermitte, Eric Letouzé, Eric Guérin, Erwan Pencreach, Sarah Jannier, Dominique Guenot, Izzie Jacques Namer, Chris Jones, Natacha Entz-Werlé
Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401062/genomic-insights-into-diffuse-intrinsic-pontine-glioma
#15
REVIEW
Danielle H Lapin, Maria Tsoli, David S Ziegler
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor with a peak incidence in middle childhood and a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of over 250 clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care. The traditional practice to not biopsy DIPG led to a scarcity in available tissue samples for laboratory analysis that till recently hindered therapeutic advances...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28388610/untangling-the-role-of-mutant-histone-h3-in-diffuse-intrinsic-pontine-glioma
#16
Caretha L Creasy
No abstract text is available yet for this article.
April 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28385794/mri-and-pet-noninvasive-tools-to-probe-diffuse-intrinsic-pontine-glioma-biology
#17
Elizabeth Gerstner
No abstract text is available yet for this article.
April 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28371920/diffuse-intrinsic-pontine-gliomas-current-management-and-new-biologic-insights-is-there-a-glimmer-of-hope
#18
Kenneth J Cohen, Nada Jabado, Jacques Grill
Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor...
March 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28362421/a-protocol-for-rapid-post-mortem-cell-culture-of-diffuse-intrinsic-pontine-glioma-dipg
#19
Grant L Lin, Michelle Monje
Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brainstem tumor that carries a universally fatal prognosis. Because surgical resection is not a viable treatment strategy and biopsy is not routinely performed, the availability of patient samples for research is limited. Consequently, efforts to study this disease have been challenged by a paucity of faithful disease models. To address this need, we describe here a protocol for the rapid processing of post-mortem autopsy tissue samples in order to generate durable patient-derived cell culture models that can be used in in vitro assays or in vivo orthotopic xenograft experiments...
March 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28360212/correlation-of-18-f-fdg-pet-and-mr-apparent-diffusion-coefficient-adc-histogram-metrics-with-survival-in-diffuse-intrinsic-pontine-glioma-a-report-from-the-pediatric-brain-tumor-consortium
#20
Katherine Zukotynski, Sridhar Vajapeyam, Frederic H Fahey, Mehmet Kocak, Douglas Brown, Kelsey Ricci, Arzu Onar-Thomas, Maryam Fouladi, Tina Young Poussaint
Rationale: To describe baseline (18)F-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline magnetic resonance (MR) apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS) and overall survival (OS). Methods: Baseline brain FDG-PET and MR scans were obtained in 33 children from Pediatric Brain Tumor Consortium (PBTC) clinical DIPG trials. FDG-PET, post-gadolinium (PG) and ADC images were registered to baseline fluid attenuation inversion recovery (FLAIR) images...
March 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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