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https://www.readbyqxmd.com/read/29244086/cerebral-blood-flow-changes-after-radiation-therapy-identifies-pseudo-progression-in-diffuse-intrinsic-pontine-gliomas
#1
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/29207163/preclinical-analysis-of-mtor-complex-1-2-inhibition-in-diffuse-intrinsic-pontine-glioma
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/29143272/preliminary-results-of-immune-modulating-antibody-mdv9300-pidilizumab-treatment-in-children-with-diffuse-intrinsic-pontine-glioma
#12
Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Helen Toledano, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Michael Weintraub, Mony Benifla
Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study...
November 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29118968/combination-of-ezh2-inhibitor-and-bet-inhibitor-for-treatment-of-diffuse-intrinsic-pontine-glioma
#13
Yaqin Zhang, Weijie Dong, Junying Zhu, Lizhu Wang, Xinjian Wu, Hong Shan
Background: Diffuse intrinsic pontine glioma is an infiltrative, often high-grade glioma of the brainstem that is not amenable to surgical resection. The current treatment of DIPG by radiation therapy showed dramatically improvement of patient's condition, however, the tumor recurs rapidly. More and more studies are focused on the genetic and epigenetic drivers of DIPGs, which may provide more and more novel therapy target for DIPG. EZH2 has been proved to be a potential therapeutic target for H3K27M-mutant pediatric gliomas recently...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29100338/patient-derived-dipg-cells-preserve-stem-like-characteristics-and-generate-orthotopic-tumors
#14
Cheng Xu, Xiaoqing Liu, Yibo Geng, Qingran Bai, Changcun Pan, Yu Sun, Xin Chen, Hai Yu, Yuliang Wu, Peng Zhang, Wenhao Wu, Yu Wang, Zhen Wu, Junting Zhang, Zhaohui Wang, Rui Yang, Jenna Lewis, Darell Bigner, Fangping Zhao, Yiping He, Hai Yan, Qin Shen, Liwei Zhang
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor, with a median survival of less than one year. Due to enormous difficulties in the acquisition of DIPG specimens and the sophisticated technique required to perform brainstem orthotopic injection, only a handful of DIPG pre-clinical models are available. In this study, we successfully established eight patient-derived DIPG cell lines, mostly derived from treatment-naïve surgery or biopsy specimens. These patient-derived cell lines can be stably passaged in serum-free neural stem cell media and displayed distinct morphologies, growth rates and chromosome abnormalities...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29090526/a-pediatric-brain-tumor-consortium-phase-ii-trial-of-capecitabine-rapidly-disintegrating-tablets-with-concomitant-radiation-therapy-in-children-with-newly-diagnosed-diffuse-intrinsic-pontine-gliomas
#15
Lindsay B Kilburn, Mehmet Kocak, Patricia Baxter, Tina Young Poussaint, Arnold C Paulino, Christine McIntyre, Annabelle Lemenuel-Diot, Christine Lopez-Diaz, Larry Kun, Murali Chintagumpala, Jack M Su, Alberto Broniscer, Justin N Baker, Eugene I Hwang, Maryam Fouladi, James M Boyett, Susan M Blaney
BACKGROUND: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). PATIENTS AND METHODS: Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m(2) /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT...
November 1, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29057192/palliative-care-options-for-a-young-adult-patient-with-a-diffuse-intrinsic-pontine-glioma
#16
Julian Sison, Hung Tran, Ashley Margol, Nishant Tiwari, Karla M Garcia, Jennifer Cotter, Erin Kiehna, Arthur J Olch, Kenneth Wong
Diffuse intrinsic pontine gliomas (DIPGs) are rare but devastating brain tumors that occur primarily in children. These gliomas have poor prognoses and present options focus on palliation of symptoms and prolongation of life. Here, we present a case of a 16-year-old female diagnosed with a DIPG whose age group has been mostly left out of discussions regarding psychosocial support options. This report is meant to start a conversation about the different support options available at our institution that have shown promising results in the literature for palliative care applications...
August 18, 2017: Curēus
https://www.readbyqxmd.com/read/29022050/concurrent-radiotherapy-with-temozolomide-vs-concurrent-radiotherapy-with-a%C3%A2-cisplatinum-based-polychemotherapy-regimen-acute-toxicity-in-pediatric-high-grade-glioma-patients
#17
Clemens Seidel, André O von Bueren, Sabrina Bojko, Marion Hoffmann, Torsten Pietsch, Gerrit H Gielen, Monika Warmuth-Metz, Brigitte Bison, Rolf-D Kortmann, Christof M Kramm
PURPOSE: As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments. METHODS: Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials...
October 11, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28968963/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#18
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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28959975/targeting-neuronal-activity-regulated-neuroligin-3-dependency-in-high-grade-glioma
#19
Humsa S Venkatesh, Lydia T Tam, Pamelyn J Woo, James Lennon, Surya Nagaraja, Shawn M Gillespie, Jing Ni, Damien Y Duveau, Patrick J Morris, Jean J Zhao, Craig J Thomas, Michelle Monje
High-grade gliomas (HGG) are a devastating group of cancers, and represent the leading cause of brain tumour-related death in both children and adults. Therapies aimed at mechanisms intrinsic to glioma cells have translated to only limited success; effective therapeutic strategies will need also to target elements of the tumour microenvironment that promote glioma progression. Neuronal activity promotes the growth of a range of molecularly and clinically distinct HGG types, including adult and paediatric glioblastoma (GBM), anaplastic oligodendroglioma, and diffuse intrinsic pontine glioma (DIPG)...
September 28, 2017: Nature
https://www.readbyqxmd.com/read/28947983/deceptive-morphologic-and-epigenetic-heterogeneity-in-diffuse-intrinsic-pontine-glioma
#20
Marianna Bugiani, Sophie E M Veldhuijzen van Zanten, Viola Caretti, Pepijn Schellen, Eleonora Aronica, David P Noske, William P Vandertop, Gertjan J L Kaspers, Dannis G van Vuurden, Pieter Wesseling, Esther Hulleman
Historically, the diagnosis of diffuse intrinsic pontine glioma (DIPG) was based on typical imaging findings and clinical characteristics instead of pathology. However, the discovery of mutations in histone H3 variants, and the availability of tumor material for molecular analysis, has led to a paradigm shift in DIPG research and clinical practice. Using data from whole-brain autopsies in a series of nine DIPG patients with known histone mutational status, we here aim to review histopathological characteristics with special focus on intratumoral heterogeneity (ITH) and histone 3 K27 trimethylation (H3 K27me3)...
September 1, 2017: Oncotarget
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