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https://www.readbyqxmd.com/read/28686124/influence-of-an-intratumoral-cyst-on-drug-distribution-by-convection-enhanced-delivery-case-report
#1
Iryna Ivasyk, Peter F Morgenstern, Eva Wembacher-Schroeder, Mark M Souweidane
Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. The patient was treated according to protocol with CED of (124)I-8H9 to the pons for nonprogressive DIPG after radiation therapy as part of a Phase I trial (clinical trial registration no...
July 7, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28643992/recent-perspectives-of-molecular-aberrations-in-pediatric-high-grade-glioma
#2
Zhengwei Li, Qingzeng Sun, Yingchun Shi
Paediatric high-grade glioma (HGG), including diffuse intrinsic pontine glioma (DIPG) are highly aggressive tumours with no effective cures. Lack of understanding of the molecular biology of these tumours, in part due to lack of well-characterized pre-clinical models, is a great challenge in the development of novel therapies. Recent studies have shown that paediatric HGG short-term cell cultures retain many of the tumour characteristics in vivo and at present one of the best choices for in-vivo experimental studies...
June 22, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28592748/epigenetic-targeted-therapy-for-diffuse-intrinsic-pontine-glioma
#3
Rintaro Hashizume
Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5-7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone...
June 7, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28591729/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#4
Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B Stevenson, Maryam Fouladi, Rachid Drissi
Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587626/evaluation-of-a-novel-antibody-to-define-histone-3-3-g34r-mutant-brain-tumours
#5
Farhana Haque, Pascale Varlet, Julien Puntonet, Lisa Storer, Aikaterini Bountali, Ruman Rahman, Jacques Grill, Angel M Carcaboso, Chris Jones, Robert Layfield, Richard G Grundy
Missense somatic mutations affecting histone H3.1 and H3.3 proteins are now accepted as the hallmark of paediatric diffuse intrinsic pontine gliomas (DIPG), non-brain stem paediatric high grade gliomas (pHGG) as well as a subset of adult glioblastoma multiforme (GBM). Different mutations give rise to one of three amino acid substitutions at two critical positions within the histone tails, K27M, G34R/V. Several studies have highlighted gene expression and epigenetic changes associated with histone H3 mutations; however their precise roles in tumourigenesis remain incompletely understood...
June 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28582410/a-phase-i-study-of-single-agent-perifosine-for-recurrent-or-refractory-pediatric-cns-and-solid-tumors
#6
Oren J Becher, Nathan E Millard, Shakeel Modak, Brian H Kushner, Sofia Haque, Ivan Spasojevic, Tanya M Trippett, Stephen W Gilheeney, Yasmin Khakoo, David C Lyden, Kevin C De Braganca, Jill M Kolesar, Jason T Huse, Kim Kramer, Nai-Kong V Cheung, Ira J Dunkel
The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4-18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3]), neuroblastoma (n = 8), Wilms tumor (n = 1), and Ewing sarcoma (n = 1) were treated...
2017: PloS One
https://www.readbyqxmd.com/read/28566437/local-dna-repair-inhibition-for-sustained-radiosensitization-in-high-grade-gliomas
#7
Amanda R King, Christopher D Corso, Evan M Chen, Eric Song, Paul Bongiorni, Zhe Chen, Ranjini K Sundaram, Ranjit S Bindra, W Mark Saltzman
High-grade gliomas such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) are characterized by an aggressive phenotype with nearly universal local disease progression despite multimodal treatment, which typically includes chemotherapy, radiation therapy (RT), and possibly surgery. Radiosensitizers that have improved the effects of RT for extracranial tumors have been ineffective for the treatment of GBM and DIPG, in part due to poor blood brain barrier penetration and rapid intracranial clearance of small molecules...
May 31, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28560664/external-validation-of-the-diffuse-intrinsic-pontine-glioma-survival-prediction-model-a-collaborative-report-from-the-international-dipg-registry-and-the-siope-dipg-registry
#8
Sophie E M Veldhuijzen van Zanten, Adam Lane, Martijn W Heymans, Joshua Baugh, Brooklyn Chaney, Lindsey M Hoffman, Renee Doughman, Marc H A Jansen, Esther Sanchez, William P Vandertop, Gertjan J L Kaspers, Dannis G van Vuurden, Maryam Fouladi, Blaise V Jones, James Leach
We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities...
May 30, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28547002/oncolytic-herpes-simplex-virus-inhibits-pediatric-brain-tumor-migration-and-invasion
#9
Julia V Cockle, Anke Brüning-Richardson, Karen J Scott, Jill Thompson, Timothy Kottke, Ewan Morrison, Azam Ismail, Angel M Carcaboso, Ailsa Rose, Peter Selby, Joe Conner, Susan Picton, Susan Short, Richard Vile, Alan Melcher, Elizabeth Ilett
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action: the inhibition of migration and invasion in pediatric brain tumors. We evaluated the effect of oncolytic herpes simplex virus 1716 (HSV1716) on the migration and invasion of pHGG and DIPG both in vitro using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays and in vivo using an orthotopic xenograft model of DIPG invasion...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28544128/a-pediatric-trial-of-radiation-cetuximab-followed-by-irinotecan-cetuximab-in-newly-diagnosed-diffuse-pontine-gliomas-and-high-grade-astrocytomas-a-pediatric-oncology-experimental-therapeutics-investigators-consortium-study
#10
Margaret E Macy, Mark W Kieran, Susan N Chi, Kenneth J Cohen, Tobey J MacDonald, Amy A Smith, Michael M Etzl, Michele C Kuei, Andrew M Donson, Lia Gore, Jennifer DiRenzo, Tanya M Trippett, Irina Ostrovnaya, Aru Narendran, Nicholas K Foreman, Ira J Dunkel
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. METHODS: Eligible patients of age 3-21 years had newly diagnosed DIPG or HGA...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28542253/repurposing-the-anti-epileptic-drug-sodium-valproate-as-an-adjuvant-treatment-for-diffuse-intrinsic-pontine-glioma
#11
Clare L Killick-Cole, William G B Singleton, Alison S Bienemann, Daniel J Asby, Marcella J Wyatt, Lisa J Boulter, Neil U Barua, Steven S Gill
Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#12
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date, the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28486100/using-epigenetic-reprogramming-to-treat-pediatric-brain-cancer
#13
Milan G Chheda, David H Gutmann
In this issue of Cancer Cell, Nagaraja et al. dissect the molecular mechanisms underlying therapeutic responses to transcriptional disruptors in the fatal pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). Moreover, they identify super-enhancers mediating these effects, highlighting how normal brain developmental programs can be hijacked in cancer.
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28455397/targeting-cdk7-or-brd4-blocks-diffuse-intrinsic-pontine-glioma-growth
#14
(no author information available yet)
Diffuse intrinsic pontine glioma (DIPG) is sensitive to transcriptional disruption via CDK7/BRD4 blockade.
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28450157/the-dual-mtor-kinase-inhibitor-tak228-inhibits-tumorigenicity-and-enhances-radiosensitization-in-diffuse-intrinsic-pontine-glioma
#15
Hiroaki Miyahara, Sridevi Yadavilli, Manabu Natsumeda, Jeffrey A Rubens, Louis Rodgers, Madhuri Kambhampati, Isabella C Taylor, Harpreet Kaur, Laura Asnaghi, Charles G Eberhart, Katherine E Warren, Javad Nazarian, Eric H Raabe
Diffuse intrinsic pontine glioma (DIPG) is an invasive and treatment-refractory pediatric brain tumor. Primary DIPG tumors harbor a number of mutations including alterations in PTEN, AKT, and PI3K and exhibit activation of mammalian Target of Rapamycin Complex 1 and 2 (mTORC1/2). mTORC1/2 regulate protein translation, cell growth, survival, invasion, and metabolism. Pharmacological inhibition of mTORC1 is minimally effective in DIPG. However, the activity of dual TORC kinase inhibitors has not been examined in this tumor type...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28434841/transcriptional-dependencies-in-diffuse-intrinsic-pontine-glioma
#16
Surya Nagaraja, Nicholas A Vitanza, Pamelyn J Woo, Kathryn R Taylor, Fang Liu, Lei Zhang, Meng Li, Wei Meng, Anitha Ponnuswami, Wenchao Sun, Jie Ma, Esther Hulleman, Tomek Swigut, Joanna Wysocka, Yujie Tang, Michelle Monje
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28416018/detection-of-histone-h3-mutations-in-cerebrospinal-fluid-derived-tumor-dna-from-children-with-diffuse-midline-glioma
#17
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
#18
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/28373034/topical-delivery-of-anthramycin-i-influence-of-neat-solvents
#19
Tasnuva Haque, Khondaker M Rahman, David E Thurston, Jonathan Hadgraft, Majella E Lane
Anthramycin (ANT) was the first pyrrolobenzodiazepine (PBD) molecule to be isolated, and is a potent cytotoxic agent. Although the PBD family has been investigated for use in systemic chemotherapy, their application in the management of actinic keratoses (AK) or skin cancer has not been investigated to date. In the present work, anthramycin (ANT) was selected as a model PBD compound, and the skin penetration of the molecule was investigated using conventional Franz diffusion cells. Finite dose permeation studies of ANT were performed using propylene glycol (PG), 1,3-butanediol (BD), dipropylene glycol (DiPG), Transcutol P® (TC), propylene glycol monocaprylate (PGMC), propylene glycol monolaurate (PGML) and isopropyl myristate (IPM)...
June 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28371920/diffuse-intrinsic-pontine-gliomas-current-management-and-new-biologic-insights-is-there-a-glimmer-of-hope
#20
Kenneth J Cohen, Nada Jabado, Jacques Grill
Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor...
March 24, 2017: Neuro-oncology
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