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https://www.readbyqxmd.com/read/29165288/treatment-related-noncontiguous-radiologic-changes-in-children-with-diffuse-intrinsic-pontine-glioma-treated-with-expanded-irradiation-fields-and-antiangiogenic-therapy
#1
Zoltan Patay, Thomas E Merchant, Rosa Nguyen, Christopher R Pierson, Arzu Onar-Thomas, Alberto Broniscer
PURPOSE: We previously reported the cases of 3 children with diffuse intrinsic pontine glioma (DIPG) in whom noncontiguous treatment-related abnormalities (NCTRAs) developed in the brain after expanded-field radiation therapy (RT). To investigate the occurrence and putative mechanism of NCTRAs, we reviewed brain magnetic resonance imaging studies of patients with DIPG treated in 2 consecutive phase I clinical trials (trials 1 and 2). METHODS AND MATERIALS: The 55 children included in these trials received small-molecule inhibitors: vandetanib in trial 1 (n=32; mean age 6...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29164272/signaling-pathways-and-mesenchymal-transition-in-pediatric-high-grade-glioma
#2
REVIEW
Michaël H Meel, Sophie A Schaper, Gertjan J L Kaspers, Esther Hulleman
Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible...
November 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29164054/effective-drug-delivery-in-diffuse-intrinsic-pontine-glioma-a-theoretical-model-to-identify-potential-candidates
#3
Fatma E El-Khouly, Dannis G van Vuurden, Thom Stroink, Esther Hulleman, Gertjan J L Kaspers, N Harry Hendrikse, Sophie E M Veldhuijzen van Zanten
Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED) may increase their therapeutic potential...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29151166/t2-weighted-images-are-superior-to-other-mr-image-types-for-the-determination-of-diffuse-intrinsic-pontine-glioma-intratumoral-heterogeneity
#4
Stephen Harward, S Harrison Farber, Michael Malinzak, Oren Becher, Eric M Thompson
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) remains the main cause of death in children with brain tumors. Given the inefficacy of numerous peripherally delivered agents to treat DIPG, convection enhanced delivery (CED) of therapeutic agents is a promising treatment modality. The purpose of this study was to determine which MR imaging type provides the best discrimination of intratumoral heterogeneity to guide future stereotactic implantation of CED catheters into the most cellular tumor regions...
November 18, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#5
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29143272/preliminary-results-of-immune-modulating-antibody-mdv9300-pidilizumab-treatment-in-children-with-diffuse-intrinsic-pontine-glioma
#6
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
#7
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
#8
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
#9
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/29057192/palliative-care-options-for-a-young-adult-patient-with-a-diffuse-intrinsic-pontine-glioma
#10
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
#11
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
#12
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/28959975/targeting-neuronal-activity-regulated-neuroligin-3-dependency-in-high-grade-glioma
#13
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
#14
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
#15
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
#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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28818988/multiregional-tumor-drug-uptake-imaging-by-pet-and-microvascular-morphology-in-end-stage-diffuse-intrinsic-pontine-glioma
#17
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
#18
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
#19
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
#20
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
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