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Diffuse Intrinsic Pontine Glioma

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https://www.readbyqxmd.com/read/28821206/contemporary-survival-endpoints-an-international-diffuse-intrinsic-pontine-glioma-registry-study
#1
Tabitha Cooney, Adam Lane, Ute Bartels, Eric Bouffet, Stewart Goldman, Sarah E S Leary, Nicholas K Foreman, Roger J Packer, Alberto Broniscer, Jane E Minturn, Chie-Schin Shih, Murali Chintagumpala, Tim Hassall, Nicholas G Gottardo, Hetal Dholaria, Lindsey Hoffman, Brooklyn Chaney, Joshua Baugh, Renee Doughman, James L Leach, Blaise V Jones, Maryam Fouladi, Katherine E Warren, Michelle Monje
No abstract text is available yet for this article.
September 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28818988/multiregional-tumor-drug-uptake-imaging-by-pet-and-microvascular-morphology-in-end-stage-diffuse-intrinsic-pontine-glioma
#2
Sophie E M Veldhuijzen van Zanten, A Charlotte P Sewing, Arthur van Lingen, Otto S Hoekstra, Pieter Wesseling, Michaël H Meel, Dannis G van Vuurden, Gertjan J L Kaspers, Esther Hulleman, Marianna Bugiani
Inadequate tumor uptake of the vascular endothelial growth factor (VEGF) antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma (DIPG). Methods: By combining data from a positron emission tomography (PET) imaging study using zirconium-89((89)Zr)-labeled bevacizumab and an autopsy study, a 1-on-1 analysis of multiregional in vivo and ex vivo (89)Zr-bevacizumab uptake, tumor histology and vascular morphology in a DIPG patient was performed. Results: In vivo (89)Zr-bevacizumab measurements showed heterogeneity between lesions...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28792659/molecular-alterations-in-pediatric-brainstem-gliomas
#3
Mikaela Porkholm, Anna Raunio, Reetta Vainionpää, Tarja Salonen, Juha Hernesniemi, Leena Valanne, Jarno Satopää, Atte Karppinen, Minna Oinas, Olli Tynninen, Virve Pentikäinen, Sanna-Maria Kivivuori
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group...
August 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28790919/potential-new-therapies-for-pediatric-diffuse-intrinsic-pontine-glioma
#4
REVIEW
Wenyong Long, Yang Yi, Shen Chen, Qi Cao, Wei Zhao, Qing Liu
Diffuse intrinsic pontine glioma (DIPG) is an extensively invasive malignancy with infiltration into other regions of the brainstem. Although large numbers of specific targeted therapies have been tested, no significant progress has been made in treating these high-grade gliomas. Therefore, the identification of new therapeutic approaches is of great importance for the development of more effective treatments. This article reviews the conventional therapies and new potential therapeutic approaches for DIPG, including epigenetic therapy, immunotherapy, and the combination of stem cells with nanoparticle delivery systems...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28780023/shared-acvr1-mutations-in-fop-and-dipg-opportunities-and-challenges-in-extending-biological-and-clinical-implications-across-rare-diseases
#5
Harry J Han, Payal Jain, Adam C Resnick
Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation...
August 2, 2017: Bone
https://www.readbyqxmd.com/read/28775236/patient-derived-dipg-cells-preserve-stem-like-characteristics-and-generate-orthotopic-tumors
#6
Cheng Xu, Xiaoqing Liu, Yibo Geng, Qingran Bai, Changcun Pan, Yu Sun, Xin Chen, Hai Yu, Yuliang Wu, Peng Zhang, Wenhao Wu, Yu Wang, Zhen Wu, Juntin Zhang, Zhaohui Wang, Rui Yang, Jenna Lewis, Darell Bigner, Fangping Zhao, Yiping He, Hai Yan, Qin Shen, Liwei Zhang
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor, with a median survival of less than one year. Due to enormous difficulties in the acquisition of DIPG specimens and the sophisticated technique required to perform brainstem orthotopic injection, only a handful of DIPG pre-clinical models are available. In this study, we successfully established eight patient-derived DIPG cell lines, mostly derived from treatment-naïve surgery or biopsy specimens. These patient-derived cell lines can be stably passaged in serum-free neural stem cell media and displayed distinct morphologies, growth rates and chromosome abnormalities...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28748343/a-phase-i-ii-study-of-gemcitabine-during-radiotherapy-in-children-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#7
Sophie E M Veldhuijzen van Zanten, Fatma E El-Khouly, Marc H A Jansen, Dewi P Bakker, Esther Sanchez Aliaga, Cornelis J A Haasbeek, Nicole I Wolf, C Michel Zwaan, W Peter Vandertop, Dannis G van Vuurden, Gertjan J L Kaspers
The purpose of this phase I/II, open-label, single-arm trial is to investigate the safety, tolerability, maximum tolerated dose and preliminary efficacy of the potential radiosensitizer gemcitabine, administered concomitantly to radiotherapy, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Six doses of weekly gemcitabine were administered intravenously, concomitantly to 6 weeks of hyperfractionated radiotherapy. Successive cohorts received increasing doses of 140, 175 and 200 mg/m(2) gemcitabine, respectively, following a 3 + 3 dose-escalation schedule without expansion cohort...
July 26, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28686124/influence-of-an-intratumoral-cyst-on-drug-distribution-by-convection-enhanced-delivery-case-report
#8
Iryna Ivasyk, Peter F Morgenstern, Eva Wembacher-Schroeder, Mark M Souweidane
Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. The patient was treated according to protocol with CED of (124)I-8H9 to the pons for nonprogressive DIPG after radiation therapy as part of a Phase I trial (clinical trial registration no...
July 7, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28662135/preliminary-dosimetric-study-on-feasibility-of-multi-beam-boron-neutron-capture-therapy-in-patients-with-diffuse-intrinsic-pontine-glioma-without-craniotomy
#9
Jia-Cheng Lee, Keh-Shih Chuang, Yi-Wei Chen, Fang-Yuh Hsu, Fong-In Chou, Sang-Hue Yen, Yuan-Hung Wu
Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT...
2017: PloS One
https://www.readbyqxmd.com/read/28643992/recent-perspectives-of-molecular-aberrations-in-pediatric-high-grade-glioma
#10
Zhengwei Li, Qingzeng Sun, Yingchun Shi
Paediatric high-grade glioma (HGG), including diffuse intrinsic pontine glioma (DIPG) are highly aggressive tumours with no effective cures. Lack of understanding of the molecular biology of these tumours, in part due to lack of well-characterized pre-clinical models, is a great challenge in the development of novel therapies. Recent studies have shown that paediatric HGG short-term cell cultures retain many of the tumour characteristics in vivo and at present one of the best choices for in-vivo experimental studies...
June 22, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28621573/update-on-the-diagnostic-value-and-safety-of-stereotactic-biopsy-for-pediatric-brainstem-tumors-a-systematic-review-and-meta-analysis-of-735-cases
#11
Christina Hamisch, Philipp Kickingereder, Matthias Fischer, Thorsten Simon, Maximilian I Ruge
OBJECTIVE Recent studies have shed light on the molecular makeup of diffuse intrinsic pontine gliomas and led to the identification of potential treatment targets for these lesions, which account for the majority of pediatric brainstem tumors (pedBSTs). Therefore, stereotactic biopsy-driven molecular characterization of pedBSTs may become an important prerequisite for the management of these fatal brain tumors. The authors conducted a systemic review and meta-analysis to precisely determine the safety and diagnostic success of stereotactic biopsy of pedBSTs...
June 16, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28592748/epigenetic-targeted-therapy-for-diffuse-intrinsic-pontine-glioma
#12
Rintaro Hashizume
Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5-7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone...
June 7, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28591729/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#13
Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B Stevenson, Maryam Fouladi, Rachid Drissi
Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587626/evaluation-of-a-novel-antibody-to-define-histone-3-3-g34r-mutant-brain-tumours
#14
Farhana Haque, Pascale Varlet, Julien Puntonet, Lisa Storer, Aikaterini Bountali, Ruman Rahman, Jacques Grill, Angel M Carcaboso, Chris Jones, Robert Layfield, Richard G Grundy
Missense somatic mutations affecting histone H3.1 and H3.3 proteins are now accepted as the hallmark of paediatric diffuse intrinsic pontine gliomas (DIPG), non-brain stem paediatric high grade gliomas (pHGG) as well as a subset of adult glioblastoma multiforme (GBM). Different mutations give rise to one of three amino acid substitutions at two critical positions within the histone tails, K27M, G34R/V. Several studies have highlighted gene expression and epigenetic changes associated with histone H3 mutations; however their precise roles in tumourigenesis remain incompletely understood...
June 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28566437/local-dna-repair-inhibition-for-sustained-radiosensitization-of-high-grade-gliomas
#15
Amanda R King, Christopher D Corso, Evan M Chen, Eric Song, Paul Bongiorni, Zhe Chen, Ranjini K Sundaram, Ranjit S Bindra, W Mark Saltzman
High-grade gliomas, such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), are characterized by an aggressive phenotype with nearly universal local disease progression despite multimodal treatment, which typically includes chemotherapy, radiotherapy, and possibly surgery. Radiosensitizers that have improved the effects of radiotherapy for extracranial tumors have been ineffective for the treatment of GBM and DIPG, in part due to poor blood-brain barrier penetration and rapid intracranial clearance of small molecules...
August 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28560664/external-validation-of-the-diffuse-intrinsic-pontine-glioma-survival-prediction-model-a-collaborative-report-from-the-international-dipg-registry-and-the-siope-dipg-registry
#16
Sophie E M Veldhuijzen van Zanten, Adam Lane, Martijn W Heymans, Joshua Baugh, Brooklyn Chaney, Lindsey M Hoffman, Renee Doughman, Marc H A Jansen, Esther Sanchez, William P Vandertop, Gertjan J L Kaspers, Dannis G van Vuurden, Maryam Fouladi, Blaise V Jones, James Leach
We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities...
August 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28547002/oncolytic-herpes-simplex-virus-inhibits-pediatric-brain-tumor-migration-and-invasion
#17
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
#18
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
#19
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
#20
Mark W Kieran
No abstract text is available yet for this article.
May 24, 2017: Neuro-oncology
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