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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#1
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28484222/in-silico-evaluation-of-dna-damage-inducible-transcript-4-gene-ddit4-as-prognostic-biomarker-in-several-malignancies
#2
Joseph A Pinto, Christian Rolfo, Luis E Raez, Alexandra Prado, Jhajaira M Araujo, Leny Bravo, Williams Fajardo, Zaida D Morante, Alfredo Aguilar, Silvia P Neciosup, Luis A Mas, Denisse Bretel, Justin M Balko, Henry L Gomez
DDIT4 gene encodes a protein whose main action is to inhibit mTOR under stress conditions whilst several in vitro studies indicate that its expression favors cancer progression. We have previously described that DDIT4 expression is an independent prognostic factor for tripe negative breast cancer resistant to neoadjuvant chemotherapy. We herein report that high DDIT4 expression is related to the outcome (recurrence-free survival, time to progression and overall survival) in several cancer types. We performed in silico analysis in online platforms, in pooled datasets from KM Plotter and meta-analysis of individual datasets from SurvExpress...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483513/crgd-peptide-installed-epirubicin-loaded-polymeric-micelles-for-effective-targeted-therapy-against-brain-tumors
#3
S Quader, X Liu, Y Chen, P Mi, T Chida, T Ishii, Y Miura, N Nishiyama, H Cabral, K Kataoka
Current therapeutic strategies against glioblastoma multiforme (GBM) are futile mainly because of the poor access of drugs into malignant tissues, which is hindered by the tight blood-brain tumor barrier in the GBM vasculature. Nanomedicines have shown potential for circumventing the vascular barriers of GBM, particularly by targeting markers on the luminal side of endothelial cells in the blood vessels of GBM for achieving effective and selective translocation into the tumor. Thus, as the αvβ3 and αvβ5 integrins overexpressed on the endothelial cells of GBM can be targeted by cyclic-Arg-Gly-Asp (cRGD) peptide, herein, we developed cRGD-installed micellar nanomedicines loading epirubicin, the potent antiglioblastoma agent, through a pH-sensitive hydrazone-bond for effective treatment of GBM...
May 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28464840/sparing-of-normal-tissues-with-volumetric-arc-radiation-therapy-for-glioblastoma-single-institution-clinical-experience
#4
Tina Marie Briere, Mary Frances McAleer, Lawrence B Levy, James N Yang
BACKGROUND: Patients with glioblastoma multiforme (GBM) require radiotherapy as part of definitive management. Our institution has adopted the use of volumetric arc therapy (VMAT) due to superior sparing of the adjacent organs at risk (OARs) compared to intensity modulated radiation therapy (IMRT). Here we report our clinical experience by analyzing target coverage and sparing of OARs for 90 clinical treatment plans. METHODS: VMAT and IMRT patient cohorts comprising 45 patients each were included in this study...
May 2, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28459461/mir-181b-modulates-egfr-dependent-vcam-1-expression-and-monocyte-adhesion-in-glioblastoma
#5
Y-S Liu, H-Y Lin, S-W Lai, C-Y Huang, B-R Huang, P-Y Chen, K-C Wei, D-Y Lu
Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28443460/augmented-expression-of-runx1-deregulates-the-global-gene-expression-of-u87-glioblastoma-multiforme-cells-and-inhibits-tumor-growth-in-mice
#6
Yoel Bogoch, Gilgi Friedlander-Malik, Lior Lupu, Ekaterina Bondar, Nitzan Zohar, Sheila Langier, Zvi Ram, Ido Nachmany, Joseph M Klausner, Niv Pencovich
Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28408882/targeted-nanotechnology-in-glioblastoma-multiforme
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
April 10, 2017: Cancer Letters
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