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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/28408882/targeted-nanotechnology-in-glioblastoma-multiforme
#1
REVIEW
Talita Glaser, Inbo Han, Liquan Wu, Xiang Zeng
Gliomas, and in particular glioblastoma multiforme, are aggressive brain tumors characterized by a poor prognosis and high rates of recurrence. Current treatment strategies are based on open surgery, chemotherapy (temozolomide) and radiotherapy. However, none of these treatments, alone or in combination, are considered effective in managing this devastating disease, resulting in a median survival time of less than 15 months. The efficiency of chemotherapy is mainly compromised by the blood-brain barrier (BBB) that selectively inhibits drugs from infiltrating into the tumor mass...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28392144/iridium-knife-another-knife-in-radiation-oncology
#2
Natasa Milickovic, Nikolaos Tselis, Efstratios Karagiannis, Konstantinos Ferentinos, Nikolaos Zamboglou
PURPOSE: Intratarget dose escalation with superior conformity is a defining feature of three-dimensional (3D) iridium-192 ((192)Ir) high-dose-rate (HDR) brachytherapy (BRT). In this study, we analyzed the dosimetric characteristics of interstitial (192)Ir HDR BRT for intrathoracic and cerebral malignancies. We examined the dose gradient sharpness of HDR BRT compared with that of linear accelerator-based stereotactic radiosurgery and stereotactic body radiation therapy, usually called X-Knife, to demonstrate that it may as well be called a Knife...
April 6, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28350082/hotair-upregulates-an-18-gene-cell-cycle-related-mrna-network-in-glioma
#3
Kai Huang, Jia Sun, Chao Yang, Yunfei Wang, Bingcong Zhou, Chunsheng Kang, Lei Han, Qixue Wang
HOTAIR is a tumor promoting long non-coding RNA (lncRNA) with roles in multiple cancers. However, the role of HOTAIR in glioma has not been well charaterized. Genes that positively correlated with HOTAIR were identified from the Chinese Glioma Genome Atlas and constructed into an interacting network. In total, 18 genes with P-values <0.01 were further extracted and constructed into a subnetwork. Real-time PCR, western blot and immunofluorescence analyses were employed to examine the expression of the genes after HOTAIR overexpression or knockdown...
March 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28324583/revisiting-cdk-inhibitors-for-treatment-of-glioblastoma-multiforme
#4
REVIEW
Dorota Lubanska, Lisa Porter
Despite extensive efforts and continual progress in research and medicine, outcomes for patients with high-grade glioma remain exceptionally poor. Over the past decade, research has revealed a great deal about the complex biology behind glioma development, and has brought to light some of the major barriers preventing successful treatment. Glioblastoma multiforme (GBM) (stage 4 astrocytoma) is a highly dynamic tumour and one of the most extreme examples of intratumoural heterogeneity, making targeting with specific therapeutics an inefficient and highly unpredictable goal...
March 21, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28323865/the-microrna-302b-inhibited-insulin-like-growth-factor-binding-protein-2-signaling-pathway-induces-glioma-cell-apoptosis-by-targeting-nuclear-factor-ia
#5
Chin-Cheng Lee, Peng-Hsu Chen, Kuo-Hao Ho, Chwen-Ming Shih, Chia-Hsiung Cheng, Cheng-Wei Lin, Kur-Ta Cheng, Ann-Jeng Liu, Ku-Chung Chen
MicroRNAs are small noncoding RNAs that post-transcriptionally control the expression of genes involved in glioblastoma multiforme (GBM) development. Although miR-302b functions as a tumor suppressor, its role in GBM is still unclear. Therefore, this study comprehensively explored the roles of miR-302b-mediated gene networks in GBM cell death. We found that miR-302b levels were significantly higher in primary astrocytes than in GBM cell lines. miR-302b overexpression dose dependently reduced U87-MG cell viability and induced apoptosis through caspase-3 activation and poly(ADP ribose) polymerase degradation...
2017: PloS One
https://www.readbyqxmd.com/read/28314870/perillyl-alcohol-a-pleiotropic-natural-compound-suitable-for-brain-tumor-therapy-targets-free-radicals
#6
REVIEW
Aline C Gomes, Angélica L Mello, Manuel G Ribeiro, Diogo G Garcia, Clovis O Da Fonseca, Marcela D'Alincourt Salazar, Axel H Schönthal, Thereza Quirico-Santos
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis...
March 17, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28314270/global-microrna-expression-profiling-identifies-unique-microrna-pattern-of-radioresistant-glioblastoma-cells
#7
Jakub Ondracek, Pavel Fadrus, Jiri Sana, Andrej Besse, Tomas Loja, Marek Vecera, Lenka Radova, Martin Smrcka, Pavel Slampa, Ondrej Slaby
Glioblastoma multiforme (GBM) is the most aggressive intracranial tumor characterized with infaust prognosis. Despite advances in neurosurgical and radiotherapeutic techniques and chemotherapy, the median overall survival ranges between 12-15 months from diagnosis. The main cause of treatment failure is considered the presence of tumor cells resistant to conventional therapy, mainly radiotherapy. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and have been repeatedly proven to play important roles in pathogenesis and biological features of many cancers, including GBM and its radioresistant phenotype...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28299344/advances-in-immunotherapy-for-glioblastoma-multiforme
#8
REVIEW
Boyuan Huang, Hongbo Zhang, Lijuan Gu, Bainxin Ye, Zhihong Jian, Creed Stary, Xiaoxing Xiong
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28286871/semiautomated-workflow-for-clinically-streamlined-glioma-parametric-response-mapping
#9
Lauren Keith, Brian D Ross, Craig J Galbán, Gary D Luker, Stefanie Galbán, Binsheng Zhao, Xiaotao Guo, Thomas L Chenevert, Benjamin A Hoff
Management of glioblastoma multiforme remains a challenging problem despite recent advances in targeted therapies. Timely assessment of therapeutic agents is hindered by the lack of standard quantitative imaging protocols for determining targeted response. Clinical response assessment for brain tumors is determined by volumetric changes assessed at 10 weeks post-treatment initiation. Further, current clinical criteria fail to use advanced quantitative imaging approaches, such as diffusion and perfusion magnetic resonance imaging...
December 2016: Tomography: a Journal for Imaging Research
https://www.readbyqxmd.com/read/28283885/anti-inflammatory-effects-of-atorvastatin-by-suppressing-traf3ip2-and-il-17ra-in-human-glioblastoma-spheroids-cultured-in-a-three-dimensional-model-possible-relevance-to-glioblastoma-treatment
#10
Neda Bayat, Somayeh Ebrahimi-Barough, Abbas Norouzi-Javidan, Hooshang Saberi, Mohammad Mehdi Mokhtari Ardakan, Arman Ai, Mostafa Soleimannejad, Jafar Ai
Glioblastoma multiform (GBM) is a primary malignant brain tumor with a few therapeutic targets available for it. The interaction between the immune system and glioma is an important factor that could lead to novel therapeutic approaches to fight glioma. In this study, we investigated in vitro anti-inflammatory and apoptotic activity of atorvastatin in different concentrations 1, 5, and 10 μM on glioma spheroid cells cultured in a three-dimensional model in fibrin gel that indicate the complex in vivo microenvironment better than a simple two-dimensional cell culture...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28274139/immune-and-viral-therapies-for-malignant-primary-brain-tumors
#11
Andrew M Gardeck, Jordan Sheehan, Walter C Low
Glioblastoma multiforme (GBM) is a primary brain tumor with great lethality. Current standard of care with surgery, radiation therapy, and chemotherapy are ineffective in curing this disease. Recent advancements in biological therapies show promise in treating brain tumors. Areas covered: This article provides a review of: the peripheral activation of antigen presenting cells such as dendritic cells to stimulate T cells to recognize and destroy tumor cells within the brain; the ex vivo expansion and transfer of dendritic cells, T cells, and engineered T cells expressing chimeric antigen receptors to target cells bearing specific tumor antigens as well as monoclonal antibodies as immune check point inhibitors...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28157712/the-interference-of-notch1-target-hes1-affects-cell-growth-differentiation-and-invasiveness-of-glioblastoma-stem-cells-through-modulation-of-multiple-oncogenic-targets
#12
Carlo Cenciarelli, Hany E Marei, Manuela Zonfrillo, Patrizia Casalbore, Armando Felsani, Stefano Giannetti, Gianluca Trevisi, Asma Althani, Annunziato Mangiola
The invasive and lethal nature of Glioblastoma multiforme (GBM) necessitates the continuous identification of molecular targets and search of efficacious therapies to inhibit GBM growth. The GBM resistance to chemotherapy and radiation it is attributed to the existence of a rare fraction of cancer stem cells (CSC) that we have identified within the tumor core and in peritumor tissue of GBM. Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28153049/longitudinal-analysis-of-treatment-induced-genomic-alterations-in-gliomas
#13
E Zeynep Erson-Omay, Octavian Henegariu, S Bülent Omay, Akdes Serin Harmancı, Mark W Youngblood, Ketu Mishra-Gorur, Jie Li, Koray Özduman, Geneive Carrión-Grant, Victoria E Clark, Caner Çağlar, Mehmet Bakırcıoğlu, M Necmettin Pamir, Viviane Tabar, Alexander O Vortmeyer, Kaya Bilguvar, Katsuhito Yasuno, Lisa M DeAngelis, Joachim M Baehring, Jennifer Moliterno, Murat Günel
BACKGROUND: Glioblastoma multiforme (GBM) constitutes nearly half of all malignant brain tumors and has a median survival of 15 months. The standard treatment for these lesions includes maximal resection, radiotherapy, and chemotherapy; however, individual tumors display immense variability in their response to these approaches. Genomic techniques such as whole-exome sequencing (WES) provide an opportunity to understand the molecular basis of this variability. METHODS: Here, we report WES-guided treatment of a patient with a primary GBM and two subsequent recurrences, demonstrating the dynamic nature of treatment-induced molecular changes and their implications for clinical decision-making...
February 2, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28131906/a-novel-hdac6-inhibitor-tubastatin-a-controls-hdac6-p97-vcp-mediated-ubiquitination-autophagy-turnover-and-reverses-temozolomide-induced-er-stress-tolerance-in-gbm-cells
#14
Zong-Yang Li, Ce Zhang, Yuan Zhang, Lei Chen, Bao-Dong Chen, Qing-Zhong Li, Xie-Jun Zhang, Wei-Ping Li
Temozolomide (TMZ) is the cornerstone of therapy for glioblastoma multiforme (GBM). However, its efficacy is limited due to the development of multidrug resistance (MDR). In this study, we first identified the occurrence of ER stress-tolerance (ERST) in glioma cells and confirmed that ERST was positively correlated with TMZ resistance. We further showed that the seesaw-effect of HDAC6-p97/VCP (increased HDAC6 and decreased p97/VCP) in glioma cells was crucial to ERST-associated TMZ resistance. Moreover, the combination treatment of Tubastatin A (TUB, a selective inhibitor of HDAC6) and TMZ synergistically overcame ERST, reduced cell viability and induced apoptosis in TMZ-resistant glioma cells...
January 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28123308/strategies-of-temozolomide-in-future-glioblastoma-treatment
#15
REVIEW
Chooi Yeng Lee
Glioblastoma multiforme (GBM) may be one of the most challenging brain tumors to treat, as patients generally do not live more than 2 years. This review aimed to give a timely review of potential future treatments for GBM by looking at the latest strategies, involving mainly the use of temozolomide (TMZ). Although these studies were carried out either in vitro or in rodents, the findings collectively suggested that we are moving toward developing a more efficacious therapy for GBM patients. Nanoparticles preparation was, by far, the most extensively studied strategy for targeted brain delivery...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28099914/advances-in-epigenetic-glioblastoma-therapy
#16
REVIEW
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...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#17
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
#18
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
#19
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
#20
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...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
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