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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/28099914/advances-in-epigenetic-glioblastoma-therapy
#1
Dong Hoon Lee, Hyun-Wook Ryu, Hye-Rim Won, So Hee Kwon
Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults despite contemporary gold-standard first-line treatment strategies. This type of tumor recurs in virtually all patients and no commonly accepted standard treatment exists for the recurrent disease. Therefore, advances in all scientific and clinical aspects of GBM are urgently needed. Epigenetic mechanisms are one of the major factors contributing to the pathogenesis of cancers, including glioblastoma. Epigenetic modulators that regulate gene expression by altering the epigenome and non-histone proteins are being exploited as therapeutic drug targets...
January 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#2
Chiara Cilibrasi, Gabriele Riva, Gabriele Romano, Massimiliano Cadamuro, Riccardo Bazzoni, Valentina Butta, Laura Paoletta, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Roberto Giovannoni, Angela Bentivegna
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits...
2017: PloS One
https://www.readbyqxmd.com/read/28048805/su-f-r-42-association-of-radiomic-and-metabolic-tumor-volumes-in-radiation-treatment-of-glioblastoma-multiforme
#3
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/28046578/su-f-t-392-superior-brainstem-and-cochlea-sparing-with-vmat-for-glioblastoma-multiforme
#4
T M Briere, M F McAleer, L B Levy, J N Yang, M D Anderson
PURPOSE: Volumetric arc therapy (VMAT) can provide similar target coverage and normal tissue sparing as IMRT but with shorter treatment times. At our institution VMAT was adopted for the treatment glioblastoma multiforme (GBM) after a small number of test plans demonstrated its non-inferiority. In this study, we compare actual clinical treatment plans for a larger cohort of patients treated with either VMAT or IMRT. METHODS: 90 GBM patients were included in this study, 45 treated with IMRT and 45 with VMAT...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28011764/inhibition-of-radiation-induced-glioblastoma-invasion-by-genetic-and-pharmacological-targeting-of-mda-9-syntenin
#5
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
#6
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/28011044/association-of-radiomics-and-metabolic-tumor-volumes-in-radiation-treatment-of-glioblastoma-multiforme
#7
Christopher J Lopez, Natalya Nagornaya, Nestor A Parra, Deukwoo Kwon, Fazilat Ishkanian, Arnold M Markoe, Andrew Maudsley, Radka Stoyanova
PURPOSE: To build a framework for investigation of the associations between imaging, clinical target volumes (CTVs), and metabolic tumor volumes (MTVs) features for better understanding of the underlying information in the CTVs and dependencies between these volumes. High-throughput extraction of imaging and metabolomic quantitative features from magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging of glioblastoma multiforme (GBM) results in tens of variables per patient...
November 15, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28003805/glioblastoma-stem-like-cells-characteristics-microenvironment-and-therapy
#8
REVIEW
Yang Yi, I-Yun Hsieh, Xiaojia Huang, Jie Li, Wei Zhao
Glioblastoma multiforme (GBM), grade IV astrocytoma, is the most fatal malignant primary brain tumor. GBM contains functional subsets of cells called glioblastoma stem-like cells (GSCs), which are radioresistant and chemoresistant and eventually lead to tumor recurrence. Recent studies showed that GSCs reside in particular tumor niches that are necessary to support their behavior. To successfully eradicate GBM growth and recurrence, new strategies selectively targeting GSCs and/or their microenvironmental niche should be designed...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27993114/hitting-a-moving-target-glioma-stem-cells-demand-new-approaches-in-glioblastoma-therapy
#9
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
https://www.readbyqxmd.com/read/27911279/microrna-101-inhibits-proliferation-migration-and-invasion-of-human-glioblastoma-by-targeting-sox9
#10
Nan Liu, Lei Zhang, Zhen Wang, Yingduan Cheng, Pengxing Zhang, Xin Wang, Weihong Wen, Hongwei Yang, Hui Liu, Weilin Jin, Yongsheng Zhang, Yanyang Tu
Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903197/upfront-boost-gamma-knife-leading-edge-radiosurgery-to-flair-mri-defined-tumor-migration-pathways-in-174-patients-with-glioblastoma-multiforme-a-15-year-assessment-of-a-novel-therapy
#11
Christopher M Duma, Brian S Kim, Peter V Chen, Marianne E Plunkett, Ralph Mackintosh, Marlon S Mathews, Ryan M Casserly, Gustavo A Mendez, Daniel J Furman, Garrett Smith, Nathan Oh, Chad A Caraway, Ami R Sanathara, Robert O Dillman, Azzurra-Sky Riley, David Weiland, Lian Stemler, Ruslana Cannell, Daniela Alexandru Abrams, Alexa Smith, Christopher M Owen, Burton Eisenberg, Michael Brant-Zawadzki
OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27836464/apoptotic-effect-of-atorvastatin-in-glioblastoma-spheroids-tumor-cultured-in-fibrin-gel
#12
Neda Bayat, Somayeh Ebrahimi-Barough, Abbas Norouzi-Javidan, Hooshang Saberi, Roksana Tajerian, Mohammad Mehdi Mokhtari Ardakan, Sadegh Shirian, Arman Ai, Jafar Ai
OBJECTIVE: Glioblastoma multiform (GBM) is one of the most common and highly aggressive primary brain tumors that thought to be of glial cells origin. The new available therapy for glioblastoma is based on better understanding of molecular malignant progression in this tumor. It is better to identify key molecular targets stimulating signaling pathways that lead to initiation of apoptosis for treatment of glioblastoma. Tumorigenesis broadly is controlled by tumor microenvironment and design of best biomimetic culture systems dependency on these conditions allow for in vitro and in vivo tumor modeling for studies of cancer cells behavior to drugs...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27832326/silencing-of-histone-deacetylase-2-suppresses-malignancy-for-proliferation-migration-and-invasion-of-glioblastoma-cells-and-enhances-temozolomide-sensitivity
#13
Zhiqiang Zhang, Yunmin Wang, Jiehan Chen, Qijia Tan, Caijun Xie, Cong Li, Wengang Zhan, Mei Wang
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27815359/antibody-targeting-grp78-enhances-the-efficacy-of-radiation-therapy-in-human-glioblastoma-and-non-small-cell-lung-cancer-cell-lines-and-tumor-models
#14
David Ya Dadey, Vaishali Kapoor, Kelly Hoye, Arpine Khudanyan, Andrea Collins, Dinesh Thotala, Dennis E Hallahan
PURPOSE: Non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM) have poor median survival. NSCLC and GBM overexpress glucose regulated protein 78 (GRP78), which has a role in radioresistance and recurrence. In this study, we determined the effect of anti-GRP78 antibody and the combined effect of the anti-GRP78 antibody with ionizing radiation (XRT) on NSCLC and GBM cell lines both in vitro and in vivo. EXPERIMENTAL DESIGN: NSCLC and GBM cancer cell lines were treated with anti-GRP78 antibodies and evaluated for proliferation, colony formation, cell death and PI3K/Akt/mTOR signaling...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27794494/a-non-viral-suicide-gene-delivery-system-traversing-the-blood-brain-barrier-for-non-invasive-glioma-targeting-treatment
#15
Shiqian Gao, Huayu Tian, Zhenkai Xing, Dawei Zhang, Ye Guo, Zhaopei Guo, Xiaojuan Zhu, Xuesi Chen
Herpes simplex virus type I thymidine kinase gene (HSV-TK) in viral vector is a promising strategy against glioblastoma multiforme (GBM). However, the biosafety risk restricts its application in clinic. In this work, poly (l-lysine)-grafted polyethylenimine (PEI-PLL), which combines the high transfection efficiency of polyethylenimine and the good biodegradability of poly (l-lysine), was adopted as the non-viral vector backbone. Angiopep-2, a blood brain barrier (BBB) crossing and glioma targeting bifunctional peptide was conjugated on PEI-PLL via polyethyleneglycol (PEG) and designated as PPA...
December 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27783662/mertk-inhibition-induces-polyploidy-and-promotes-cell-death-and-cellular-senescence-in-glioblastoma-multiforme
#16
Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
https://www.readbyqxmd.com/read/27779678/heb-silencing-induces-anti-proliferative-effects-on-u87mg-cells-cultured-as-neurospheres-and-monolayers
#17
Paulo R D V Godoy, Ana Paula L Montaldi, Elza T Sakamoto-Hojo
Glioblastoma multiforme (GBM) is a lethal tumor and novel strategies are required to overcome resistance. Transcription factor 12 (HEB) has been associated with neural and stem cell proliferation, is overexpressed in certain tumor types and is induced in irradiated U87MG cells. The present study aimed to determine whether HEB knockdown, with or without irradiation, may sensitize GBM cells. U87MG GBM and ACBRI‑371 primary human astrocytes were cultured in monolayers or neurospheres. Cell proliferation and death, cell cycle and sub‑G1 detection, and cluster of differentiation (CD) 133 immunofluorescence were analyzed by flow cytometry, whereas HEB protein expression was analyzed by immunocytochemistry and western blotting...
December 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27764801/foxm1-and-stat3-interaction-confers-radioresistance-in-glioblastoma-cells
#18
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27732951/ikk-nf-%C3%AE%C2%BAb-signaling-contributes-to-glioblastoma-stem-cell-maintenance
#19
Amanda L Rinkenbaugh, Patricia C Cogswell, Barbara Calamini, Denise E Dunn, Anders I Persson, William A Weiss, Donald C Lo, Albert S Baldwin
Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. Glioblastoma stem cells (GSCs) drive tumor formation, invasion, and drug resistance and, as such, are the focus of studies to identify new therapies for disease control. Here, we identify the involvement of IKK and NF-κB signaling in the maintenance of GSCs. Inhibition of this pathway impairs self-renewal as analyzed in tumorsphere formation and GBM expansion as analyzed in brain slice culture. Interestingly, both the canonical and non-canonical branches of the NF-κB pathway are shown to contribute to this phenotype...
October 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27713511/cell-surface-grp78-as-a-biomarker-and-target-for-suppressing-glioma-cells
#20
Bo Ram Kang, Seung-Hoon Yang, Bo-Ryehn Chung, Woong Kim, YoungSoo Kim
High-grade glioma is a highly malignant and metastatic brain cancer, resistant to many existing anticancer treatments. In such glioma cancer cells, the glucose-regulated protein 78 kDa (GRP78) is particularly highly up-regulated. Former studies have thus targeted mutation-free GRP78 not only to detect glioma cancer cells specifically but also to enhance cytotoxic effect. We focus on cell surface-expressed GRP78 as a target for suppressing high-grade glioma cell lines. Glioblastoma multiforme (GBM) cell line, highly malignant glioma cells, was first injected into 5-week-old athymic mice to confirm and compare GRP78 expression in vivo in xenografted and normal brain tissue...
October 7, 2016: Scientific Reports
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