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https://www.readbyqxmd.com/read/28416018/detection-of-histone-h3-mutations-in-cerebrospinal-fluid-derived-tumor-dna-from-children-with-diffuse-midline-glioma
#1
Tina Y Huang, Andrea Piunti, Rishi R Lulla, Jin Qi, Craig M Horbinski, Tadanori Tomita, C David James, Ali Shilatifard, Amanda M Saratsis
Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are highly morbid glial neoplasms of the thalamus or brainstem that typically arise in young children and are not surgically resectable. These tumors are characterized by a high rate of histone H3 mutation, resulting in replacement of lysine 27 with methionine (K27M) in genes encoding H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B). Detection of these gain-of-function mutations has clinical utility, as they are associated with distinct tumor biology and clinical outcomes...
April 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28401062/genomic-insights-into-diffuse-intrinsic-pontine-glioma
#2
REVIEW
Danielle H Lapin, Maria Tsoli, David S Ziegler
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor with a peak incidence in middle childhood and a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of over 250 clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care. The traditional practice to not biopsy DIPG led to a scarcity in available tissue samples for laboratory analysis that till recently hindered therapeutic advances...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28395412/-thinking-on-the-management-of-brainstem-gliomas-in-the-era-of-precision-medicine
#3
L W Zhang
No abstract text is available yet for this article.
April 4, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28362421/a-protocol-for-rapid-post-mortem-cell-culture-of-diffuse-intrinsic-pontine-glioma-dipg
#4
Grant L Lin, Michelle Monje
Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brainstem tumor that carries a universally fatal prognosis. Because surgical resection is not a viable treatment strategy and biopsy is not routinely performed, the availability of patient samples for research is limited. Consequently, efforts to study this disease have been challenged by a paucity of faithful disease models. To address this need, we describe here a protocol for the rapid processing of post-mortem autopsy tissue samples in order to generate durable patient-derived cell culture models that can be used in in vitro assays or in vivo orthotopic xenograft experiments...
March 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28339768/the-transcription-factor-olig2-is-important-for-the-biology-of-diffuse-intrinsic-pontine-gliomas
#5
Jane L Anderson, Ranjithmenon Muraleedharan, Nicole Oatman, Amanda Klotter, Satarupa Sengupta, Ronald R Waclaw, Jianqiang Wu, Rachid Drissi, Lili Miles, Eric H Raabe, Matthew L Weirauch, Maryam Fouladi, Lionel M Chow, Lindsey Hoffman, Mariko DeWire, Biplab Dasgupta
Background.: Diffuse intrinsic pontine glioma (DIPG) is a high-grade brainstem glioma of children with dismal prognosis. There is no single unifying model about the cell of origin of DIPGs. Proliferating cells in the developing human and mouse pons, the site of DIPGs, express neural stem/progenitor cell (NPC) markers, including Sox2, nestin, vimentin, Olig2, and glial fibrillary acidic protein, in an overlapping and non-overlapping manner, suggesting progenitor cell heterogeneity in the pons...
February 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28330960/a-multi-institutional-study-of-brainstem-gliomas-in-children-with-neurofibromatosis-type-1
#6
Jasia Mahdi, Amish C Shah, Aimee Sato, Stephanie M Morris, Robert C McKinstry, Robert Listernick, Roger J Packer, Michael J Fisher, David H Gutmann
OBJECTIVE: To define the clinical and radiologic features of brainstem gliomas (BSGs) in children with neurofibromatosis type 1 (NF1). METHODS: We performed a retrospective cross-sectional study of 133 children with NF1 and concurrent BSGs cared for at 4 NF1 referral centers. BSG was determined using radiographic criteria. Age at diagnosis, tumor location and appearance, clinical symptoms, treatment, and presence of a concurrent optic pathway glioma were assessed...
March 22, 2017: Neurology
https://www.readbyqxmd.com/read/28291423/preclinical-evaluation-of-convection-enhanced-delivery-of-liposomal-doxorubicin-to-treat-pediatric-diffuse-intrinsic-pontine-glioma-and-thalamic-high-grade-glioma
#7
A Charlotte P Sewing, Tonny Lagerweij, Dannis G van Vuurden, Michaël H Meel, Susanna J E Veringa, Angel M Carcaboso, Pieter J Gaillard, W Peter Vandertop, Pieter Wesseling, David Noske, Gertjan J L Kaspers, Esther Hulleman
OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models...
February 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28263307/therapeutic-targeting-of-polycomb-and-bet-bromodomain-proteins-in-diffuse-intrinsic-pontine-gliomas
#8
Andrea Piunti, Rintaro Hashizume, Marc A Morgan, Elizabeth T Bartom, Craig M Horbinski, Stacy A Marshall, Emily J Rendleman, Quanhong Ma, Yoh-Hei Takahashi, Ashley R Woodfin, Alexander V Misharin, Nebiyu A Abshiru, Rishi R Lulla, Amanda M Saratsis, Neil L Kelleher, C David James, Ali Shilatifard
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor characterized by rapid and uniform patient demise. A heterozygous point mutation of histone H3 occurs in more than 80% of these tumors and results in a lysine-to-methionine substitution (H3K27M). Expression of this histone mutant is accompanied by a reduction in the levels of polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation (H3K27me3), and this is hypothesized to be a driving event of DIPG oncogenesis...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28236065/glioblastoma-spheroids-produce-infiltrative-gliomas-in-the-rat-brainstem
#9
Zhiping Zhou, Neal Luther, Ranjodh Singh, John A Boockvar, Mark M Souweidane, Jeffrey P Greenfield
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is universally fatal without proven therapy other than radiation therapy for palliation. Representative animal models will play an essential role in the preclinical stage of future therapy development. To address the shortage of representative models, we created a novel infiltrative brainstem glioma model in rats based on glioblastoma spheroids. METHODS: Cells dissociated from glioblastoma spheroids grown from surgical specimens were implanted into the brainstem of NIH nude rats...
March 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28178670/new-in-vivo-avatars-of-diffuse-intrinsic-pontine-gliomas-dipg-from-stereotactic-biopsies-performed-at-diagnosis
#10
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...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28163514/pilocytic-midbrain-astrocytoma-presenting-with-fresh-bleed-after-twenty-one-years-survival-following-first-surgery-a-unique-case-of-longest-brainstem-glioma-survival
#11
Guru Dutta Satyarthee, M D Sudhan, V S Mehta
Brainstem glioma usually carries a poor prognosis and prolonged survival is very infrequent. In a detailed Pubmed, Medline search for prolonged survival, authors could got a longest survival only up to seventeen years, reported by Umehara et al, who was subjected to gamma knife therapy and got symptomatic, MRI brain reveled large tumor growth during pregnancy necessitating emergency surgery and histopathological diagnosis was pilocytic astrocytoma. Authors report an interesting case of midbrain glioma diagnosed 21 years back, who underwent gross resection in the year 1993, histopathology was pilocytic astrocytoma, WHO grade I, and received gamma knife surgery for residual subsequently and he presented with sudden onset left sided hemiplegia on the current admission...
December 2016: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/28156189/feline-glioma-a-retrospective-study-and-review-of-the-literature
#12
Daniel R Rissi, Andrew D Miller
Case series summary This study aimed to evaluate the pathologic and diagnostic features of 13 cases of feline glioma diagnosed at two veterinary diagnostic institutions over 16 years. A retrospective search was conducted using the laboratory information system. Selected cases were reviewed, tumors were classified according to the 2007 World Health Organization Classification of Tumours of the Central Nervous System, and tissue sections were submitted to an immunohistochemistry panel for further characterization...
February 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28108511/biomarker-based-pet-imaging-of-diffuse-intrinsic-pontine-glioma-in-mouse-models
#13
Susanne Kossatz, Brandon Carney, Melanie Schweitzer, Giuseppe Carlucci, Vesselin Z Miloushev, Uday B Maachani, Prajwal Rajappa, Kayvan R Keshari, David Pisapia, Wolfgang A Weber, Mark M Souweidane, Thomas Reiner
Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize a positron emission tomography (PET) probe for imaging DIPG in vivo In human histological tissues, the probes target, PARP1, was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model, and probe uptake correlated to histologically determined tumor infiltration. Imaging with the sister fluorescence agent revealed that uptake was confined to proliferating, PARP1-expressing cells...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28052119/pre-clinical-study-of-panobinostat-in-xenograft-and-genetically-engineered-murine-diffuse-intrinsic-pontine-glioma-models
#14
Tammy Hennika, Guo Hu, Nagore G Olaciregui, Kelly L Barton, Anahid Ehteda, Arjanna Chitranjan, Cecilia Chang, Andrew J Gifford, Maria Tsoli, David S Ziegler, Angel M Carcaboso, Oren J Becher
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG), or high-grade brainstem glioma (BSG), is one of the major causes of brain tumor-related deaths in children. Its prognosis has remained poor despite numerous efforts to improve survival. Panobinostat, a histone deacetylase inhibitor, is a targeted agent that has recently shown pre-clinical efficacy and entered a phase I clinical trial for the treatment of children with recurrent or progressive DIPG. METHODS: A collaborative pre-clinical study was conducted using both a genetic BSG mouse model driven by PDGF-B signaling, p53 loss, and ectopic H3...
2017: PloS One
https://www.readbyqxmd.com/read/28048352/th-ef-brb-01-best-in-physics-therapy-dosimetric-comparison-of-4%C3%AF-and-clinical-imrt-for-cortex-sparing-high-grade-glioma-treatment
#15
K Woods, R Karunamuni, A Tran, V Yu, D Nguyen, J Hattangadi-Gluth, K Sheng
PURPOSE: Thinning of the cerebral cortex has been observed in patients treated with fractionated partial brain radiation therapy and may contribute to cognitive decline following treatment. The extent of this thinning is dose-dependent, and was shown comparable to that of neurodegenerative diseases such as Alzheimer's disease at one year post-therapy. This study investigates whether 4π radiotherapy can enable better sparing of the cortex and other critical structures when compared to conventional clinical IMRT plans...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28039366/the-use-of-o-2-18f-fluoroethyl-l-tyrosine-pet-in-the-diagnosis-of-gliomas-located-in-the-brainstem-and-spinal-cord
#16
Caroline Tscherpel, Veronika Dunkl, Garry Ceccon, Gabriele Stoffels, Natalie Judov, Marion Rapp, Philipp T Meyer, Elena Rota Kops, Johannes Ermert, Gereon R Fink, Nadim J Shah, Karl-Josef Langen, Norbert Galldiks
BACKGROUND: Despite an increasing number of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET studies in supratentorial gliomas, studies regarding the usefulness of (18)F-FET PET in brainstem and spinal cord gliomas to date remain scarce. METHODS: Thirty-six (18)F-FET PET scans were performed in 29 patients with brainstem (n = 29 scans) or spinal cord glioma (n = 7 scans). In 32 of 36 PET scans, a dynamic acquisition was performed. Fifteen scans in 15 patients were performed to assess newly diagnosed lesions, and 21 scans were obtained during follow-up: for diagnosing tumor progression (n = 15 scans in 14 patients) as well as for treatment monitoring (n = 6 scans in 3 patients)...
December 29, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28032389/bithalamic-gliomas-may-be-molecularly-distinct-from-their-unilateral-high-grade-counterparts
#17
Alberto Broniscer, Scott N Hwang, Omar Chamdine, Tong Lin, Stanley Pounds, Arzu Onar-Thomas, Lei Chi, Sheila Shurtleff, Sariah Allen, Amar Gajjar, Paul Northcott, Brent A Orr
Bithalamic gliomas are rare cancers diagnosed based on poorly defined radiologic criteria. Infiltrative astrocytomas account for most cases. While some previous studies reported dismal outcomes for patients with bithalamic gliomas irrespective of therapy and histologic grade, others described better prognoses even without anticancer therapy. Little is known about their molecular characteristics. We reviewed clinical, radiologic, and histologic features of patients with bithalamic gliomas treated at our institution over 15 years...
December 28, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27987035/distant-recurrences-limit-the-survival-of-patients-with-thalamic-high-grade-gliomas-after-successful-resection
#18
Ryuta Saito, Toshihiro Kumabe, Masayuki Kanamori, Yukihiko Sonoda, Teiji Tominaga
The indications of surgery for thalamic high-grade gliomas are not well established. The present study investigated the outcome of 21 patients treated by surgery and reports the high incidence of distant recurrences including disseminations after successful removal. Twenty-one patients with thalamic high-grade gliomas not invading the pyramidal tract or midbrain underwent cytoreductive surgery at our institute from June 1997 to August 2015. Surgery was performed with the aid of a neuronavigation system, electrophysiological monitoring, and fluorescence navigation...
December 17, 2016: Neurosurgical Review
https://www.readbyqxmd.com/read/27889018/posterior-fossa-tumors
#19
REVIEW
Lara A Brandão, Tina Young Poussaint
Pediatric brain tumors are the leading cause of death from solid tumors in childhood. The most common posterior fossa tumors in children are medulloblastoma, atypical teratoid/rhabdoid tumor, cerebellar pilocytic astrocytoma, ependymoma, and brainstem glioma. Location, and imaging findings on computed tomography (CT) and conventional MR (cMR) imaging may provide important clues to the most likely diagnosis. Moreover, information obtained from advanced MR imaging techniques increase diagnostic confidence and help distinguish between different histologic tumor types...
February 2017: Neuroimaging Clinics of North America
https://www.readbyqxmd.com/read/27810966/brainstem-low-grade-gliomas-in-children-excellent-outcomes-with-multimodality-therapy
#20
Santhosh A Upadhyaya, Carl Koschmann, Karin Muraszko, Sriram Venneti, Hugh J Garton, Daniel A Hamstra, Cormac O Maher, Bryan L Betz, Noah A Brown, Daniel Wahl, Helmut C Weigelin, Kathleen E DuRoss, Annette S Leonard, Patricia L Robertson
Safe maximal surgical resection is the initial treatment of choice for pediatric brainstem low-grade gliomas. Optimal therapy for incompletely resected tumors or that progress after surgery is uncertain. We reviewed the clinical characteristics, therapy, and outcomes of all children with nontectal brainstem low-grade gliomas treated at the University of Michigan between 1993 and 2013. Median age at diagnosis was 6 years; histology was confirmed in 23 of 25 tumors, 64% were pilocytic astrocytoma. Nineteen patients underwent initial tumor resection; 14/19 received no upfront adjuvant therapy...
November 3, 2016: Journal of Child Neurology
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