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Glioma AND iron

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
Jin Hee Kim, Ji-Yeon Suh, Dong-Cheol Woo, Yu Sub Sung, Woo-Chan Son, Yoon Seok Choi, Sang Joon Pae, Jeong Kon Kim
Contrast enhancement by an extracellular-fluid contrast agent (CA) (Gd-DOTA) depends primarily on the blood-brain-barrier permeability (bp), and transverse-relaxation change caused by intravascular T2 CA (superparamagnetic iron oxide nanoparticles, SPIONs) is closely associated with the blood volume (BV). Pharmacokinetic (PK) vascular characterization based on single-CA-using dynamic contrast-enhanced MRI (DCE-MRI) has shown significant measurement variation according to the molecular size of the CA. Based on this recognition, this study used a dual injection of Gd-DOTA and SPIONs for tracing the changes of bp and BV in C6 glioma growth (Days 1 and 7 after the tumor volume reached 2 mL)...
October 10, 2016: NMR in Biomedicine
Jessica K R Boult, Marco Borri, Alexa Jury, Sergey Popov, Gary Box, Lara Perryman, Suzanne A Eccles, Chris Jones, Simon P Robinson
High grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co-option in regions of invasive growth (in which the blood-brain barrier remains intact) and neoangiogenesis is a major challenge faced in the assessment of brain tumours by conventional MRI. A multiparametric MRI approach, incorporating native measurements and both Gd-DTPA (Magnevist) and ultrasmall superparamagnetic iron oxide (P904)-enhanced imaging, was used in combination with histogram and unsupervised cluster analysis using a k-means algorithm to examine the spatial distribution of vascular parameters, water diffusion characteristics and invasion in intracranially propagated rat RG2 gliomas and human MDA-MB-231 LM2-4 breast adenocarcinomas in mice...
September 27, 2016: NMR in Biomedicine
Xueqin Wang, Miaomiao Tu, Baoming Tian, Yanjie Yi, ZhenZhen Wei, Fang Wei
Superparamagnetic iron oxide nanoparticles (SPIO NPs), utilized as carriers are attractive materials widely applied in biomedical fields, but target-specific SPIO NPs with lower toxicity and excellent biocompatibility are still lacking for intracellular visualization in human brain tumor diagnosis and therapy. Herein, bovine serum albumin (BSA) coated superparamagnetic iron oxide, i.e. γ-Fe2O3 nanoparticles (BSA-SPIO NPs), are synthesized. Tumor-specific ligand folic acid (FA) is then conjugated onto BSA-SPIO NPs to fabricate tumor-targeted NPs, FA-BSA-SPIO NPs as a contrast agent for MRI imaging...
November 1, 2016: Analytical Biochemistry
Sophie Richard, Ana Saric, Marianne Boucher, Christian Slomianny, Françoise Geffroy, Sébastien Mériaux, Yoann Lalatonne, Patrice X Petit, Laurence Motte
Gliomas are the most common primary brain tumor in humans. To date, the only treatment of care consists of surgical removal of the tumor bulk, irradiation, and chemotherapy, finally resulting in a very poor prognosis due to the lack of efficiency in diagnostics. In this context, nanomedicine combining both diagnostic and magnetic resonance imaging (MRI) and therapeutic applications is a relevant strategy referred to theranostic. Magnetic nanoparticles (NP) are excellent MRI contrast agents because of their large magnetic moment, which induces high transverse relaxivity (r2) characteristic and increased susceptibility effect (T2*)...
October 21, 2016: ACS Chemical Biology
Zhiguang Pan, Zhifeng Shi, Hua Wei, Fengyan Sun, Jianping Song, Yongyi Huang, Te Liu, Ying Mao
Glioma stem cells belong to a special subpopulation of glioma cells that are characterized by strong proliferation, invasion and drug resistance capabilities. Magnetic nanoparticles are nanoscale biological materials with magnetic properties. In this study, CD133(+) primary glioma stem cells were isolated from patients and cultured. Then, magnetic nanoparticles were used to mediate the transfection and expression of a microRNA-374a overexpression plasmid in the glioma stem cells. Transmission electron microscopy detected the presence of significant magnetic nanoparticle substances within the CD133(+) glioma stem cells after transfection...
2016: Journal of Cancer
Lingyun Zhao, Yajing Zheng, Hao Yan, WenSheng Xie, Xiaodan Sun, Ning Li, Jintian Tang
Superparamagnetic iron oxide nanoparticles (SPIONs) with appropriate surface chemistry have attracted wild attention in medical and biological application because of their current and potential usefulness such as magnetic resonance imaging (MRI) contrast enhancement, magnetic mediated hyperthermia (MMH), immunoassay, and in drug delivery, etc. In this study, we investigated the MRI contrast agents and MMH mediators properties of the novel 2-deoxy-D-glucose (2-DG) modified SPIONs. As a non-metabolizable glucose analogue, 2-DG can block glycolysis and inhibits protein glycosylation...
March 2016: Journal of Nanoscience and Nanotechnology
Ching-Hsiang Fan, Yu-Hang Cheng, Chien-Yu Ting, Yi-Ju Ho, Po-Hung Hsu, Hao-Li Liu, Chih-Kuang Yeh
One of the greatest challenges in the deployment of chemotherapeutic drugs against brain tumors is ensuring that sufficient drug concentrations reach the tumor, while minimizing drug accumulation at undesired sites. Recently, injection of therapeutic agents following blood-brain barrier (BBB) opening by focused ultrasound (FUS) with microbubbles (MBs) has been shown to enhance drug delivery in targeted brain regions. Nevertheless, the distribution and quantitative deposition of agents delivered to the brain are still hard to estimate...
2016: Theranostics
Joanne M Kingsbury, Nachiketha Shamaprasad, R Blake Billmyre, Joseph Heitman, Maria E Cardenas
A major advance in understanding the progression and prognostic outcome of certain cancers, such as low-grade gliomas, acute myeloid leukemia, and chondrosarcomas, has been the identification of early-occurring mutations in the NADP(+)-dependent isocitrate dehydrogenase genes IDH1 and IDH2 These mutations result in the production of the onco-metabolite D-2-hydroxyglutarate (2HG), thought to contribute to disease progression. To better understand the mechanisms of 2HG pathophysiology, we introduced the analogous glioma-associated mutations into the NADP(+) isocitrate dehydrogenase genes (IDP1, IDP2, IDP3) in Saccharomyces cerevisiae Intriguingly, expression of the mitochondrial IDP1(R148H) mutant allele results in high levels of 2HG production as well as extensive mtDNA loss and respiration defects...
July 17, 2016: Human Molecular Genetics
He-Lin Xu, Kai-Li Mao, Yin-Ping Huang, Jing-Jing Yang, Jie Xu, Pian-Pian Chen, Zi-Liang Fan, Shuang Zou, Zheng-Zheng Gao, Jia-Yu Yin, Jian Xiao, Cui-Tao Lu, Bao-Lin Zhang, Ying-Zheng Zhao
Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX...
August 7, 2016: Nanoscale
Esther Kneepkens, Adriana Fernandes, Klaas Nicolay, Holger Grüll
OBJECTIVES: Drug-loaded temperature-sensitive liposomes (TSLs) allow heat-triggered local drug delivery to tumors. When magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is applied to heat up the tumor, corelease of a drug together with an MR contrast agent (CA) from TSLs allows for indirect imaging of the drug release with MR imaging. However, liposomal encapsulation of commonly used gadolinium (Gd)-based MR CAs leads to prolonged retention times in the liver and spleen, which could lead to a transmetallation and redistribution of Gd to other organs...
June 15, 2016: Investigative Radiology
Karin Pernet-Gallay, Pierre-Henri Jouneau, Anne Bertrand, Julie Delaroche, Régine Farion, Chantal Rémy, Emmanuel L Barbier
This study evaluates the extravasation pathways of circulating macromolecules in a rat glioma model (RG2) which was observed by both magnetic resonance imaging using ultrasmall superparamagnetic iron oxide and electron microscopy. Although magnetic resonance imaging signal enhancement was observed as soon as 10 min after injection (9.4% 2 h after injection), electron microscopy showed that endothelial cells were still tightly sealed. However, circulating immunoglobulin G and ultrasmall superparamagnetic iron oxide were found in large membrane compartments of endothelial cells, in the basal lamina (7...
June 15, 2016: Journal of Cerebral Blood Flow and Metabolism
Maxim A Shevtsov, Gabriele Multhoff
Glioblastoma multiforme one of the most aggressive brain tumors has a very poor clinical outcome. Despite the introduction of the alkylating reagent temozolomide (TMZ) to surgery and radiotherapy the survival of patients could only be modestly increased up to less than 15 months. Therefore, innovative treatment strategies are urgently needed to improve survival of glioma patients. Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted a lot of attention due to their widespread diagnostic and therapeutic applications in neuro-oncology...
June 7, 2016: Current Drug Metabolism
Kan Fang, Peifeng Liu, Suyan Dong, Yanjie Guo, Xinxin Cui, Xiaoying Zhu, Xuan Li, Lianghan Jiang, Te Liu, Yuncheng Wu
Glioma stem cells (GSCs) are a special subpopulation of glioma cells that are key to the sensitivity of tumors to treatments and to the possibility of tumor recurrence. Identifying new strategies that inhibit the growth of GSCs are therefore important for developing novel therapies for glioblastoma multiforme (GBM). In this study, CD133+ human glioma stem cells were isolated and cultured. Magnetic nanoparticles were used to mediate the expression of siRNAs targeting the HOTAIR (si-HOTAIR) sequence in human gliomas...
August 2016: International Journal of Oncology
Marina Radoul, Limor Lewin, Batya Cohen, Roni Oren, Stanislav Popov, Geula Davidov, Moriel H Vandsburger, Alon Harmelin, Ronit Bitton, Jean-Marc Greneche, Michal Neeman, Raz Zarivach
Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene - ferritin-M6A - in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation...
2016: Scientific Reports
Binhua Luo, Siqi Wang, Rong Rao, Xuhan Liu, Haibo Xu, Yun Wu, Xiangliang Yang, Wei Liu
The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting...
December 2016: Nanoscale Research Letters
Heng Liu, Jun Zhang, Xiao Chen, Xue-Song Du, Jin-Long Zhang, Gang Liu, Wei-Guo Zhang
Gliomas are the most common primary brain tumors and have a very dismal prognosis. However, recent advancements in nanomedicine and nanotechnology provide opportunities for personalized treatment regimens to improve the poor prognosis of patients suffering from glioma. This comprehensive review starts with an outline of the current status facing glioma. It then provides an overview of the state-of-the-art applications of iron oxide nanoparticles (IONPs) to glioma diagnostics and therapeutics, including MR contrast enhancement, drug delivery, cell labeling and tracking, magnetic hyperthermia treatment and magnetic particle imaging...
April 21, 2016: Nanoscale
Meric Adil Altinoz, Ilhan Elmaci, Bahri Ince, Aysel Ozpinar, Aydin Murat Sav
In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS)...
May 2016: Journal of Neurological Surgery. Part A, Central European Neurosurgery
Juan Zhang, Ning Chen, Hao Wang, Wei Gu, Kang Liu, Penghui Ai, Changxiang Yan, Ling Ye
A major limit of superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic resonance (MR) imaging nanoprobe in clinical applications is that the SPIONs are unable to reach sufficient concentrations at the tumor site by passive targeting to produce an obvious contrast effect for tumor imaging. Single-targeting SPIONs systems have been applied to improve the contrast effect. However, they still suffer from a lack of efficiency and specificity of the SPIONs to tumors. Herein, we developed folic acid (FA) and cyclic Arg-Gly-Asp-D-Tyr-Lys (c(RGDyK)) dual-targeting nanoprobes based on Cy5...
May 1, 2016: Journal of Colloid and Interface Science
Tingfeng Wu, Yuntao Li, Baohui Liu, Shenqi Zhang, Liquan Wu, Xiaonan Zhu, Qianxue Chen
Accumulating evidence suggests that iron-associated proteins contribute to tumor initiation and development. Ferritin light chain (FTL), a key protein in iron metabolism, is associated with the survival of glioblastoma multiforme (GBM) patients; however, the molecular mechanisms underlying this association remain largely unclear. Therefore, in the present study, we investigated the role of FTL in the pathogenesis of GBM. By using quantitative real-time RT-PCR, we found that expression of FTL was higher in patients with GBM than in those with low-grade glioma...
2016: PloS One
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