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https://www.readbyqxmd.com/read/30318760/longitudinal-evaluation-of-tumor-microenvironment-in-rat-focal-brainstem-glioma-using-diffusion-and-perfusion-mri
#1
Kulam Najmudeen Magdoom, Francisco Delgado, Ana C Bohórquez, Alec C Brown, Paul R Carney, Carlos Rinaldi, Thomas H Mareci, James R Ewing, Malisa Sarntinoranont
BACKGROUND: Brainstem gliomas are aggressive and difficult to treat. Growth of these tumors may be characterized with MRI methods. PURPOSE: To visualize longitudinal changes in tumor volume, vascular leakiness, and tissue microstructure in an animal model of brainstem glioma. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Male Sprague-Dawley rats (n = 9) were imaged with 9L gliosarcoma cells infused into the pontine reticular formation of the brainstem...
October 14, 2018: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/30254491/combined-use-of-cdk4-6-and-mtor-inhibitors-induce-synergistic-growth-arrest-of-diffuse-intrinsic-pontine-glioma-cells-via-mutual-downregulation-of-mtorc1-activity
#2
Daniel J Asby, Clare L Killick-Cole, Lisa J Boulter, William Gb Singleton, Claire A Asby, Marcella J Wyatt, Neil U Barua, Alison S Bienemann, Steven S Gill
Background: Diffuse intrinsic pontine glioma (DIPG) is a lethal type of pediatric brain tumor that is resistant to conventional chemotherapies. Palbociclib is a putative novel DIPG treatment that restricts the proliferation of rapidly dividing cancer cells via selective inhibition of cyclin-dependent kinase (CDK) 4 and CDK6. However, implementing palbociclib as a monotherapy for DIPG is unfeasible, as CDK4/6 inhibitor resistance is commonplace and palbociclib does not readily cross the blood-brain barrier (BBB) or persist in the central nervous system...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30210988/fluorescein-guided-surgery-for-pediatric-brainstem-gliomas-preliminary-study-and-technical-notes
#3
Zhan Xue, Lu Kong, Chang-Cun Pan, Zhen Wu, Jun-Ting Zhang, Li-Wei Zhang
Introduction  Brainstem gliomas (BsG) account for 10 to 15% of pediatric brain tumors. Surgery is the preferred treatment for focal and exophytic lesions. Sodium fluorescein has been proven safe and effective in resection of malignant brain tumors. Objective  The objective was to o analyze the safety and effectiveness of this approach, to evaluate intraoperative fluorescein imaging, and to measure the safety of chosen dose for pediatric patients. Methods  Twelve cases were enrolled between March 2014 and September 2016 in Beijing Tiantan Hospital...
October 2018: Journal of Neurological Surgery. Part B, Skull Base
https://www.readbyqxmd.com/read/30192215/tumor-dissemination-through-surgical-tracts-in-diffuse-intrinsic-pontine-glioma
#4
Maria-Jesus Lobon-Iglesias, Vicente Santa-Maria Lopez, Patricia Puerta Roldan, Santiago Candela-Cantó, Monica Ramos-Albiac, Marta Gomez-Chiari, Stephanie Puget, Stephanie Bolle, Liliana Goumnerova, Mark W Kieran, Ofelia Cruz, Jacques Grill, Andres Morales La Madrid
OBJECTIVE Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive and lethal brainstem tumor in children. In the 1980s, routine biopsy at presentation was abandoned since it was claimed "unnecessary" for diagnosis. In the last decade, however, several groups have reincorporated this procedure as standard of care or in the context of clinical trials. Expert neurosurgical teams report no mortality and acceptable morbidity, and no relevant complications have been previously described. The aim of this study was to review needle tract dissemination as a potential complication in DIPG...
September 7, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/30174560/measuring-tumor-metabolism-in-pediatric-diffuse-intrinsic-pontine-glioma-using-hyperpolarized-carbon-13-mr-metabolic-imaging
#5
Adam W Autry, Rintaro Hashizume, C David James, Peder E Z Larson, Daniel B Vigneron, Ilwoo Park
Objective: The purpose of this study was to demonstrate the feasibility of using hyperpolarized carbon-13 (13 C) metabolic imaging with [1-13 C]-labeled pyruvate for evaluating real-time in vivo metabolism of orthotopic diffuse intrinsic pontine glioma (DIPG) xenografts. Materials and Methods: 3D 13 C magnetic resonance spectroscopic imaging (MRSI) data were acquired on a 3T scanner from 8 rats that had been implanted with human-derived DIPG cells in the brainstem and 5 healthy controls, following injection of 2...
2018: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/30169876/characterization-of-the-immune-microenvironment-of-diffuse-intrinsic-pontine-glioma-implications-for-development-of-immunotherapy
#6
Nicole A P Lieberman, Kole DeGolier, Heather M Kovar, Amira Davis, Virginia Hoglund, Jeffrey Stevens, Conrad Winter, Gail Deutsch, Scott N Furlan, Nicholas A Vitanza, Sarah E S Leary, Courtney A Crane
Background: Diffuse Intrinsic Pontine Glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG tumors cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically, however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor expression in pediatric low- and high-grade gliomas and DIPG...
August 28, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/30138731/population-based-study-determining-predictors-of-cancer-specific-mortality-and-survival-in-pediatric-high-grade-brainstem-glioma
#7
Russell Maxwell, Andrew S Luksik, Tomas Garzon-Muvdi, Wuyang Yang, Judy Huang, Chetan Bettegowda, George I Jallo, Stephanie A Terezakis, Mari L Groves
BACKGROUND: Pediatric high-grade brainstem gliomas are aggressive tumors with dismal prognoses. Large-scale studies are needed to further characterize these tumors and determine factors influencing cancer-specific mortality and survival at varying time points. METHODS: We used the SEER (Surveillance Epidemiology and End Results) database to conduct a population-based study of pediatric patients with histologically confirmed anaplastic astrocytoma or glioblastoma tumors located within the brainstem...
August 20, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/30124166/bioinformatics-analysis-of-microarray-data-to-reveal-the-pathogenesis-of-diffuse-intrinsic-pontine-glioma
#8
Li Wei, Fei He, Wen Zhang, Wenhua Chen, Bo Yu
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. METHODS: The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool...
August 20, 2018: Biological Research
https://www.readbyqxmd.com/read/30101054/histone-h3-mutations-in-cancer
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
August 2018: Nature Medicine
https://www.readbyqxmd.com/read/29954445/non-inflammatory-tumor-microenvironment-of-diffuse-intrinsic-pontine-glioma
#16
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
#17
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
#18
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
#19
Dannis G van Vuurden
No abstract text is available yet for this article.
August 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
#20
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...
August 2018: Lancet Oncology
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