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https://www.readbyqxmd.com/read/28103265/rabbit-model-of-human-gliomas-implications-for-intra-arterial-drug-delivery
#1
Huamin Qin, Miroslaw Janowski, Monica S Pearl, Izabela Malysz-Cymborska, Shen Li, Charles G Eberhart, Piotr Walczak
The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices...
2017: PloS One
https://www.readbyqxmd.com/read/28101701/early-postoperative-tumor-progression-predicts-clinical-outcome-in-glioblastoma-implication-for-clinical-trials
#2
Andreas Merkel, Dorothea Soeldner, Christina Wendl, Dilek Urkan, Joji B Kuramatsu, Corinna Seliger, Martin Proescholdt, Ilker Y Eyupoglu, Peter Hau, Martin Uhl
Molecular markers define the diagnosis of glioblastoma in the new WHO classification of 2016, challenging neuro-oncology centers to provide timely treatment initiation. The aim of this study was to determine whether a time delay to treatment initiation was accompanied by signs of early tumor progression in an MRI before the start of radiotherapy, and, if so, whether this influences the survival of glioblastoma patients. Images from 61 patients with early post-surgery MRI and a second MRI just before the start of radiotherapy were examined retrospectively for signs of early tumor progression...
January 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#3
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28091986/shift-of-microrna-profile-upon-glioma-cell-migration-using-patient-derived-spheroids-and-serum-free-conditions
#4
Sune Munthe, Bo Halle, Henning B Boldt, Helle Christiansen, Steffen Schmidt, Vivek Kaimal, Jessica Xu, Sonya Zabludoff, Jan Mollenhauer, Frantz R Poulsen, Bjarne W Kristensen
Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions...
January 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28076755/rad51-is-a-selective-dna-repair-target-to-radiosensitize-glioma-stem-cells
#5
Harry O King, Tim Brend, Helen L Payne, Alexander Wright, Thomas A Ward, Karan Patel, Teklu Egnuni, Lucy F Stead, Anjana Patel, Heiko Wurdak, Susan C Short
Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28070830/mesenchymal-subtype-of-glioblastomas-with-high-dna-pkcs-expression-is-associated-with-better-response-to-radiotherapy-and-temozolomide
#6
Baptiste Pinel, Mathilde Duchesne, Julie Godet, Serge Milin, Antoine Berger, Michel Wager, Lucie Karayan-Tapon
A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of mesenchymal (MES) and proneural (PN) subtypes. Tumors from 122 patients with a glioblastoma treated at the University Hospital of Poitiers between 2002-2013 by an association of radiotherapy and temozolomide were collected...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28049492/current-status-and-perspectives-of-interventional-clinical-trials-for-glioblastoma-analysis-of-clinicaltrials-gov
#7
REVIEW
Nikola Cihoric, Alexandros Tsikkinis, Giuseppe Minniti, Frank J Lagerwaard, Ulrich Herrlinger, Etienne Mathier, Ivan Soldatovic, Branislav Jeremic, Pirus Ghadjar, Olgun Elicin, Kristina Lössl, Daniel M Aebersold, Claus Belka, Evelyn Herrmann, Maximilian Niyazi
The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements...
January 3, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28049229/tandem-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-high-grade-gliomas-in-children-and-adolescents
#8
Ji Won Lee, Do Hoon Lim, Ki Woong Sung, Hyeong Jin Lee, Eun Sang Yi, Keon Hee Yoo, Hong Hoe Koo, Yeon Lim Suh, Hyung Jin Shin
With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28048805/su-f-r-42-association-of-radiomic-and-metabolic-tumor-volumes-in-radiation-treatment-of-glioblastoma-multiforme
#9
C Lopez, N Nagornaya, N Parra, D Kwon, F Ishkanian, A Markoe, A Maudsley, R Stoyanova
PURPOSE: High-throughput extraction of imaging and metabolomic quantitative features from MRI and MR Spectroscopy Imaging (MRSI) of Glioblastoma Multiforme (GBM) results in tens of variables per patient. In radiotherapy (RT) of GBM, the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl Aspartate (NAA) and Choline (Cho). Corresponding Clinical Target Volumes (CTVs) for RT planning are based on Contrast Enhancing T1-weighted MRI (CE-T1w) and T2-weighted/Fluid Attenuated Inversion Recovery (FLAIR) MRI...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047107/su-f-t-497-spatiotemporally-optimal-personalized-prescription-scheme-for-glioblastoma-patients-using-the-proliferation-and-invasion-glioma-model
#10
M Kim, J Rockhill, M Phillips
PURPOSE: To investigate a spatiotemporally optimal radiotherapy prescription scheme and its potential benefit for glioblastoma (GBM) patients using the proliferation and invasion (PI) glioma model. METHODS: Standard prescription for GBM was assumed to deliver 46Gy in 23 fractions to GTV1+2cm margin and additional 14Gy in 7 fractions to GTV2+2cm margin. We simulated the tumor proliferation and invasion in 2D according to the PI glioma model with a moving velocity of 0...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046283/su-f-r-04-radiomics-for-survival-prediction-in-glioblastoma-gbm
#11
H Zhang, J Molitoris, S Tan, I Giacomelli, D Scartoni, C Gzell, N Bhooshan, W Choi, W Lu, M Mehta, W D'Souza
PURPOSE: To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT). METHODS: 28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28035389/role-of-mir-223-paired-box-6-signaling-in-temozolomide-chemoresistance-in-glioblastoma-multiforme-cells
#12
Quan Cheng, Xiaoqiang Ma, Hui Cao, Zigui Chen, Xin Wan, Rui Chen, Renjun Peng, Jun Huang, Bing Jiang
Glioblastoma (GBM) is the predominant and most fatal type of brain tumor in adults. The prognosis of GBM remains poor despite advances in surgery, chemotherapy and radiotherapy. It is common that patients with GBM exhibit innate or acquired resistance to temozolomide (TMZ), a standard chemotherapeutic agent for GBM, and a previous report demonstrated that miRNA‑233 (miR‑223) promotes the growth and invasion of GBM cells by targeting tumor suppressor paired box 6 (PAX6). The present study explored the effect of TMZ on miR‑223/PAX6 signaling in addition to the effect of miR‑223/PAX6 signaling on TMZ chemoresistance in human GBM cells...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28025828/prognostic-parameters-and-outcome-after-re-irradiation-for-progressive-glioblastoma
#13
K Zwirner, F Paulsen, J Schittenhelm, C Borchers, M Skardelly, D Zips, F Eckert
OBJECTIVES: In progressive glioblastoma, salvage treatment remains unstandardized, response is highly variable, and detailed analysis of individual approaches is mandatory. Re-irradiation is an established option in the therapy of progressive glioblastoma. Thus, we analysed outcome and prognostic parameters of patients with re-irradiated glioblastoma treated at our institution since 1998. MATERIALS AND METHODS: In a total of 51 patients, clinical and treatment parameters were collected and analysed retrospectively...
December 26, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28011886/regression-of-a-glioblastoma-multiforme-spontaneous-versus-a-potential-antineoplastic-effect-of-dexamethasone-and-levetiracetam
#14
Prakash Peddi, Nisha Elizabeth Ajit, Gary Von Burton, Hazem El-Osta
Patients with grade IV astrocytoma or glioblastoma multiforme (GBM) have a median survival of <12 months, increased to 14.6 months by maximal safe resection with radiation and temozolamide. In the absence of chemotherapy, radiotherapy or chemoradiotherapy, spontaneous regression of GBM or regression while only being on dexamethasone (DEX) and levetiracetam (LEV) have seldom been reported. Here, we present a case of a patient who had significant regression of the GBM with DEX and LEV alone. In this study, we hypothesise a plausible antineoplastic role of DEX and or LEV in GBM and highlight molecular, preclinical and clinical studies supporting this role...
December 23, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/28011764/inhibition-of-radiation-induced-glioblastoma-invasion-by-genetic-and-pharmacological-targeting-of-mda-9-syntenin
#15
Timothy P Kegelman, Bainan Wu, Swadesh K Das, Sarmistha Talukdar, Jason M Beckta, Bin Hu, Luni Emdad, Kristoffer Valerie, Devanand Sarkar, Frank B Furnari, Webster K Cavenee, Jun Wei, Angela Purves, Surya K De, Maurizio Pellecchia, Paul B Fisher
Glioblastoma multiforme (GBM) is an intractable tumor despite therapeutic advances, principally because of its invasive properties. Radiation is a staple in therapeutic regimens, although cells surviving radiation can become more aggressive and invasive. Subtraction hybridization identified melanoma differentiation-associated gene 9 [MDA-9/Syntenin; syndecan-binding protein (SDCBP)] as a differentially regulated gene associated with aggressive cancer phenotypes in melanoma. MDA-9/Syntenin, a highly conserved double-PDZ domain-containing scaffolding protein, is robustly expressed in human-derived GBM cell lines and patient samples, with expression increasing with tumor grade and correlating with shorter survival times and poorer response to radiotherapy...
December 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#16
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28007652/characteristics-of-sulfasalazine-induced-cytotoxicity-in-c6-rat-glioma-cells
#17
Raffaela Silvestre Ignarro, Gustavo Facchini, Daniela Rodrigues de Melo, Karin Juliane Pelizzaro-Rocha, Carmen Veríssima Ferreira, Roger Frigério Castilho, Fabio Rogerio
Glioblastoma is the most aggressive primary brain tumor. Surgical resection, radiotherapy and temozolomide (TMZ), an alkylating agent, is the standard of care. Glioma cells may synthetize the antioxidant glutathione by importing cystine through a cystine/glutamate antiporter, which is inhibited by sulfasalazine (SAS). C6 rat glioma cells are largely used in in vitro and in vivo models for developing new glioblastoma treatment strategies. We treated C6 cells with 25μM TMZ and/or 0.25mM or 0.5mM SAS for 1, 3 or 5days and evaluated viability, apoptosis, total glutathione levels and metalloproteinase MMP2 and MMP9 activities...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28001091/treatment-options-for-recurrent-high-grade-gliomas
#18
Harjus S Birk, Seunggu J Han, Nicholas A Butowski
High-grade gliomas are aggressive brain tumors encompassing Grade III and IV classifications. Of these, glioblastoma (GB) is the most malignant with a high rate of recurrence after initial resection. Although standard treatment does exist for newly diagnosed GBs, therapeutic strategies for recurrent GB are less solidified. However, mounting evidence describes the role of re-resection, bevacizumab, chemotherapy, targeted molecular therapies, immunotherapeutic approaches and radiotherapy in recurrent GB management...
January 2017: CNS Oncology
https://www.readbyqxmd.com/read/27993569/a-genome-based-model-for-adjusting-radiotherapy-dose-gard-a-retrospective-cohort-based-study
#19
Jacob G Scott, Anders Berglund, Michael J Schell, Ivaylo Mihaylov, William J Fulp, Binglin Yue, Eric Welsh, Jimmy J Caudell, Kamran Ahmed, Tobin S Strom, Eric Mellon, Puja Venkat, Peter Johnstone, John Foekens, Jae Lee, Eduardo Moros, William S Dalton, Steven A Eschrich, Howard McLeod, Louis B Harrison, Javier F Torres-Roca
BACKGROUND: Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose. METHODS: We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD)...
December 18, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27993114/hitting-a-moving-target-glioma-stem-cells-demand-new-approaches-in-glioblastoma-therapy
#20
Drew A Spencer, Brenda M Auffinger, Jason P Murphy, Megan E Muroski, Jian Qiao, Yureve Govind, Maciej S Lesniak
Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype...
December 15, 2016: Current Cancer Drug Targets
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