keyword
https://read.qxmd.com/read/32588986/the-role-of-diffusion-tensor-imaging-metrics-in-the-discrimination-between-cerebellar-medulloblastoma-and-brainstem-glioma
#21
Nguyen Minh Duc
BACKGROUND: Differentiation between cerebellar medulloblastoma and brainstem glioma is necessary for certain clinical circumstances. We aimed to evaluate the function of diffusion tensor imaging (DTI) metrics in the differentiation between cerebellar medulloblastomas and brainstem gliomas in children. PROCEDURE: The institutional review board approved this prospective study. Brain magnetic resonance imaging (MRI), including DTI, was assessed in 40 patients, who were divided into two groups: a medulloblastoma group (group 1, n = 25) and a brainstem glioma group (group 2, n = 15)...
June 26, 2020: Pediatric Blood & Cancer
https://read.qxmd.com/read/32555164/the-integrated-genomic-and-epigenomic-landscape-of-brainstem-glioma
#22
Lee H Chen, Changcun Pan, Bill H Diplas, Cheng Xu, Landon J Hansen, Yuliang Wu, Xin Chen, Yibo Geng, Tao Sun, Yu Sun, Peng Zhang, Zhen Wu, Junting Zhang, Deling Li, Yang Zhang, Wenhao Wu, Yu Wang, Guangyu Li, Jie Yang, Xiaoyue Wang, Ce Xu, Sizhen Wang, Matthew S Waitkus, Yiping He, Roger E McLendon, David M Ashley, Hai Yan, Liwei Zhang
Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, including Diffuse Intrinsic Pontine Gliomas. Here we report, from DNA methylation data, distinct clusters termed H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. The majority of tumors within H3-Pons and-H3-Medulla harbors H3F3A mutations but shows distinct methylation patterns that correlate with anatomical localization within the pons or medulla, respectively...
June 17, 2020: Nature Communications
https://read.qxmd.com/read/32459315/ad-cd40l-mobilizes-cd4-t-cells-for-the-treatment-of-brainstem-tumors
#23
Phonphimon Wongthida, Matthew R Schuelke, Christopher B Driscoll, Timothy Kottke, Jill M Thompson, Jason Tonne, Cathy Stone, Amanda L Huff, Cynthia Wetmore, James A Davies, Alan L Parker, Laura Evgin, Richard G Vile
BACKGROUND: Diffuse Midline Glioma, formerly Diffuse Intrinsic Pontine Glioma (DIPG), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated 1) whether direct delivery of adenovirus expressing CD40L (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and, 2) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem. METHODS: Syngeneic gliomas in the brainstems of immune competent mice were treated with Ad-CD40L and survival, toxicity and immune profiles determined...
May 27, 2020: Neuro-oncology
https://read.qxmd.com/read/32349240/characterization-of-the-blood-brain-barrier-integrity-and-the-brain-transport-of-sn-38-in-an-orthotopic-xenograft-rat-model-of-diffuse-intrinsic-pontine-glioma
#24
Catarina Chaves, Xavier Declèves, Meryam Taghi, Marie-Claude Menet, Joelle Lacombe, Pascale Varlet, Nagore G Olaciregui, Angel M Carcaboso, Salvatore Cisternino
The blood-brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed 1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14 C]-sucrose as measures of BBB integrity, and 2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3 H]-SN-38...
April 27, 2020: Pharmaceutics
https://read.qxmd.com/read/32332014/therapeutic-efficacy-of-immune-stimulatory-thymidine-kinase-and-fms-like-tyrosine-kinase-3-ligand-tk-flt3l-gene-therapy-in-a-mouse-model-of-high-grade-brainstem-glioma
#25
Flor Mendez, Padma Kadiyala, Felipe J Nunez, Stephen Carney, Fernando M Nunez, Jessica C Gauss, Ramya Ravindran, Sheeba Pawar, Marta Edwards, Maria Belen Garcia-Fabiani, Santiago Haase, Pedro R Lowenstein, Maria G Castro
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, ACVR1-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy. EXPERIMENTAL DESIGN: We utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNAseq analysis on neurospheres (NS) harboring mACVR1...
April 24, 2020: Clinical Cancer Research
https://read.qxmd.com/read/32328455/the-epidemiological-characteristics-and-prognostic-factors-of-low-grade-brainstem-glioma-a-real-world-study-of-pediatric-and-adult-patients
#26
Zhuoyi Liu, Songshan Feng, Jing Li, Hui Cao, Jun Huang, Fan Fan, Li Cheng, Zhixiong Liu, Quan Cheng
Purpose: Our current understanding of low-grade brainstem glioma (LGBSG) is still limited. This study aimed to conduct a large-scale population-based real-world study to understand the epidemiological characteristics of LGBSG and determine the predictive factors of cancer-specific survival (CSS) and overall survival (OS) of LGBSG patients. Patients and Methods: We used Surveillance Epidemiology and End Results database to conduct this study of patients with histologically confirmed LGBSG. Patient demographics, tumor characteristics, and treatment options were compared between pediatric and adult patients...
2020: Frontiers in Oncology
https://read.qxmd.com/read/32311581/identification-of-new-therapeutic-targets-and-natural-compounds-against-diffuse-intrinsic-pontine-glioma-dipg
#27
Jungang Chen, Zhen Lin, Lindsey Barrett, Lu Dai, Zhiqiang Qin
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor which accounts for about 10-20% of childhood brain tumors. The survival rate for DIPG remains very poor, with a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of a large number of clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care for DIPG. In the current study, we screened a natural product library and for the first time identified 6 natural compounds displaying inhibitory effects on DIPG proliferation and anchorage-independent growth through inducing tumor cell apoptosis and cell cycle arrest...
April 13, 2020: Bioorganic Chemistry
https://read.qxmd.com/read/32300062/nonoptic-pathway-tumors-in-children-with-neurofibromatosis-type-1
#28
Jasia Mahdi, Manu S Goyal, Jennifer Griffith, Stephanie M Morris, David H Gutmann
OBJECTIVE: To define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1). METHODS: We performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed...
April 16, 2020: Neurology
https://read.qxmd.com/read/32228694/the-molecular-characteristics-of-spinal-cord-gliomas-with-or-without-h3-k27m-mutation
#29
Rui-Chao Chai, Yao-Wu Zhang, Yu-Qing Liu, Yu-Zhou Chang, Bo Pang, Tao Jiang, Wen-Qing Jia, Yong-Zhi Wang
Due to the rare incidence of spinal cord astrocytomas, their molecular features remain unclear. Here, we characterized the landscapes of mutations in H3 K27M, isocitrate dehydrogenase 1 (IDH1) R132H, BRAF V600E, and the TERT promoter in 83 diffuse spinal cord astrocytic tumors. Among these samples, thirty-five patients had the H3 K27M mutation; this mutant could be observed in histological grade II (40%), III (40%), and IV (20%) astrocytomas. IDH1 mutations were absent in 58 of 58 cases tested. The BRAF V600E mutation (7/57) was only observed in H3-wildtype astrocytomas, and was associated with a better prognosis in all histological grade II/III astrocytomas...
March 30, 2020: Acta Neuropathologica Communications
https://read.qxmd.com/read/32196609/h3k27m-mutant-diffuse-midline-glioma-a-case-report
#30
Y Luo, L Zeng, X-Q Xie, F Wang, Y-Z Liu, J-B Kang, X-F Li, D-B Wu, B-L Qu
OBJECTIVE: Diffuse midline glioma with H3K27M mutation is a new tumor type of WHO central nervous system tumor classification. It often occurs in the midline structure and usually has a poor prognosis. CASE REPORT: A 38-year-old male patient presented with 2 years history of right limb with facial numbness, tumors in the left thalamic region and lateral ventricle was detected by imaging. The patient underwent the first surgery. RESULTS: The pathological examination results: Glioblastoma...
March 2020: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/32192255/en-mann-i-60-%C3%A3-rene-med-gangvansker-dysartri-og-lett-kognitiv-svikt
#31
Ludmila Nordaa, Elin Bjelland Forsaa, Audun Odland, Soffien Ajmi
BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is an immune-mediated, treatable and inflammatory CNS disease first reported by Pittock et al. (2010). CASE PRESENTATION: We describe a 66-year-old man with previous history of diabetes, atrial fibrillation and hypertension, who was admitted to hospital with reduced general condition. He had experienced dizziness and unstable gait for a year, and had been periodically confused, especially in the previous month...
March 17, 2020: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
https://read.qxmd.com/read/32166329/pharmacologic-inhibition-of-lysine-specific-demethylase-1-lsd1-as-a-therapeutic-and-immune-sensitization-strategy-in-pediatric-high-grade-glioma-phgg
#32
Cavan P Bailey, Mary Figueroa, Achintyan Gangadharan, Yanwen Yang, Megan M Romero, Bridget A Kennis, Sridevi Yadavilli, Verlene Henry, Tiara Collier, Michelle Monje, Dean A Lee, Linghua Wang, Javad Nazarian, Vidya Gopalakrishnan, Wafik Zaky, Oren J Becher, Joya Chandra
BACKGROUND: Diffuse midline gliomas (DMG), including brainstem DIPG, are incurable pediatric high grade gliomas (pHGG). Mutations in the H3 histone tail (H3.1/3.3-K27M) are a feature of DIPG, rendering them therapeutically sensitive to small-molecule inhibition of chromatin modifiers. Pharmacological inhibition of lysine specific demethylase-1 (LSD1) is clinically relevant but has not been carefully investigated in pHGG or DIPG. METHODS: Patient-derived DIPG cell lines, orthotopic mouse models, and pHGG datasets were used to evaluate effects of LSD1 inhibitors on cytotoxicity and immune gene expression...
March 13, 2020: Neuro-oncology
https://read.qxmd.com/read/32118205/noninvasive-quantification-of-sirt1-expression-activity-and-pharmacologic-inhibition-in-a-rat-model-of-intracerebral-glioma-using-2-18-f-bzaha-pet-ct-mri
#33
Maxwell T Laws, Robin E Bonomi, David J Gelovani, Jeremy Llaniguez, Xin Lu, Thomas Mangner, Juri G Gelovani
Background: Several studies demonstrated that glioblastoma multiforme progression and recurrence is linked to epigenetic regulatory mechanisms. Sirtuin 1 (SIRT1) plays an important role in glioma progression, invasion, and treatment response and is a potential therapeutic target. The aim of this study is to test the feasibility of 2-[18 F]BzAHA for quantitative imaging of SIRT1 expression-activity and monitoring pharmacologic inhibition in a rat model of intracerebral glioma. Methods: Sprague Dawley rats bearing 9L ( N = 12) intracerebral gliomas were injected with 2-[18 F]BzAHA (300-500 µCi/animal i...
January 2020: Neuro-oncology advances
https://read.qxmd.com/read/32078691/epigenetic-reprogramming-and-chromatin-accessibility-in-pediatric-diffuse-intrinsic-pontine-gliomas-a-neural-developmental-disease
#34
Flor M Mendez, Felipe J Núñez, Maria B Garcia-Fabiani, Santiago Haase, Stephen Carney, Jessica C Gauss, Oren J Becher, Pedro R Lowenstein, Maria G Castro
Diffuse intrinsic pontine glioma (DIPG) is a rare but deadly pediatric brainstem tumor. To date, there is no effective therapy for DIPG. Transcriptomic analyses have revealed DIPGs have a distinct profile from other pediatric high-grade gliomas occurring in the cerebral hemispheres. These unique genomic characteristics coupled with the younger median age group suggest that DIPG has a developmental origin. The most frequent mutation in DIPG is a lysine to methionine (K27M) mutation that occurs on H3F3A and HIST1H3B/C, genes encoding histone variants...
February 20, 2020: Neuro-oncology
https://read.qxmd.com/read/32050461/retrospective-and-randomized-analysis-of-influence-and-correlation-of-clinical-and-molecular-prognostic-factors-in-a-mono-operative-series-of-122-patients-with-glioblastoma-treated-with-str-or-gtr
#35
Maurizio Salvati, Placido Bruzzaniti, Michela Relucenti, Mariagrazia Nizzola, Pietro Familiari, Marco Giugliano, Anthony Kevin Scafa, Santi Galletta, Xiaobo Li, Rui Chen, Claudio Barbaranelli, Alessandro Frati, Antonio Santoro
Glioblastoma is a solid, infiltrating, and the most frequent highly malignant primary brain tumor. Our aim was to find the correlation between sex, age, preoperative Karnofsky performance status (KPS), presenting with seizures, and extent of resection (EOR) with overall survival (OS), progression-free survival (PFS), and postoperative KPS, along with the prognostic value of IDH1, MGMT, ATRX, EGFR, and TP53 genes mutations and of Ki67 through the analysis of a single-operator series in order to avoid the biases of a multi-operator series, such as the lack of homogeneity in surgical and adjuvant nonsurgical treatments...
February 9, 2020: Brain Sciences
https://read.qxmd.com/read/32028001/longitudinal-monitoring-of-gd-dtpa-following-convection-enhanced-delivery-in-the-brainstem
#36
Umberto Tosi, Mark M Souweidane
BACKGROUND: Convection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma (DIPG). Therapeutic benefit in part is predictably dependent upon drug distribution within tumor. However, therapeutics can rarely be detected through conventional imaging techniques. Co-infusion of the tracer Gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume (Vd), tumor coverage, and efflux during and after administration...
February 3, 2020: World Neurosurgery
https://read.qxmd.com/read/32025728/high-grade-gliomas-in-adolescents-and-young-adults-highlight-histomolecular-differences-from-their-adult-and-pediatric-counterparts
#37
Alexandre Roux, Johan Pallud, Raphaël Saffroy, Myriam Edjlali-Goujon, Marie-Anne Debily, Nathalie Boddaert, Marc Sanson, Stéphanie Puget, Steven Knafo, Clovis Adam, Thierry Faillot, Dominique Cazals-Hatem, Emmanuel Mandonnet, Marc Polivka, Georges Dorfmüller, Aurélie Dauta, Mathilde Desplanques, Albane Gareton, Mélanie Pages, Arnault Tauziede-Espariat, Jacques Grill, Franck Bourdeaut, François Doz, Frédéric Dhermain, Karima Mokhtari, Fabrice Chretien, Dominique Figarella-Branger, Pascale Varlet
BACKGROUND: Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). METHODS: We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI...
August 17, 2020: Neuro-oncology
https://read.qxmd.com/read/32016716/radiation-dose-response-of-neurologic-symptoms-during-conformal-radiotherapy-for-diffuse-intrinsic-pontine-glioma
#38
Christopher L Tinkle, Kristen Campbell, Yuanyuan Han, Yimei Li, Brandon Bianski, Alberto Broniscer, Raja B Khan, Thomas E Merchant
PURPOSE: To estimate the rate and magnitude of neurologic symptom change during radiation therapy (RT) and impact of symptom change on survival outcomes in patients with diffuse intrinsic pontine glioma (DIPG). METHODS: From 2006 to 2014, 108 patients with newly diagnosed DIPG were treated with conventionally fractionated radiation therapy (RT) to 54 Gy (median) at our institution. The presence and severity of neurologic symptoms related to cranial neuropathy (CN) and cerebellar (CB) and long-tract (LT) signs was reviewed before and weekly during RT for each patient...
February 3, 2020: Journal of Neuro-oncology
https://read.qxmd.com/read/32002312/impact-of-intravenous-vitamin-c-and-endolaser-therapies-on-a-pediatric-brainstem-glioma-case
#39
Ivette M Solís-Nolasco, Gilberto Caraballo, Michael J González, José Olalde, Raul H Morales-Borges
Pediatric cases of a brainstem glioma are one of the most difficult tumors to treat. In children, this type of cancer is perhaps the most dreaded of cancers due to its poor prognosis, yet it remains an area of intense research. In the case presented herein, conventional chemotherapy and radiotherapy treatments were not showing any improvement. The patient was then treated with high-dose intravenous vitamin C (IVC) and endolaser therapy. A significant reduction in glioma's size was achieved in 2 months with this adjunct therapy...
2020: Global Advances in Health and Medicine: Improving Healthcare Outcomes Worldwide
https://read.qxmd.com/read/31940975/combined-targeting-of-mutant-p53-and-jumonji-family-histone-demethylase-augments-therapeutic-efficacy-of-radiation-in-h3k27m-dipg
#40
Anatoly Nikolaev, John B Fiveash, Eddy S Yang
Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor with a 5-year survival of <1%. Up to 80% of the DIPG tumors contain a specific K27M mutation in one of the two genes encoding histone H3 (H3K27M). Furthermore, p53 mutations found in >70-80% of H3K27M DIPG, and mutant p53 status is associated with a decreased response to radiation treatment and worse overall prognosis. Recent evidence indicates that H3K27M mutation disrupts tri-methylation at H3K27 leading to aberrant gene expression...
January 13, 2020: International Journal of Molecular Sciences
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