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https://www.readbyqxmd.com/read/28416018/detection-of-histone-h3-mutations-in-cerebrospinal-fluid-derived-tumor-dna-from-children-with-diffuse-midline-glioma
#1
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/28401062/genomic-insights-into-diffuse-intrinsic-pontine-glioma
#2
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/28373034/topical-delivery-of-anthramycin-i-influence-of-neat-solvents
#3
Tasnuva Haque, Khondaker M Rahman, David E Thurston, Jonathan Hadgraft, Majella E Lane
Anthramycin (ANT) was the first pyrrolobenzodiazepine (PBD) molecule to be isolated, and is a potent cytotoxic agent. Although the PBD family has been investigated for use in systemic chemotherapy, their application in the management of actinic keratoses (AK) or skin cancer has not been investigated to date. In the present work, anthramycin (ANT) was selected as a model PBD compound, and the skin penetration of the molecule was investigated using conventional Franz diffusion cells. Finite dose permeation studies of ANT were performed using propylene glycol (PG), 1,3-butanediol (BD), dipropylene glycol (DiPG), Transcutol P® (TC), propylene glycol monocaprylate (PGMC), propylene glycol monolaurate (PGML) and isopropyl myristate (IPM)...
March 31, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28371920/diffuse-intrinsic-pontine-gliomas-current-management-and-new-biologic-insights-is-there-a-glimmer-of-hope
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28339768/the-transcription-factor-olig2-is-important-for-the-biology-of-diffuse-intrinsic-pontine-gliomas
#7
Jane L Anderson, Ranjithmenon Muraleedharan, Nicole Oatman, Amanda Klotter, Satarupa Sengupta, Ronald R Waclaw, Jianqiang Wu, Rachid Drissi, Lili Miles, Eric H Raabe, Matthew L Weirauch, Maryam Fouladi, Lionel M Chow, Lindsey Hoffman, Mariko DeWire, Biplab Dasgupta
Background.: Diffuse intrinsic pontine glioma (DIPG) is a high-grade brainstem glioma of children with dismal prognosis. There is no single unifying model about the cell of origin of DIPGs. Proliferating cells in the developing human and mouse pons, the site of DIPGs, express neural stem/progenitor cell (NPC) markers, including Sox2, nestin, vimentin, Olig2, and glial fibrillary acidic protein, in an overlapping and non-overlapping manner, suggesting progenitor cell heterogeneity in the pons...
February 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28291423/preclinical-evaluation-of-convection-enhanced-delivery-of-liposomal-doxorubicin-to-treat-pediatric-diffuse-intrinsic-pontine-glioma-and-thalamic-high-grade-glioma
#8
A Charlotte P Sewing, Tonny Lagerweij, Dannis G van Vuurden, Michaël H Meel, Susanna J E Veringa, Angel M Carcaboso, Pieter J Gaillard, W Peter Vandertop, Pieter Wesseling, David Noske, Gertjan J L Kaspers, Esther Hulleman
OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models...
February 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28283507/inhibition-of-ezh2-or-bet-suppresses-diffuse-intrinsic-pontine-glioma
#9
(no author information available yet)
H3K27M-expressing diffuse intrinsic pontine gliomas (DIPG) are dependent on residual PRC2 activity.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28274399/radiation-and-subsequent-reirradiation-outcomes-in-the-treatment-of-diffuse-intrinsic-pontine-glioma-and-a-systematic-review-of-the-reirradiation-literature
#10
REVIEW
Christopher Freese, Vinita Takiar, Maryam Fouladi, Mariko DeWire, John Breneman, Luke Pater
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric disease, with a median survival of <1 year. Here, we review our institution's DIPG experience over an 8-year interval and perform a systematic review of the literature, specifically evaluating reports of reirradiation (reRT) for DIPG. METHODS AND MATERIALS: We retrospectively reviewed the medical records of 26 patients who underwent definitive intensity modulated radiation therapy (IMRT) for DIPG at a single institution between 2007 and 2015...
March 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28263309/ezh2-is-a-potential-therapeutic-target-for-h3k27m-mutant-pediatric-gliomas
#11
Faizaan Mohammad, Simon Weissmann, Benjamin Leblanc, Deo P Pandey, Jonas W Højfeldt, Itys Comet, Chunqin Zheng, Jens Vilstrup Johansen, Nicolas Rapin, Bo T Porse, Andrey Tvardovskiy, Ole N Jensen, Nagore G Olaciregui, Cinzia Lavarino, Mariona Suñol, Carmen de Torres, Jaume Mora, Angel M Carcaboso, Kristian Helin
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that is located in the pons and primarily affects children. Nearly 80% of DIPGs harbor mutations in histone H3 genes, wherein lysine 27 is substituted with methionine (H3K27M). H3K27M has been shown to inhibit polycomb repressive complex 2 (PRC2), a multiprotein complex responsible for the methylation of H3 at lysine 27 (H3K27me), by binding to its catalytic subunit EZH2. Although DIPGs with the H3K27M mutation show global loss of H3K27me3, several genes retain H3K27me3...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28263307/therapeutic-targeting-of-polycomb-and-bet-bromodomain-proteins-in-diffuse-intrinsic-pontine-gliomas
#12
Andrea Piunti, Rintaro Hashizume, Marc A Morgan, Elizabeth T Bartom, Craig M Horbinski, Stacy A Marshall, Emily J Rendleman, Quanhong Ma, Yoh-Hei Takahashi, Ashley R Woodfin, Alexander V Misharin, Nebiyu A Abshiru, Rishi R Lulla, Amanda M Saratsis, Neil L Kelleher, C David James, Ali Shilatifard
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor characterized by rapid and uniform patient demise. A heterozygous point mutation of histone H3 occurs in more than 80% of these tumors and results in a lysine-to-methionine substitution (H3K27M). Expression of this histone mutant is accompanied by a reduction in the levels of polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation (H3K27me3), and this is hypothesized to be a driving event of DIPG oncogenesis...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28254596/robot-assisted-stereotactic-biopsy-of-diffuse-intrinsic-pontine-glioma-a-single-centre-experience
#13
Andrea Carai, Angela Mastronuzzi, Alessandro De Benedictis, Raffaella Messina, Antonella Cacchione, Evelina Miele, Franco Randi, Giacomo Esposito, Andrea Trezza, Giovanna Stefania Colafati, Alessandra Savioli, Franco Locatelli, Carlo Efisio Marras
BACKGROUND: Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood tumor with dismal prognosis. Emerging molecular signatures have paved the way for stereotactic biopsy in selected Centers. We present our experience in DIPG stereotactic needle biopsy using the Robotic Stereotactic Assisted system (ROSA™) in a consecutive pediatric series. METHODS: All stereotactic biopsy procedures for DIPG performed during the last year at our Institution were considered. All procedures were carried out using the ROSA™ surgical assistant through a precoronary approach...
February 27, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28251325/second-re-irradiation-for-dipg-progression-re-considering-old-strategies-with-new-approaches
#14
Andres Morales La Madrid, Vicente Santa-María, Ofelia Cruz Martinez, Jaume Mora, Patricia Puerta Roldan, Antonio Guillen Quesada, Mariona Suñol Capella, Carmen de Torres Gomez-Pallete, Alvaro Lassaletta, Normand Laperriere, Salvador Villà, Eric Bouffet
Diffuse intrinsic pontine glioma (DIPG) is an aggressive infiltrative glioma for which no curative therapy is available. Radiation therapy (RT) is the only potentially effective intervention in delaying tumor progression, but only transiently. At progression, re-irradiation is gaining popularity as an effective palliative therapy. However, at second progression, exclusive symptomatic treatment is usually offered. Here we report two patients with DIPG at second progression who were treated with a second re-irradiation course with good response...
March 1, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28236065/glioblastoma-spheroids-produce-infiltrative-gliomas-in-the-rat-brainstem
#15
Zhiping Zhou, Neal Luther, Ranjodh Singh, John A Boockvar, Mark M Souweidane, Jeffrey P Greenfield
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is universally fatal without proven therapy other than radiation therapy for palliation. Representative animal models will play an essential role in the preclinical stage of future therapy development. To address the shortage of representative models, we created a novel infiltrative brainstem glioma model in rats based on glioblastoma spheroids. METHODS: Cells dissociated from glioblastoma spheroids grown from surgical specimens were implanted into the brainstem of NIH nude rats...
March 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28178670/new-in-vivo-avatars-of-diffuse-intrinsic-pontine-gliomas-dipg-from-stereotactic-biopsies-performed-at-diagnosis
#16
Alexandre Plessier, Ludivine Le Dret, Pascale Varlet, Kévin Beccaria, Joëlle Lacombe, Sébastien Mériaux, Françoise Geffroy, Laurence Fiette, Patricia Flamant, Fabrice Chrétien, Thomas Blauwblomme, Stéphanie Puget, Jacques Grill, Marie-Anne Debily, David Castel
Diffuse Instrinsic Pontine Glioma is the most aggressive form of High Grade Gliomas in children. The lack of biological material and the absence of relevant models have hampered the development of new therapeutics. Their extensive infiltration of the brainstem renders any surgical resection impossible and until recently biopsies were considered not informative enough and therefore not recommended. Thus, most models were derived from autopsy material. We aimed to develop relevant in vivo DIPG models that mimic this specific disease and its molecular diversity from tumor material obtained at diagnosis...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28161497/survival-benefit-for-patients-with-diffuse-intrinsic-pontine-glioma-dipg-undergoing-re-irradiation-at-first-progression-a-matched-cohort-analysis-on-behalf-of-the-siop-e-hgg-dipg-working-group
#17
Geert O Janssens, Lorenza Gandola, Stephanie Bolle, Henry Mandeville, Monica Ramos-Albiac, Karen van Beek, Helen Benghiat, Bianca Hoeben, Andres Morales La Madrid, Rolf-Dieter Kortmann, Darren Hargrave, Johan Menten, Emilia Pecori, Veronica Biassoni, Andre O von Bueren, Dannis G van Vuurden, Maura Massimino, Dominik Sturm, Max Peters, Christof M Kramm
BACKGROUND: Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression. METHODS: At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28120771/diffuse-intrinsic-pontine-gliomas-in-children-interest-of-robotic-frameless-assisted-biopsy-a-technical-note
#18
H A Coca, H Cebula, M Benmekhbi, M P Chenard, N Entz-Werle, F Proust
INTRODUCTION: Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all brain tumors in the pediatric population; currently prognosis remains poor, with an overall survival of 7-14 months. Recently the indication of DIPG biopsy has been enlarged due to the development of molecular biology and various ongoing clinical and therapeutic trials. Classically a biopsy is performed using a stereotactic frame assisted procedure but the workflow may sometimes be heavy and more complex especially in children...
December 2016: Neuro-Chirurgie
https://www.readbyqxmd.com/read/28110411/development-of-the-siope-dipg-network-registry-and-imaging-repository-a-collaborative-effort-to-optimize-research-into-a-rare-and-lethal-disease
#19
Sophie E M Veldhuijzen van Zanten, Joshua Baugh, Brooklyn Chaney, Dennis De Jongh, Esther Sanchez Aliaga, Frederik Barkhof, Johan Noltes, Ruben De Wolf, Jet Van Dijk, Antonio Cannarozzo, Carin M Damen-Korbijn, Jan A Lieverst, Niclas Colditz, Marion Hoffmann, Monika Warmuth-Metz, Brigitte Bison, David T W Jones, Dominik Sturm, Gerrit H Gielen, Chris Jones, Esther Hulleman, Raphael Calmon, David Castel, Pascale Varlet, Géraldine Giraud, Irene Slavc, Stefaan Van Gool, Sandra Jacobs, Filip Jadrijevic-Cvrlje, David Sumerauer, Karsten Nysom, Virve Pentikainen, Sanna-Maria Kivivuori, Pierre Leblond, Natasha Entz-Werle, Andre O von Bueren, Antonis Kattamis, Darren R Hargrave, Péter Hauser, Miklos Garami, Halldora K Thorarinsdottir, Jane Pears, Lorenza Gandola, Giedre Rutkauskiene, Geert O Janssens, Ingrid K Torsvik, Marta Perek-Polnik, Maria J Gil-da-Costa, Olga Zheludkova, Liudmila Shats, Ladislav Deak, Lidija Kitanovski, Ofelia Cruz, Andres Morales La Madrid, Stefan Holm, Nicolas Gerber, Rejin Kebudi, Richard Grundy, Enrique Lopez-Aguilar, Marta Zapata-Tarres, John Emmerik, Tim Hayden, Simon Bailey, Veronica Biassoni, Maura Massimino, Jacques Grill, William P Vandertop, Gertjan J L Kaspers, Maryam Fouladi, Christof M Kramm, Dannis G van Vuurden
Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network...
April 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28108511/biomarker-based-pet-imaging-of-diffuse-intrinsic-pontine-glioma-in-mouse-models
#20
Susanne Kossatz, Brandon Carney, Melanie Schweitzer, Giuseppe Carlucci, Vesselin Z Miloushev, Uday B Maachani, Prajwal Rajappa, Kayvan R Keshari, David Pisapia, Wolfgang A Weber, Mark M Souweidane, Thomas Reiner
Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize a positron emission tomography (PET) probe for imaging DIPG in vivo In human histological tissues, the probes target, PARP1, was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model, and probe uptake correlated to histologically determined tumor infiltration. Imaging with the sister fluorescence agent revealed that uptake was confined to proliferating, PARP1-expressing cells...
April 15, 2017: Cancer Research
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