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Qiyong Jiang, Yimin Liu, Shijuan Zhang, Naikun Li, Gaoling Sun
MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues...
October 17, 2016: Oncotarget
George A Alexiou, Paraskevi Gerogianni, Evrysthenis Vartholomatos, Athanasios P Kyritsis
Glioblastoma is the most malignant primary brain tumor with a median survival of 15 months. Temozolomide (TMZ) is the standard of care for these patients. Iron chelators have been shown to have anti-tumor activity; however, deferiprone (DFP), an orally administered iron chelator, has not been previously evaluated in gliomas. In the present study, we found that combination treatment in glioma cells with TMZ and DFP significantly reduced cell viability, produced cell cycle arrest at G2/M phase, and enhanced apoptosis...
October 21, 2016: Cancer Investigation
Wei Zhang, M Can Gulersonmez, Thomas Hankemeier, Rawi Ramautar
In metabolomics, a wide range of analytical techniques is used for the global profiling of (endogenous) metabolites in complex samples. In this paper, a protocol is presented for the analysis of anionic and cationic metabolites in biological samples by capillary electrophoresis-mass spectrometry (CE-MS). CE is well-suited for the analysis of highly polar and charged metabolites as compounds are separated on the basis of their charge-to-size ratio. A recently developed sheathless interfacing design, i.e., a porous tip interface, is used for coupling CE to electrospray ionization (ESI) MS...
October 1, 2016: Journal of Visualized Experiments: JoVE
S Sengupta, G Mao, Z S Gokaslan, P Sampath
Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment...
October 21, 2016: Cancer Gene Therapy
Mikkel Staberg, Signe Regner Michaelsen, Rikke Darling Rasmussen, Mette Villingshøj, Hans Skovgaard Poulsen, Petra Hamerlik
PURPOSE: Glioblastoma (GBM) ranks among the deadliest solid cancers worldwide and its prognosis has remained dismal, despite the use of aggressive chemo-irradiation treatment regimens. Limited drug delivery into the brain parenchyma and frequent resistance to currently available therapies are problems that call for a prompt development of novel therapeutic strategies. While only displaying modest efficacies as mono-therapy in pre-clinical settings, histone deacetylase inhibitors (HDACi) have shown promising sensitizing effects to a number of cytotoxic agents...
October 20, 2016: Cellular Oncology (Dordrecht)
Rachel Grossman, Nir Shimony, Dror Shir, Tal Gonen, Razi Sitt, Tali Jonas Kimchi, Carmit Ben Harosh, Zvi Ram
BACKGROUND: The extent of tumor resection (EOTR) calculated by enhanced T1 changes in glioblastomas has been previously reported to predict survival. However, fluid-attenuated inversion recovery (FLAIR) volume may better represent tumor burden. In this study, we report the first assessment of the dynamics of FLAIR volume changes over time as a predictive variable for post-resection overall survival (OS). METHODS: Contemporary data from 103 consecutive patients with complete imaging and clinical data who underwent resection of newly diagnosed glioblastoma followed by the Stupp protocol between 2010 and 2013 were analyzed...
October 20, 2016: Annals of Surgical Oncology
Sharon K Michelhaugh, Otto Muzik, Anthony R Guastella, Neil V Klinger, Lisa A Polin, Hancheng Cai, Yanchun Xin, Thomas J Mangner, Shaohui Zhang, Csaba Juhasz, Sandeep Mittal
: Abnormal tryptophan metabolism via the kynurenine pathway (KP) is involved in the pathophysiology of a variety of human diseases including cancers. α-[(11)C]-methyl-L-tryptophan ((11)C-AMT) positron emission tomography (PET) imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of (11)C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan ((18)F-FETrp) may be useful to assess tryptophan metabolism via the KP...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Gina Lee, Brenda Auffinger, Donna Guo, Tanwir Hasan, Marc Deheeger, Alex L Tobias, Jeong Yeon Kim, Fatemeh Atashi, Lingjiao Zhang, Maciej S Lesniak, James C David, Atique U Ahmed
Increasing evidence exposes a subpopulation of cancer cells, known as cancer stem cells (CSCs), to be critical for the progression of several human malignancies, including glioblastoma multiforme (GBM). CSCs are highly tumorigenic, capable of self-renewal, and resistant to conventional therapies, and thus considered to be one of the key contributors to disease recurrence. In order to elucidate the poorly understood evolutionary path of tumor recurrence and the role of CSCs in this process, we developed patient-derived xenograft GBM recurrent models induced by anti-glioma chemotherapy, temozolomide (TMZ)...
October 7, 2016: Molecular Cancer Therapeutics
Nasser K Yaghi, Jun Wei, Yuuri Hashimoto, Ling-Yuan Kong, Konrad Gabrusiewicz, Edjah K Nduom, Xiaoyang Ling, Neal Huang, Shouhao Zhou, Brittany C Parker Kerrigan, Jonathan M Levine, Virginia R Fajt, Gwendolyn Levine, Brian F Porter, Eric G Marcusson, Kiyoshi Tachikawa, Padmanabh Chivukula, David C Webb, Joseph E Payne, Amy B Heimberger
BACKGROUND: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases. METHODS: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects...
October 8, 2016: Neuro-oncology
J P Cata, K B Hagan, S D O Bhavsar, R Arunkumar, R Grasu, A Dang, R Carlson, B Arnold, Y Potylchansky, I Lipski, T McHugh, F Jimenez, A T Nguyen, L Feng, T F Rahlfs
BACKGROUND: Several studies have examined the impact of anesthetics on cancer recurrence. Isoflurane but not desflurane has protumoral effects. We hypothesize the use of isoflurane but not desflurane during surgery for primary GBM is an independent predictor of disease progression and mortality. METHODS: 378 adult patients were included in the study. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5years were compared in patients who had either desflurane or isoflurane alone or in combination with propofol infusion...
October 17, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Rebecca J Hron, Branko S Jursic, Donna M Neumann
Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (ClogP), acidic strength (calculated pKa), and polar surface area (PSA) were used to design a diverse structural library of these compounds...
October 4, 2016: Bioorganic & Medicinal Chemistry
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
Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Weijie Li, Shicai Dong, Wei Wei, Guangxiu Wang, Anling Zhang, Peiyu Pu, Zhifan Jia
The transcriptional coactivator with PDZ-binding motif (TAZ) is one of the important downstream effectors of Hippo pathway. In this study, the potential implication of TAZ in gliomagenesis was explored. TAZ expression was identified to be upregulated in glioma specimens and positively correlated with tumor grade. Meanwhile, its expression in nucleus was increased more significantly with the ascending order of tumor grade. Knocking down TAZ inhibited glioma cell proliferation, invasion and promoted apoptosis...
October 13, 2016: Oncotarget
Hailong Li, Jiye Li, Gang Cheng, Jianning Zhang, Xuezhen Li
PURPOSE: This study aimed to investigate the potential association between IDH mutation and O(6)-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy. METHODS: A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis...
October 12, 2016: Clinical Neurology and Neurosurgery
Zuriñe Antón, Ane Landajuela, Javier H Hervás, L Ruth Montes, Sonia Hernández-Tiedra, Guillermo Velasco, Felix M Goñi, Alicia Alonso
The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP...
October 20, 2016: Autophagy
Pelin Erkoc, Ahmet Cingöz, Tugba Bagci Onder, Seda Kizilel
Overcoming drug resistance is a major challenge for cancer therapy. Tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL) is a potent therapeutic as an activator of apoptosis, particularly in tumor but not in healthy cells. However, its efficacy is limited by the resistance of tumor cell populations to the therapeutic substance. Here, we have addressed this limitation through the development of a controlled release system, matrix-metalloproteinase (MMP)-sensitive and arg-gly-asp-ser (RGDS) peptide functionalized poly (ethylene-glycol) (PEG) particles which are synthesized via visible-light-induced water-in-water emulsion polymerization...
October 20, 2016: Macromolecular Bioscience
Shigeo Ohba, Yuichi Hirose
Glioblastomas are the most aggressive of all gliomas and have the worst prognosis, with 5-year survival rates of less than 10%. Temozolomide (TMZ) is a DNA-methylating agent. Now that TMZ is available, the standard treatment is to resect as much of the tumor as possible without inducing unacceptable neurologic deficits, followed by treatment with radiation and TMZ. TMZ has also been used for maintenance therapy. Recently, bevacizumab, which is a monoclonal antibody to vascular endothelial growth factor, has been used for the initial treatment of glioblastomas and for the treatment of recurrent glioblastomas...
October 14, 2016: Current Medicinal Chemistry
Zhangjing Yang, Piaopiao Feng, Tian Wen, Minghua Wan, Xunning Hong
Differentiation of glioblastoma multiformes (GBMs) and lymphomas using multi-sequence magnetic resonance imaging (MRI) is an important task that is valuable for treatment planning. However, this task is a challenge because GBMs and lymphomas may have a similar appearance in MRI images. This similarity may lead to misclassification and could affect the treatment results. In this paper, we propose a semi-automatic method based on multi-sequence MRI to differentiate these two types of brain tumors. Our method consists of three steps: 1) the key slice is selected from 3D MRIs and region of interests (ROIs) are drawn around the tumor region; 2) different features are extracted based on prior clinical knowledge and validated using a t-test; and 3) features that are helpful for classification are used to build an original feature vector and a support vector machine is applied to perform classification...
October 18, 2016: CNS & Neurological Disorders Drug Targets
Kara W Moyes, Nicole Ap Lieberman, Shannon A Kreuser, Harrison Chinn, Conrad Winter, Gail Deutsch, Virginia Hoglund, Reid Watson, Courtney A Crane
In spite of their successes against hematologic malignancies, immunotherapeutic interventions for the treatment of patients with glioblastoma (GBM) have thus far been unsuccessful. This is in part due to the presence of a tumor microenvironment that fosters neoplastic growth and protects the tumor from destruction by the immune system. We have developed a novel genetically engineered macrophage-based platform with the potential to minimize the effects of the suppressive tumor microenvironment and improve innate and adaptive anti-tumor immune responses...
October 19, 2016: Human Gene Therapy
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