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Diffuse intrinsic pontine

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https://www.readbyqxmd.com/read/29456798/-18-f-radiolabeled-panobinostat-allows-for-positron-emission-tomography-guided-delivery-of-a-histone-deacetylase-inhibitor
#1
Harikrishna Kommidi, Umberto Tosi, Uday B Maachani, Hua Guo, Christopher S Marnell, Benedict Law, Mark M Souweidane, Richard Ting
Histone deacetylase (HDAC) inhibition is becoming an increasingly popular approach to treat cancer, as HDAC overexpression is common in many malignancies. The blood-brain barrier (BBB) prevents systemically delivered drugs from reaching brain at effective concentration, making small-molecule-HDAC inhibition in brain tumors particularly challenging. To circumvent the BBB, novel routes for administering therapeutics are being considered in the clinic, and a need exists for drugs whose deliveries can be directly imaged, so that effective delivery across the BBB can be monitored...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29435175/rest-upregulates-gremlin-to-modulate-diffuse-intrinsic-pontine-glioma-vasculature
#2
Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Keri Callegari, Rishi R Lulla, Stewart Goldman, Javad Nazarian, Veena Rajaram, Jason Fangusaro, Vidya Gopalakrishnan
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397521/end-of-life-care-of-children-with-diffuse-intrinsic-pontine-glioma
#3
Fyeza Hasan, Kevin Weingarten, Adam Rapoport, Eric Bouffet, Ute Bartels
The end-of-life management of children with diffuse intrinsic pontine glioma (DIPG) is challenging. Families cope with debilitating symptoms and make complex decisions regarding their child's care. However, there is little evidence guiding palliative care provision for these children. Our objective was to describe the dying trajectory of children with DIPG, their symptoms, the care they require and the end-of-life decisions made for them. This retrospective cohort study analyzed the end-of-life care of 41 consecutive patients with DIPG who died between January 2001 and June 2010...
February 3, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29393845/h3-k27m-mutant-gliomas-in-adults-vs-children-share-similar-histological-features-and-adverse-prognosis
#4
Bette K Kleinschmidt-DeMasters, Jean M Mulcahy Levy
BACKGROUND: H3 K27M mutation was originally described in pediatric diffuse intrinsic pontine gliomas (DIPGs), but has been recently recognized to occur also in adult midline diffuse gliomas, as well as midline tumors with other morphologies, including gangliogliomas (GGs), anaplastic GGs, pilocytic astrocytomas (PAs), and posterior fossa ependymomas. In a few patients with H3 K27M-mutant tumors with these alternate morphologies, longer survival has been reported, making grading difficult for the neuropathologist...
February 2, 2018: Clinical Neuropathology
https://www.readbyqxmd.com/read/29393184/chemotherapy-of-intracranial-gliomas-in-children
#5
Keita Terashima
Under specific indications, chemotherapy may play an important role in the treatment of pediatric patients with intracranial gliomas. It can be effectively administered in inoperable low-grade tumors, particularly with the use of combination regimens based on carboplatin and vincristine. In very young children with high-grade gliomas (HGG), chemotherapy may result in control of tumor growth, which allows to postpone fractionated radiation therapy (FRT). At the same time, in difference with adults, there is no current evidence that addition of chemotherapy to aggressive surgical resection followed by FRT has any positive impact on survival of pediatric patients with non-pontine HGG...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29369515/reirradiation-in-patients-with-diffuse-intrinsic-pontine-gliomas-the-canadian-experience
#6
Alvaro Lassaletta, Douglas Strother, Normand Laperriere, Juliette Hukin, Magimairajan Issai Vanan, Karen Goddard, Lucie Lafay-Cousin, Donna L Johnston, Shayna Zelcer, Michal Zapotocky, Revathi Rajagopal, Vijay Ramaswamy, Cynthia Hawkins, Uri Tabori, Annie Huang, Ute Bartels, Eric Bouffet
OBJECTIVE: Clinical trials have failed to demonstrate a survival benefit of adjuvant chemotherapy in diffuse intrinsic pontine gliomas (DIPG). Radiation therapy (RT) is the only effective treatment thus far and reirradiation (rRT) has become an option at the time of progression. The aim of this study was to review the Canadian experience of DIPG rRT with a focus on the safety and possible efficacy of this approach. METHOD: We retrospectively reviewed the demographic, clinical, and RT data of patients with DIPG treated in Canada with rRT...
January 25, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29367943/using-cystine-knot-proteins-as-a-novel-approach-to-retarget-oncolytic-measles-virus
#7
Sangeet Lal, Corey Raffel
Modified measles virus (MV) has effective oncolytic activity preclinically and is currently being investigated in clinical trials for various types of cancer. We investigated the use of cystine knot proteins (CKPs) to direct MV activity. CKPs are short polypeptides that bind their targets with high affinity. We used a CKP that binds αvβ3, αvβ5, and α5β1 integrins with single-digit nanomolar affinity to retarget MV to the integrins (MV-CKPint). MV-CKPint infected, replicated in, and killed human glioblastoma, medulloblastoma, diffuse intrinsic pontine glioma (DIPG), and melanoma cancer cells in vitro, all of which express the target integrins...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29364085/characterization-of-diffuse-intrinsic-pontine-glioma-radiosensitivity-using-synchrotron-microbeam-radiotherapy-and-conventional-radiation-therapy-in-vitro
#8
L M Smyth, P A W Rogers, J C Crosbie, J F Donoghue
Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy modality that has been proposed as an alternative to conventional radiation therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a devastating pediatric tumor of the brainstem. The primary goal of this study was to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761 and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that these DIPG cell lines would exhibit differential responses to each radiation modality...
February 2018: Radiation Research
https://www.readbyqxmd.com/read/29244086/cerebral-blood-flow-changes-after-radiation-therapy-identifies-pseudo-progression-in-diffuse-intrinsic-pontine-gliomas
#9
Raphael Calmon, Stephanie Puget, Pascale Varlet, Volodia Dangouloff-Ros, Thomas Blauwblomme, Kevin Beccaria, David Grevent, Christian Sainte-Rose, David Castel, Marie-Anne Debily, Christelle Dufour, Stéphanie Bolle, Frederic Dhermain, Ana Saitovitch, Monica Zilbovicius, Francis Brunelle, Jacques Grill, Nathalie Boddaert
Background: The interval between progression and death in diffuse intrinsic pontine glioma (DIPG) is usually < 6 months. However, reports of longer patient survival following radiotherapy, in the presence of radiological signs of progression, suggest that these cases may be comparable to pseudo-progression observed in adult glioblastoma. Our aim was to identify such cases and compare their multimodal MRI features with those of patients that did not present the same evolution. Methods: Multimodal MRI of 43 children treated for DIPG were retrospectively selected at four time points: baseline, after-radiotherapy, during true-progression, and at the last-visit...
December 13, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29241176/surgery-of-intracranial-gliomas-in-children
#10
James A Balogun, James T Rutka
Gliomas are the most common type of brain cancer in the pediatric patients, constituting about 50% of all childhood intracranial tumors. This is a highly heterogeneous group, varying from the benign WHO histopathological grades I and II to malignant WHO grades III and IV. The histology and location are significant prognostic factors, which influence the decision for surgical intervention, as well as the extent of possible tumor removal. In low-grade gliomas, surgery remains the initial option and should be directed at gross total resection in favorable locations, such as the cerebral hemispheres and the cerebellum...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29207163/preclinical-analysis-of-mtor-complex-1-2-inhibition-in-diffuse-intrinsic-pontine-glioma
#11
Patrick C Flannery, John A DeSisto, Vladimir Amani, Sujatha Venkataraman, Rakeb T Lemma, Eric W Prince, Andrew Donson, Erin E Moroze, Lindsey Hoffman, Jean M Mulcahy Levy, Nicholas Foreman, Rajeev Vibhakar, Adam L Green
Diffuse intrinsic pontine glioma (DIPG) is an incurable childhood brain tumor. The mechanistic target of rapamycin (MTOR), a key oncogene, functions as two distinct signaling complexes, MTORC1 and MTORC2. We set out to determine the preclinical efficacy and mechanism of action of MTOR inhibitors in DIPG. We evaluated the MTORC1 inhibitor everolimus and the MTORC1/2 inhibitor AZD2014 in three patient-derived DIPG cell lines using cell culture models. We created dose-response curves for both compounds. We measured phenotypic effects on cell self-renewal, apoptosis, cell cycle, differentiation, senescence, and autophagy...
November 29, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29203539/novel-and-shared-neoantigen-derived-from-histone-3-variant-h3-3k27m-mutation-for-glioma-t-cell-therapy
#12
Zinal S Chheda, Gary Kohanbash, Kaori Okada, Naznin Jahan, John Sidney, Matteo Pecoraro, Xinbo Yang, Diego A Carrera, Kira M Downey, Shruti Shrivastav, Shuming Liu, Yi Lin, Chetana Lagisetti, Pavlina Chuntova, Payal B Watchmaker, Sabine Mueller, Ian F Pollack, Raja Rajalingam, Angel M Carcaboso, Matthias Mann, Alessandro Sette, K Christopher Garcia, Yafei Hou, Hideho Okada
The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector...
December 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29198324/developing-chemotherapy-for-diffuse-pontine-intrinsic-gliomas-dipg
#13
REVIEW
Ho-Shin Gwak, Hyeon Jin Park
Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation. Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29198053/diffuse-intrinsic-pontine-gliomas-dipg-at-recurrence-is-there-a-window-to-test-new-therapies-in-some-patients
#14
M J Lobon-Iglesias, G Giraud, D Castel, C Philippe, M A Debily, C Briandet, F Fouyssac, E de Carli, C Dufour, D Valteau-Couanet, C Sainte-Rose, T Blauwblomme, K Beccaria, M Zerah, S Puget, R Calmon, N Boddaert, S Bolle, P Varlet, J Grill
Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials...
December 2, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29189105/characterization-of-diffuse-intrinsic-pontine-glioma-radiosensitivity-using-synchrotron-microbeam-radiotherapy-and-conventional-radiation-therapy-in-vitro
#15
L M Smyth, P A W Rogers, J C Crosbie, J F Donoghue
Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy modality that has been proposed as an alternative to conventional radiation therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a devastating pediatric tumor of the brainstem. The primary goal of this study was to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761 and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that these DIPG cell lines would exhibit differential responses to each radiation modality...
November 30, 2017: Radiation Research
https://www.readbyqxmd.com/read/29165288/treatment-related-noncontiguous-radiologic-changes-in-children-with-diffuse-intrinsic-pontine-glioma-treated-with-expanded-irradiation-fields-and-antiangiogenic-therapy
#16
Zoltan Patay, Thomas E Merchant, Rosa Nguyen, Christopher R Pierson, Arzu Onar-Thomas, Alberto Broniscer
PURPOSE: We previously reported the cases of 3 children with diffuse intrinsic pontine glioma (DIPG) in whom noncontiguous treatment-related abnormalities (NCTRAs) developed in the brain after expanded-field radiation therapy (RT). To investigate the occurrence and putative mechanism of NCTRAs, we reviewed brain magnetic resonance imaging studies of patients with DIPG treated in 2 consecutive phase I clinical trials (trials 1 and 2). METHODS AND MATERIALS: The 55 children included in these trials received small-molecule inhibitors: vandetanib in trial 1 (n=32; mean age 6...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29164272/signaling-pathways-and-mesenchymal-transition-in-pediatric-high-grade-glioma
#17
REVIEW
Michaël H Meel, Sophie A Schaper, Gertjan J L Kaspers, Esther Hulleman
Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible...
November 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29164054/effective-drug-delivery-in-diffuse-intrinsic-pontine-glioma-a-theoretical-model-to-identify-potential-candidates
#18
Fatma E El-Khouly, Dannis G van Vuurden, Thom Stroink, Esther Hulleman, Gertjan J L Kaspers, N Harry Hendrikse, Sophie E M Veldhuijzen van Zanten
Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED) may increase their therapeutic potential...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29151166/t2-weighted-images-are-superior-to-other-mr-image-types-for-the-determination-of-diffuse-intrinsic-pontine-glioma-intratumoral-heterogeneity
#19
Stephen Harward, S Harrison Farber, Michael Malinzak, Oren Becher, Eric M Thompson
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) remains the main cause of death in children with brain tumors. Given the inefficacy of numerous peripherally delivered agents to treat DIPG, convection enhanced delivery (CED) of therapeutic agents is a promising treatment modality. The purpose of this study was to determine which MR imaging type provides the best discrimination of intratumoral heterogeneity to guide future stereotactic implantation of CED catheters into the most cellular tumor regions...
November 18, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#20
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
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