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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/27911279/microrna-101-inhibits-proliferation-migration-and-invasion-of-human-glioblastoma-by-targeting-sox9
#1
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
#2
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
#3
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...
November 8, 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
#4
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
#5
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
#6
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...
October 26, 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
#7
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
#8
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...
October 21, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27764801/foxm1-and-stat3-interaction-confers-radioresistance-in-glioblastoma-cells
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27711187/anti-epidermal-growth-factor-receptor-gene-therapy-for-glioblastoma
#12
Martin J Hicks, Maria J Chiuchiolo, Douglas Ballon, Jonathan P Dyke, Eric Aronowitz, Kosuke Funato, Viviane Tabar, David Havlicek, Fan Fan, Dolan Sondhi, Stephen M Kaminsky, Ronald G Crystal
Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial brain tumor in adults with a mean survival of 14 to 15 months. Aberrant activation of the epidermal growth factor receptor (EGFR) plays a significant role in GBM progression, with amplification or overexpression of EGFR in 60% of GBM tumors. To target EGFR expressed by GBM, we have developed a strategy to deliver the coding sequence for cetuximab, an anti-EGFR antibody, directly to the CNS using an adeno-associated virus serotype rh...
2016: PloS One
https://www.readbyqxmd.com/read/27698790/glioblastoma-multiforme-effect-of-hypoxia-and-hypoxia-inducible-factors-on-therapeutic-approaches
#13
Wen-Juan Huang, Wei-Wei Chen, Xia Zhang
Central nervous system-based cancers have a much higher mortality rate with the 2016 estimates at 6.4 for incidence and 4.3 for deaths per 100,000 individuals. Grade IV astrocytomas, known as glioblastomas are highly aggressive and show a high proliferation index, diffused infiltration, angiogenesis, microvascular proliferation and pleomorphic vessels, resistance to apoptosis, and pseudopalisading necrosis. Extensive hypoxic regions in glioblastomas contribute to the highly malignant phenotype of these tumors...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27693715/cyclooxygenase-2-in-glioblastoma-multiforme
#14
Jiange Qiu, Zhi Shi, Jianxiong Jiang
Glioblastoma multiforme (GBM) represents the most prevalent brain primary tumor, yet there is a lack of effective treatment. With current therapies, fewer than 5% of patients with GBM survive more than 5 years after diagnosis. Mounting evidence from epidemiological studies reveals that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is correlated with reduced incidence of GBM, suggesting that cyclooxygenase-2 (COX-2) and its major product within the brain, prostaglandin E2 (PGE2), are involved in the development and progression of GBM...
September 28, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27679486/identification-of-small-molecule-inhibitors-of-human-cytochrome-c-oxidase-that-target-chemoresistant-glioma-cells
#15
Claudia R Oliva, Tahireh Markert, Larry J Ross, E Lucile White, Lynn Rasmussen, Wei Zhang, Maaike Everts, Douglas R Moellering, Shannon M Bailey, Mark J Suto, Corinne E Griguer
The enzyme cytochrome c oxidase (CcO) or complex IV (EC 1.9.3.1) is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes than those with low tumor CcO activity...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27648359/mir-422a-acts-as-a-tumor-suppressor-in-glioblastoma-by-targeting-pik3ca
#16
Haiqian Liang, Renjie Wang, Ying Jin, Jianwei Li, Sai Zhang
Although surgical treatment, chemotherapy, and radiotherapy have improved the overall survival rate in glioblastoma multiforme (GBM), further intensive research of GBM's molecular mechanism is still needed. In this study, we observed that miR-422a was downregulated in GBM tissues and cell lines by quantitative real-time polymerase chain reaction (PCR) and primer extension assay. Overexpression of miR-422a significantly reduced the cell proliferation, migration, and invasion of GBM cells. Functional study indicated that miR-422a inhibited cell proliferation, invasion, and migration by targeting PIK3CA, an important member of PI3K/Akt signal pathway...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27643505/challenges-in-targeting-a-basic-helix-loop-helix-transcription-factor-with-hydrocarbon-stapled-peptides
#17
Amanda L Edwards, Dimphna H Meijer, Rachel M Guerra, Remco J Molenaar, John A Alberta, Federico Bernal, Gregory H Bird, Charles D Stiles, Loren D Walensky
Basic helix-loop-helix (bHLH) transcription factors play critical roles in organism development and disease by regulating cell proliferation and differentiation. Transcriptional activity, whether by bHLH homo- or heterodimerization, is dependent on protein-protein and protein-DNA interactions mediated by α-helices. Thus, α-helical decoys have been proposed as potential targeted therapies for pathologic bHLH transcription. Here, we developed a library of stabilized α-helices of OLIG2 (SAH-OLIG2) to test the capacity of hydrocarbon-stapled peptides to disrupt OLIG2 homodimerization, which drives the development and chemoresistance of glioblastoma multiforme, one of the deadliest forms of human brain cancer...
October 4, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27633091/her2-targeted-recombinant-protein-immuno-caspase-6-effectively-induces-apoptosis-in-her2-overexpressing-gbm-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#18
Leiming Zhang, Junlin Ren, Hangyu Zhang, Gang Cheng, Yanming Xu, Shuangwu Yang, Chao Dong, Dandong Fang, Jianning Zhang, Angang Yang
Glioblastoma multiforme (GBM), which is associated with a high rate of morbidity and mortality, is among the most malignant and treatment-refractory neoplasms in human adults. As GBM is highly resistant to conventional therapies, immunotherapies are a promising treatment candidate. HER2 is an attractive target for GBM immunotherapy, as its expression is highly associated with various types of GBM. We previously reported that a novel HER2-targeted recombinant protein e23sFv-Fdt-casp6 has an antitumor effect on HER2-positive gastric cancer cells...
September 12, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27630302/mutation-screening-of-her-2-n-ras-and-nf1-genes-in-brain-tumor-biopsies
#19
Christos Yapijakis, Maria Adamopoulou, Konstantina Tasiouka, Costas Voumvourakis, George Stranjalis
BACKGROUND/AIM: A deeper understanding of the complex molecular pathology of brain malignancies is needed in order to develop more effective and targeted therapies of these highly lethal disorders. In an effort to further enlighten the molecular pathology of brain oncogenesis involving the her-2 (erbB-2/neu/ngl)/N-ras/nf1 pathway, we screened the genotypes of specimens from various types of brain tumors. MATERIALS AND METHODS: The studied specimens included 35 biopsies of four general categories: 13 neuroglial tumors (4 astrocytomas, 2 oligodendrogliomas, 7 glioblastomas multiforme), 14 meningiomas, 3 other nervous system tumors (2 schwannomas, 1 craniopharyngioma) and 5 metastatic tumors (such as lung carcinomas and chronic myelocytic leukemia)...
September 2016: Anticancer Research
https://www.readbyqxmd.com/read/27614160/human-tissue-engineering-allows-the-identification-of-active-mirna-regulators-of-glioblastoma-aggressiveness
#20
E Cosset, T Petty, V Dutoit, D Tirefort, P Otten-Hernandez, L Farinelli, P-Y Dietrich, O Preynat-Seauve
Glioblastoma multiforme (GBM) is among the most aggressive cancers associated with massive infiltration of peritumoral parenchyma by migrating tumor cells. The infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with redundant signaling pathways likely underlie the inability of conventional and targeted therapies to achieve long-term remissions. In this respect, microRNAs (miRNAs), which are endogenous small non-coding RNAs that play a role in cancer aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic targets for treatment of malignant gliomas...
November 2016: Biomaterials
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