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Diffuse Intrinsic Pontine Glioma

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https://www.readbyqxmd.com/read/29143272/preliminary-results-of-immune-modulating-antibody-mdv9300-pidilizumab-treatment-in-children-with-diffuse-intrinsic-pontine-glioma
#1
Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Helen Toledano, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Michael Weintraub, Mony Benifla
Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study...
November 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29118968/combination-of-ezh2-inhibitor-and-bet-inhibitor-for-treatment-of-diffuse-intrinsic-pontine-glioma
#2
Yaqin Zhang, Weijie Dong, Junying Zhu, Lizhu Wang, Xinjian Wu, Hong Shan
Background: Diffuse intrinsic pontine glioma is an infiltrative, often high-grade glioma of the brainstem that is not amenable to surgical resection. The current treatment of DIPG by radiation therapy showed dramatically improvement of patient's condition, however, the tumor recurs rapidly. More and more studies are focused on the genetic and epigenetic drivers of DIPGs, which may provide more and more novel therapy target for DIPG. EZH2 has been proved to be a potential therapeutic target for H3K27M-mutant pediatric gliomas recently...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29100338/patient-derived-dipg-cells-preserve-stem-like-characteristics-and-generate-orthotopic-tumors
#3
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, Junting 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...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29090526/a-pediatric-brain-tumor-consortium-phase-ii-trial-of-capecitabine-rapidly-disintegrating-tablets-with-concomitant-radiation-therapy-in-children-with-newly-diagnosed-diffuse-intrinsic-pontine-gliomas
#4
Lindsay B Kilburn, Mehmet Kocak, Patricia Baxter, Tina Young Poussaint, Arnold C Paulino, Christine McIntyre, Annabelle Lemenuel-Diot, Christine Lopez-Diaz, Larry Kun, Murali Chintagumpala, Jack M Su, Alberto Broniscer, Justin N Baker, Eugene I Hwang, Maryam Fouladi, James M Boyett, Susan M Blaney
BACKGROUND: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). PATIENTS AND METHODS: Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m(2) /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT...
November 1, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29069732/characterization-of-the-transcriptional-and-metabolic-responses-of-pediatric-high-grade-gliomas-to-mtor-hif-1%C3%AE-axis-inhibition
#5
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063425/correction-to-a-phase-i-ii-study-of-gemcitabine-during-radiotherapy-in-children-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#6
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
In Table 2 of the original publication, there were errors in the baseline scores for the PedsQL TM 3.0 Cancer Module questionnaire, so a corrected version of Table 2 is shown in this erratum. In the subcategories of the PedsQL TM 3.0 Cancer Module questionnaire, nausea and fear of procedure did not score significantly lower after treatment compared to baseline. So, based on the corrected data in Table 2, there was no significant decrease in the total score of the cancer questionnaire, and this statement in the previous manuscript was incorrect...
October 23, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29057192/palliative-care-options-for-a-young-adult-patient-with-a-diffuse-intrinsic-pontine-glioma
#7
Julian Sison, Hung Tran, Ashley Margol, Nishant Tiwari, Karla M Garcia, Jennifer Cotter, Erin Kiehna, Arthur J Olch, Kenneth Wong
Diffuse intrinsic pontine gliomas (DIPGs) are rare but devastating brain tumors that occur primarily in children. These gliomas have poor prognoses and present options focus on palliation of symptoms and prolongation of life. Here, we present a case of a 16-year-old female diagnosed with a DIPG whose age group has been mostly left out of discussions regarding psychosocial support options. This report is meant to start a conversation about the different support options available at our institution that have shown promising results in the literature for palliative care applications...
August 18, 2017: Curēus
https://www.readbyqxmd.com/read/29022050/concurrent-radiotherapy-with-temozolomide-vs-concurrent-radiotherapy-with-a%C3%A2-cisplatinum-based-polychemotherapy-regimen-acute-toxicity-in-pediatric-high-grade-glioma-patients
#8
Clemens Seidel, André O von Bueren, Sabrina Bojko, Marion Hoffmann, Torsten Pietsch, Gerrit H Gielen, Monika Warmuth-Metz, Brigitte Bison, Rolf-D Kortmann, Christof M Kramm
PURPOSE: As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments. METHODS: Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials...
October 11, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28968963/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#9
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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966033/integrated-molecular-meta-analysis-of-1-000-pediatric-high-grade-and-diffuse-intrinsic-pontine-glioma
#10
Alan Mackay, Anna Burford, Diana Carvalho, Elisa Izquierdo, Janat Fazal-Salom, Kathryn R Taylor, Lynn Bjerke, Matthew Clarke, Mara Vinci, Meera Nandhabalan, Sara Temelso, Sergey Popov, Valeria Molinari, Pichai Raman, Angela J Waanders, Harry J Han, Saumya Gupta, Lynley Marshall, Stergios Zacharoulis, Sucheta Vaidya, Henry C Mandeville, Leslie R Bridges, Andrew J Martin, Safa Al-Sarraj, Christopher Chandler, Ho-Keung Ng, Xingang Li, Kun Mu, Saoussen Trabelsi, Dorra H'mida-Ben Brahim, Alexei N Kisljakov, Dmitry M Konovalov, Andrew S Moore, Angel Montero Carcaboso, Mariona Sunol, Carmen de Torres, Ofelia Cruz, Jaume Mora, Ludmila I Shats, João N Stavale, Lucas T Bidinotto, Rui M Reis, Natacha Entz-Werle, Michael Farrell, Jane Cryan, Darach Crimmins, John Caird, Jane Pears, Michelle Monje, Marie-Anne Debily, David Castel, Jacques Grill, Cynthia Hawkins, Hamid Nikbakht, Nada Jabado, Suzanne J Baker, Stefan M Pfister, David T W Jones, Maryam Fouladi, André O von Bueren, Michael Baudis, Adam Resnick, Chris Jones
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28959975/targeting-neuronal-activity-regulated-neuroligin-3-dependency-in-high-grade-glioma
#11
Humsa S Venkatesh, Lydia T Tam, Pamelyn J Woo, James Lennon, Surya Nagaraja, Shawn M Gillespie, Jing Ni, Damien Y Duveau, Patrick J Morris, Jean J Zhao, Craig J Thomas, Michelle Monje
High-grade gliomas (HGG) are a devastating group of cancers, and represent the leading cause of brain tumour-related death in both children and adults. Therapies aimed at mechanisms intrinsic to glioma cells have translated to only limited success; effective therapeutic strategies will need also to target elements of the tumour microenvironment that promote glioma progression. Neuronal activity promotes the growth of a range of molecularly and clinically distinct HGG types, including adult and paediatric glioblastoma (GBM), anaplastic oligodendroglioma, and diffuse intrinsic pontine glioma (DIPG)...
September 28, 2017: Nature
https://www.readbyqxmd.com/read/28947983/deceptive-morphologic-and-epigenetic-heterogeneity-in-diffuse-intrinsic-pontine-glioma
#12
Marianna Bugiani, Sophie E M Veldhuijzen van Zanten, Viola Caretti, Pepijn Schellen, Eleonora Aronica, David P Noske, William P Vandertop, Gertjan J L Kaspers, Dannis G van Vuurden, Pieter Wesseling, Esther Hulleman
Historically, the diagnosis of diffuse intrinsic pontine glioma (DIPG) was based on typical imaging findings and clinical characteristics instead of pathology. However, the discovery of mutations in histone H3 variants, and the availability of tumor material for molecular analysis, has led to a paradigm shift in DIPG research and clinical practice. Using data from whole-brain autopsies in a series of nine DIPG patients with known histone mutational status, we here aim to review histopathological characteristics with special focus on intratumoral heterogeneity (ITH) and histone 3 K27 trimethylation (H3 K27me3)...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28947132/culture-methods-of-diffuse-intrinsic-pontine-glioma-cells-determine-response-to-targeted-therapies
#13
Michaël H Meel, A Charlotte P Sewing, Piotr Waranecki, Dennis S Metselaar, Laurine E Wedekind, Jan Koster, Dannis G van Vuurden, Gertjan J L Kaspers, Esther Hulleman
Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer occurring mainly in children, for which there currently is no effective therapy. Current efforts to develop novel therapeutics for this tumor make use of primary cultures of DIPG cells, maintained either as adherent monolayer in serum containing medium, or as neurospheres in serum-free medium. In this manuscript, we demonstrate that the response of DIPG cells to targeted therapies in vitro is mainly determined by the culture conditions...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28881750/new-in-vivo-avatars-of-diffuse-intrinsic-pontine-gliomas-dipg-from-stereotactic-biopsies-performed-at-diagnosis
#14
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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28856152/positron-emission-tomography-imaging-in-diffuse-intrinsic-pontine-glioma
#15
EDITORIAL
Norbert Galldiks, Carina Stegmayr, Antje Willuweit, Karl-Josef Langen
No abstract text is available yet for this article.
August 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28853208/clinical-outcomes-and-toxicity-following-palliative-radiotherapy-for-childhood-cancers
#16
Kimberley S Mak, Stephanie W Lee, Tracy A Balboni, Karen J Marcus
BACKGROUND: Few reports of palliative radiotherapy (RT) for pedialltric malignancies have been published. We described clinical indications, outcomes, and toxicities for children who received palliative RT. PROCEDURE: Pediatric patients (age ≤18 years) treated with palliative RT for incurable cancer from January 1 2008 to February 26, 2014 were included. Diagnosis, details of RT, treatment response, toxicity, and survival were retrospectively reviewed. RESULTS: Forty-six patients received 76 RT courses...
August 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28821206/contemporary-survival-endpoints-an-international-diffuse-intrinsic-pontine-glioma-registry-study
#17
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
#18
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
#19
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
#20
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
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