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pontine glioma

Victor M Lu, John P Welby, Anita Mahajan, Nadia N Laack, David J Daniels
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a pediatric brain tumor with dismal prognosis despite initial radiation therapy (RT). The clinical consequences of attempting reirradiation (reRT) in these patients to alleviate both symptomatology and improve prognosis are currently unclear. Thus, the aim of this systematic review and meta-analysis was to clarify the efficacy and safety of reRT in DIPG. METHODS: Searches of seven electronic databases from inception to January 2019 were conducted following the appropriate guidelines...
March 16, 2019: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
John P Welby, Tatiana Kaptzan, Anton Wohl, Timothy E Peterson, Aditya Raghunathan, Desmond A Brown, Shiv K Gupta, Liang Zhang, David J Daniels
Diffuse Midline Gliomas with Histone 3-Lysine-27-Methionine (H3K27M) mutation constitute the majority of Diffuse Intrinsic Pontine Glioma (DIPG), which is the most aggressive form of pediatric glioma with a dire prognosis. DIPG are lethal tumors found in younger children with a median survival <1 year from diagnosis. Discovery of the characteristic H3K27M mutations offers opportunity and hope for development of targeted therapies for this deadly disease. The H3K27M mutation, likely through epigenetic alterations in specific H3 lysine trimethylation levels and subsequent gene expression, plays a significant role in pathogenesis of DIPG...
2019: Frontiers in Oncology
Sabine Mueller, Payal Jain, Winnie S Liang, Lindsay Kilburn, Cassie Kline, Nalin Gupta, Eshini Panditharatna, Suresh N Magge, Bo Zhang, Yuankun Zhu, John R Crawford, Anu Banerjee, Kellie Nazemi, Roger J Packer, Claudia K Petritsch, Nathalene Truffaux, Alison Roos, Sara Nasser, Joanna J Phillips, David Solomon, Annette Molinaro, Angela J Waanders, Sara A Byron, Michael E Berens, John Kuhn, Javad Nazarian, Michael Prados, Adam C Resnick
This clinical trial evaluated whether whole exome sequencing (WES) and RNA sequencing (RNAseq) of paired normal and tumor tissues could be incorporated into a personalized treatment plan for newly diagnosed patients (<25 years of age) with diffuse intrinsic pontine glioma (DIPG). Additionally, whole genome sequencing (WGS) was compared with WES to determine if WGS would further inform treatment decisions, and whether circulating tumor DNA (ctDNA) could detect the H3K27M mutation to allow assessment of therapy response...
March 12, 2019: International Journal of Cancer. Journal International du Cancer
Krishnamurthy Sridhar, K Srinivasan
No abstract text is available yet for this article.
January 2019: Neurology India
Andrew Deweyert, Erin Iredale, Hu Xu, Eugene Wong, Susanne Schmid, Matthew O Hebb
INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT). METHODS: DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system...
March 9, 2019: Journal of Neuro-oncology
Mwangala Precious Akamandisa, Kai Nie, Rita Nahta, Dolores Hambardzumyan, Robert Craig Castellino
BACKGROUND: Children with diffuse intrinsic pontine glioma (DIPG) succumb to disease within 2 years of diagnosis despite treatment with radiation (IR) and/or chemotherapy. Our aim was to determine the role of PPM1D mutation, present in up to 25% of cases, in DIPG pathogenesis and treatment. METHODS: Using genetic and pharmacologic approaches, we assayed effects of PPM1D mutation on DIPG growth and murine survival. We assayed effects of targeting mutated PPM1D alone or with IR on signaling, cell cycle, proliferation, and apoptosis in patient-derived DIPG cells in vitro, in organotypic brain slices, and in vivo...
March 10, 2019: Neuro-oncology
Umberto Tosi, Harikrishna Kommidi, Vanessa Bellat, Christopher S Marnell, Hua Guo, Oluwaseyi Adeuyan, Melanie E Schweitzer, Nandi Chen, Taojunfeng Su, Guoan Zhang, Uday B Maachani, David J Pisapia, Benedict Law, Mark M Souweidane, Richard Ting
The blood-brain barrier (BBB) represents a major obstacle in delivering therapeutics to brain lesions. Convection-enhanced delivery (CED), a method that bypasses the BBB through direct, cannula-mediated drug delivery, is one solution to maintaining increased, effective drug concentration at these lesions. CED was recently proven safe in a phase I clinical trial against diffuse intrinsic pontine glioma (DIPG), a childhood cancer. Unfortunately, the exact relationship between drug size, charge, and pharmacokinetic behavior in the brain parenchyma are difficult to observe in vivo...
March 6, 2019: ACS Chemical Neuroscience
Rafael Ceschin, Mehmet Kocak, Sridhar Vajapeyam, Ian F Pollack, Arzu Onar-Thomas, Ira J Dunkel, Tina Young Poussaint, Ashok Panigrahy
BACKGROUND AND PURPOSE: Baseline diffusion or apparent diffusion coefficient (ADC) characteristics have been shown to predict outcome related to DIPG, but the predictive value of post-radiation ADC is less well understood. ADC parametric mapping (FDM) was used to measure radiation-related changes in ADC and compared these metrics to baseline ADC in predicting progression-free survival and overall survival using a large multi-center cohort of DIPG patients (Pediatric Brain Tumor Consortium-PBTC)...
February 27, 2019: Journal of Neuro-oncology
Jaume Mora
No abstract text is available yet for this article.
2019: Frontiers in Oncology
Benjamin T Himes, Liang Zhang, David J Daniels
Diffuse midline gliomas harboring the H3 K27M mutation-including the previously named diffuse intrinsic pontine glioma (DIPG)-are lethal high-grade pediatric brain tumors that are inoperable and without cure. Despite numerous clinical trials, the prognosis remains poor, with a median survival of ~1 year from diagnosis. Systemic administration of chemotherapeutic agents is often hindered by the blood brain barrier (BBB), and even drugs that successfully cross the barrier may suffer from unpredictable distributions...
2019: Frontiers in Oncology
Constanze Buus-Gehrig, Thomas Lehrnbecher, Luciana Porto, Martina Becker, Thomas Freiman, Michel Mittelbronn, Konrad Bochennek
Tumors of the central nervous system represent the largest group of solid tumors found in pediatric patients. Pilocytic astrocytoma is the most common pediatric glioma, mostly located in the posterior fossa. The majority of brainstem tumors, however, are classified as highly aggressive diffuse intrinsic pontine gliomas (DIPGs) and their prognosis is dismal.The authors report on the case of a neonate in whom MRI and neuropathological assessment were used to diagnose DIPG. Before initiation of the planned chemotherapy, the tumor regressed spontaneously, and the newborn exhibited a normal neurological development...
February 15, 2019: Journal of Neurosurgery. Pediatrics
André B Silveira, Lawryn H Kasper, Yiping Fan, Hongjian Jin, Gang Wu, Timothy I Shaw, Xiaoyan Zhu, Jon D Larson, John Easton, Ying Shao, Donald A Yergeau, Celeste Rosencrance, Kristy Boggs, Michael C Rusch, Liang Ding, Junyuan Zhang, David Finkelstein, Rachel M Noyes, Brent L Russell, Beisi Xu, Alberto Broniscer, Cynthia Wetmore, Stanley B Pounds, David W Ellison, Jinghui Zhang, Suzanne J Baker
Histone H3 K27M mutation is the defining molecular feature of the devastating pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). The prevalence of histone H3 K27M mutations indicates a critical role in DIPGs, but the contribution of the mutation to disease pathogenesis remains unclear. We show that knockdown of this mutation in DIPG xenografts restores K27M-dependent loss of H3K27me3 and delays tumor growth. Comparisons of matched DIPG xenografts with and without K27M knockdown allowed identification of mutation-specific effects on the transcriptome and epigenome...
February 15, 2019: Acta Neuropathologica
Chloé Louise Gelder, Cynthia Hawkins, Michal Zapotocky, Peter Dirks, Ute Bartels, Eric Bouffet
Dissemination of diffuse intrinsic pontine glioma (DIPG) outside the central nervous system is exceptional. Here, we present a child diagnosed with DIPG who developed seeding along the track of the ventriculoperitoneal shunt and review the literature on this unusual occurrence.
January 31, 2019: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Tina Huang, Roxanna Garcia, Jin Qi, Rishi Lulla, Craig Horbinski, Amir Behdad, Nitin Wadhwani, Ali Shilatifard, Charles James, Amanda Saratsis
Pediatric diffuse midline glioma is a highly morbid glial neoplasm that may arise in the thalamus or brainstem (also known as diffuse intrinsic pontine glioma or DIPG). Because tumor anatomic location precludes surgical resection, diagnosis and treatment is based on MR imaging and analysis of biopsy specimens. Up to 80% of pediatric diffuse midline gliomas harbor a histone H3 mutation resulting in the replacement of lysine 27 with methionine (K27M) in genes encoding histone H3 variant H3.3 ( H3F3A ) or H3.1 ( HIST1H3B )...
December 14, 2018: Oncotarget
Yu Sun, Cheng Xu, Changcun Pan, Xin Chen, Yibo Geng, Yuliang Wu, Peng Zhang, Wenhao Wu, Yu Wang, Deling Li, Zhen Wu, Junting Zhang, Qiaoran Xi, Liwei Zhang
Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG...
January 3, 2019: Neuroscience Bulletin
Lelio Guida, Frank-Emmanuel Roux, Maura Massimino, Carlo E Marras, Erik Sganzerla, Carlo Giussani
OBJECT: Diffuse Intrinsic Pontine Gliomas (DIPG) related hydrocephalus occurs as the result of tumor growth and Aqueduct obstruction. There is no consensus about the best surgical option, thus a review has been performed to clarify the rate of success, complications and possible issues of Endoscopic Third Ventriculostomy (ETV) in comparison to the other available techniques. METHODS: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and it was registered with the PROSPERO International Prospective Register of Systematic Reviews(CRD42018089001)...
December 29, 2018: World Neurosurgery
Jon D Larson, Lawryn H Kasper, Barbara S Paugh, Hongjian Jin, Gang Wu, Chang-Hyuk Kwon, Yiping Fan, Timothy I Shaw, André B Silveira, Chunxu Qu, Raymond Xu, Xiaoyan Zhu, Junyuan Zhang, Helen R Russell, Jennifer L Peters, David Finkelstein, Beisi Xu, Tong Lin, Christopher L Tinkle, Zoltan Patay, Arzu Onar-Thomas, Stanley B Pounds, Peter J McKinnon, David W Ellison, Jinghui Zhang, Suzanne J Baker
Diffuse intrinsic pontine gliomas (DIPGs) are incurable childhood brainstem tumors with frequent histone H3 K27M mutations and recurrent alterations in PDGFRA and TP53. We generated genetically engineered inducible mice and showed that H3.3 K27M enhanced neural stem cell self-renewal while preserving regional identity. Neonatal induction of H3.3 K27M cooperated with activating platelet-derived growth factor receptor α (PDGFRα) mutant and Trp53 loss to accelerate development of diffuse brainstem gliomas that recapitulated human DIPG gene expression signatures and showed global changes in H3K27 posttranslational modifications, but relatively restricted gene expression changes...
December 11, 2018: Cancer Cell
Peter F Morgenstern, Zhiping Zhou, Eva Wembacher-Schröder, Vincent Cina, Apostolos John Tsiouris, Mark M Souweidane
OBJECTIVEConvection-enhanced delivery (CED) has been explored as a therapeutic strategy for diffuse intrinsic pontine glioma (DIPG). Variables that may affect tolerance include infusate volume, infusion rate, catheter trajectory, and target position. Supratentorial approaches for catheter placement and infusate distribution patterns may conflict with corticospinal tracts (CSTs). The clinical relevance of these anatomical constraints has not been described. The authors report their experience using CED in the brainstem as it relates to anatomical CST conflict and association with clinical tolerance...
December 21, 2018: Journal of Neurosurgery
Victor M Lu, Mohammed A Alvi, Kerrie L McDonald, David J Daniels
OBJECTIVEPediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma, present a prognostic challenge given their lethality and rarity. A substitution mutation of lysine for methionine at position 27 in histone H3 (H3K27M) has been shown to be highly specific to these tumors. Data are accumulating regarding the poor outcomes of patients with these tumors; however, the quantification of pooled outcomes has yet to be done, which could assist in prioritizing management. The aim of this study was to quantitatively pool data in the current literature on the H3K27M mutation as an independent prognostic factor in pHGG...
November 1, 2018: Journal of Neurosurgery. Pediatrics
John D Heiss, Aria Jamshidi, Smit Shah, Staci Martin, Pamela L Wolters, Davis P Argersinger, Katherine E Warren, Russell R Lonser
OBJECTIVEIn this clinical trial report, the authors analyze safety and infusion distribution of IL13-Pseudomonas exotoxin, an antitumor chimeric molecule, administered via intratumoral convection enhanced delivery (CED) in pediatric patients with diffuse intrinsic pontine glioma (DIPG).METHODSThis was a Phase I single-institution, open-label, dose-escalation, safety and tolerability study of IL13-PE38QQR infused via single-catheter CED into 5 pediatric DIPG patients. IL13-PE38QQR was administered to regions of tumor selected by radiographic findings...
December 1, 2018: Journal of Neurosurgery. Pediatrics
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