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https://www.readbyqxmd.com/read/30101054/histone-h3-mutations-in-cancer
#1
REVIEW
Yi Ching Esther Wan, Jiaxian Liu, Kui Ming Chan
Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in chromatin-modifying enzymes has long been implicated in cancers. More recently, recurrent histone mutations have been identified in multiple cancers and have been shown to impede histone methylation. All three histone mutations (H3K27M, H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a lysine residue that is a target of methylation...
2018: Current Pharmacology Reports
https://www.readbyqxmd.com/read/30072503/evaluation-of-11-c-methionine-pet-and-anatomic-mri-associations-in-diffuse-intrinsic-pontine-glioma
#2
Christopher Tinkle, Elizabeth Duncan, Mikhail Doubrovin, Yuanyuan Han, Yimei Li, Hyun Kim, Alberto Broniscer, Scott E Snyder, Thomas E Merchant, Barry L Shulkin
The role of metabolic imaging in the diagnosis, treatment, and response assessment of diffuse intrinsic pontine glioma (DIPG) is poorly-defined. We investigated the uptake of 11 C-methionine (11 C-MET) in pediatric patients with newly diagnosed DIPG and evaluated the associations of 11 C-MET positron emission tomography (PET) metrics with conventional MRI indices and survival outcomes. Methods: Twenty-two patients with newly diagnosed DIPG were prospectively enrolled on an IRB-approved investigational study of 11 C-MET-PET...
August 2, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/30061363/melk-inhibition-in-diffuse-intrinsic-pontine-glioma
#3
Michaël H Meel, Mark C de Gooijer, Miriam Guillén Navarro, Piotr Waranecki, Marjolein Breur, Levi Buil, Laurine E Wedekind, Jos W R Twisk, Jan Koster, Rintaro Hashizume, Eric H Raabe, Angel Montero Carcaboso, Marianna Bugiani, Olaf van Tellingen, Dannis G van Vuurden, Gertjan J L Kaspers, Esther Hulleman
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor, for which no effective therapeutic options currently exist. We here determined the potential of inhibition of the maternal embryonic leucine zipper kinase (MELK) for the treatment of DIPG. EXPERIMENTAL DESIGN: We evaluated the antitumor efficacy of the small molecule MELK inhibitor OTSSP167 in vitro in patient-derived DIPG cultures, and identified the mechanism of action of MELK inhibition in DIPG by RNA sequencing of treated cells...
July 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30049282/medulloblastoma-therapy-generates-risk-of-a-poorly-prognostic-h3-wild-type-subgroup-of-diffuse-intrinsic-pontine-glioma-a-report-from-the-international-dipg-registry
#4
Hunter C Gits, Maia Anderson, Stefanie Stallard, Drew Pratt, Becky Zon, Christopher Howell, Chandan Kumar-Sinha, Pankaj Vats, Katayoon Kasaian, Daniel Polan, Martha Matuszak, Daniel E Spratt, Marcia Leonard, Tingting Qin, Lili Zhao, James Leach, Brooklyn Chaney, Nancy Yanez Escorza, Jacob Hendershot, Blaise Jones, Christine Fuller, Sarah Leary, Ute Bartels, Eric Bouffet, Torunn I Yock, Patricia Robertson, Rajen Mody, Sriram Venneti, Arul M Chinnaiyan, Maryam Fouladi, Nicholas G Gottardo, Carl Koschmann
With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years)...
July 26, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/30025492/vinorelbine-s-anti-tumor-actions-may-depend-on-the-mitotic-apoptosis-autophagy-and-inflammation-hypotheses-with-implications-for-chemo-immunotherapy-of-advanced-cancers-and-pediatric-gliomas
#5
Meric A Altinoz, Aysel Ozpinar, Ebru Emekli Alturfan, Ilhan Elmaci
Vinorelbine is a very potent chemotherapeutic agent which is used to treat a number of cancers including breast and non-small cell lung tumors. Vinorelbine mainly acts via blocking microtubules and induces a specific type of cell death called 'mitotic catastrophe/apoptosis' subsequent to mitotic slippage, which is the failure of cells to stay in a mitotic arrested state and replicating their DNA without cytokinesis. Glial tumor cells are especially sensitive to mitotic slippage. In recent years, vinorelbine demonstrated potency in pediatric optic and pontine gliomas...
July 20, 2018: Journal of Chemotherapy
https://www.readbyqxmd.com/read/30018882/beyond-the-blood-brain-barrier-the-importance-of-central-nervous-system-cns-pharmacokinetics-for-the-treatment-of-cns-tumors-including-diffuse-intrinsic-pontine-glioma
#6
REVIEW
Katherine Elizabeth Warren
Over the past decade, we have made considerable progress in establishing diffuse intrinsic pontine glioma (DIPG) as a disease entity and developing preclinical tools to interrogate potential therapeutics. However, translation to improved clinical outcomes in children with DIPG has not yet been realized. This is in part due to difficulties encountered in delivering active drugs adequately to the tumor site. However, most preclinical evaluations gloss over the fundamental concepts of central nervous system (CNS) pharmacokinetics and requirements needed to optimize drug delivery and exposure and translate this into efficacious therapy...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29967352/functional-diversity-and-cooperativity-between-subclonal-populations-of-pediatric-glioblastoma-and-diffuse-intrinsic-pontine-glioma-cells
#7
Mara Vinci, Anna Burford, Valeria Molinari, Ketty Kessler, Sergey Popov, Matthew Clarke, Kathryn R Taylor, Helen N Pemberton, Christopher J Lord, Alice Gutteridge, Tim Forshew, Diana Carvalho, Lynley V Marshall, Elizabeth Y Qin, Wendy J Ingram, Andrew S Moore, Ho-Keung Ng, Saoussen Trabelsi, Dorra H'mida-Ben Brahim, Natacha Entz-Werle, Stergios Zacharoulis, Sucheta Vaidya, Henry C Mandeville, Leslie R Bridges, Andrew J Martin, Safa Al-Sarraj, Christopher Chandler, Mariona Sunol, Jaume Mora, Carmen de Torres, Ofelia Cruz, Angel M Carcaboso, Michelle Monje, Alan Mackay, Chris Jones
The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies...
July 2, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29954445/non-inflammatory-tumor-microenvironment-of-diffuse-intrinsic-pontine-glioma
#8
Grant L Lin, Surya Nagaraja, Mariella G Filbin, Mario L Suvà, Hannes Vogel, Michelle Monje
Diffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with a median overall survival of 9-11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated a significant pathological role for adult glioma-associated macrophages. However, work over the past decade has highlighted many molecular and genomic differences between pediatric and adult high-grade gliomas. Thus, we directly compared inflammatory characteristics of DIPG and adult glioblastoma (GBM)...
June 28, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29953371/radiation-and-brain-tumors-an-overview
#9
Michael Grunert, Rebecca Kassubek, Burkhardt Danz, Burkhard Klemenz, Sebastian Hasslacher, Sebastien Stroh, Lukas Schneele, Julia Langhans, Stephanie Ströbele, Sara E Barry, Shaoxia Zhou, Klaus-Michael Debatin, Mike-Andrew Westhoff
The use of radiation is an essential part of both modern cancer diagnostic assessment and treatment. Next-generation imaging devices create 3D visualizations, allowing for better diagnoses and improved planning of precision treatment. This is particularly important for primary brain cancers such as diffuse intrinsic pontine glioma or the most common primary brain tumor, glioblastoma, because radiotherapy is often the only treatment modality that offers a significant improvement in survival and quality of life...
2018: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/29932419/h3-3k27m-mutant-proteins-reprogram-epigenome-by-sequestering-the-prc2-complex-to-poised-enhancers
#10
Dong Fang, Haiyun Gan, Liang Cheng, Jeong-Heon Lee, Hui Zhou, Jann N Sarkaria, David J Daniels, Zhiguo Zhang
Expression of histone H3.3K27M mutant proteins in human diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here, we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3...
June 22, 2018: ELife
https://www.readbyqxmd.com/read/29914797/convection-enhanced-delivery-chemosurgery-in-diffuse-intrinsic-pontine-glioma
#11
Dannis G van Vuurden
No abstract text is available yet for this article.
June 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29914796/convection-enhanced-delivery-for-diffuse-intrinsic-pontine-glioma-a-single-centre-dose-escalation-phase-1-trial
#12
Mark M Souweidane, Kim Kramer, Neeta Pandit-Taskar, Zhiping Zhou, Sofia Haque, Pat Zanzonico, Jorge A Carrasquillo, Serge K Lyashchenko, Sunitha B Thakur, Maria Donzelli, Ryan S Turner, Jason S Lewis, Nai-Kong V Cheung, Steven M Larson, Ira J Dunkel
BACKGROUND: Diffuse intrinsic pontine glioma is one of the deadliest central nervous system tumours of childhood, with a median overall survival of less than 12 months. Convection-enhanced delivery has been proposed as a means to efficiently deliver therapeutic agents directly into the brainstem while minimising systemic exposure and associated toxic effects. We did this study to evaluate the safety of convection-enhanced delivery of a radioimmunotherapy agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma...
June 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29904623/cdk4-6-and-pdgfra-signaling-as-therapeutic-targets-in-diffuse-intrinsic-pontine-glioma
#13
REVIEW
Christine Hoeman, Chen Shen, Oren J Becher
Diffuse intrinsic pontine gliomas (DIPGs) are incurable childhood brain tumors, whereby the standard of care is focal radiation, a treatment that provides temporary relief for most patients. Surprisingly, decades of clinical trials have failed to identify additional therapies that can prolong survival in this disease. In this conference manuscript, we discuss how genetic engineered mouse modeling techniques with the use of a retroviral gene delivery system can help dissect the complex pathophysiology of this disease...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29897054/corrigendum-immune-response-generated-with-the-administration-of-autologous-dendritic-cells-pulsed-with-an-allogenic-tumoral-cell-lines-lysate-in-patients-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#14
Daniel Benitez-Ribas, Raquel Cabezón, Georgina Flórez-Grau, Mari Carmen Molero, Patricia Puerta, Antonio Guillen, E Azucena González-Navarro, Sonia Paco, Angel M Carcaboso, Vicente Santa-Maria Lopez, Ofelia Cruz, Carmen de Torres, Noelia Salvador, Manel Juan, Jaume Mora, Andres Morales La Madrid
[This corrects the article on p. 127 in vol. 8, PMID: 29755954.].
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29868485/the-integration-of-biology-into-the-treatment-of-diffuse-intrinsic-pontine-glioma-a-review-of-the-north-american-clinical-trial-perspective
#15
REVIEW
Jessica Clymer, Mark W Kieran
Dramatic advances in the molecular analysis of diffuse intrinsic pontine glioma have occurred over the last decade and resulted in the identification of potential therapeutic targets. In spite of these advances, no significant improvement in the outcome has been achieved and median survival remains approximately 10 months. An understanding of the approaches that have been taken to date, why they failed, and how that information can lead the field forward is critical if we are to change the status quo . In this review, we will discuss the clinical trial landscape in North America with an overview of historical approaches that failed and what might account for this failure...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29864474/focused-ultrasound-enabled-delivery-of-radiolabeled-nanoclusters-to-the-pons
#16
Dezhuang Ye, Deborah Sultan, Xiaohui Zhang, Yimei Yue, Gyu Seong Heo, Satya V V N Kothapalli, Hannah Luehmann, Yuan-Chuan Tai, Joshua B Rubin, Yongjian Liu, Hong Chen
The goal of this study was to establish the feasibility of integrating focused ultrasound (FUS)-mediated delivery of 64 Cu-integrated gold nanoclusters (64 Cu-AuNCs) to the pons for in vivo quantification of the nanocluster brain uptake using positron emission tomography (PET) imaging. FUS was targeted at the pons for the blood-brain barrier (BBB) disruption in the presence of systemically injected microbubbles, followed by the intravenous injection of 64 Cu-AuNCs. The spatiotemporal distribution of the 64 Cu-AuNCs in the brain was quantified using in vivo microPET/CT imaging at different time points post injection...
August 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29848907/mgmt-expression-contributes-to-temozolomide-resistance-in-h3k27m-mutant-diffuse-midline-gliomas-and-mgmt-silencing-to-temozolomide-sensitivity-in-idh-mutant-gliomas
#17
Hideaki Abe, Manabu Natsumeda, Yu Kanemaru, Jun Watanabe, Yoshihiro Tsukamoto, Masayasu Okada, Junichi Yoshimura, Makoto Oishi, Yukihiko Fujii
Histone H3 mutations are frequently found in diffuse midline gliomas (DMGs), which include diffuse intrinsic pontine gliomas and thalamic gliomas. These tumors have dismal prognoses. Recent evidence suggests that one reason for the poor prognoses is that O6 -methylguanine-DNA methyltransferase (MGMT) promoter frequently lacks methylation in DMGs. This review compares the epigenetic changes brought about by histone mutations to those by isocitrate dehydrogenase-mutant gliomas, which frequently have methylated MGMT promoters and are known to be sensitive to temozolomide...
July 15, 2018: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/29802243/live-cell-single-molecule-dynamics-of-pcg-proteins-imposed-by-the-dipg-h3-3k27m-mutation
#18
Roubina Tatavosian, Huy Nguyen Duc, Thao Ngoc Huynh, Dong Fang, Benjamin Schmitt, Xiaodong Shi, Yiming Deng, Christopher Phiel, Tingting Yao, Zhiguo Zhang, Haobin Wang, Xiaojun Ren
Over 80% of diffuse intrinsic pontine gliomas (DIPGs) harbor a point mutation in histone H3.3 where lysine 27 is substituted with methionine (H3.3K27M); however, how the mutation affects kinetics and function of PcG proteins remains elusive. We demonstrate that H3.3K27M prolongs the residence time and search time of Ezh2, but has no effect on its fraction bound to chromatin. In contrast, H3.3K27M has no effect on the residence time of Cbx7, but prolongs its search time and decreases its fraction bound to chromatin...
May 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29774497/safety-of-commercial-airflight-in-patients-with-brain-tumors-a-case-series
#19
Michelle Phillips, Marlon Saria, Amy Eisenberg, Daniel F Kelly, Garni Barkhoudarian
INTRODUCTION: Patients with intracranial masses are often advised to avoid airflight due to concerns of worsening neurological symptoms or deterioration. However, many patients often travel cross-country or internationally to tertiary care centers for definitive care. This study assesses the safety of commercial airflight for brain and skull base tumor patients without severe or progressive neurological deficits. METHODS: Patients that had traveled to our institution for surgery via commercial airflight from 2014 to 2017 were identified...
May 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29767306/correction-to-results-of-nimotuzumab-and-vinorelbine-radiation-and-re-irradiation-for-diffuse-pontine-glioma-in-childhood
#20
Maura Massimino, Veronica Biassoni, Rosalba Miceli, Elisabetta Schiavello, Monika Warmuth-Metz, Piergiorgio Modena, Michela Casanova, Emilia Pecori, Felice Giangaspero, Manila Antonelli, Francesca Romana Buttarelli, Paolo Potepan, Bianca Pollo, Raffaele Nunziata, Filippo Spreafico, Marta Podda, Andrea Anichini, Carlo Alfredo Clerici, Iacopo Sardi, Loris De Cecco, Udo Bode, Ferdinand Bach, Lorenza Gandola
The therapeutic experience reported in the paper was conceived after the use of nimotuzumab and radiotherapy (BSCPED-05 international multicentric trial, EUDRACT 2005-003100-11) in 2009 when we decided to explore the activity of the same combination plus vinorelbine (see the paper for the rationale).
May 16, 2018: Journal of Neuro-oncology
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