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Yuzuki Kanda, Miho Okada, Rina Ikarashi, Eri Morioka, Takashi Kondo, Masayuki Ikeda
Clozapine (Clz) and olanzapine (Olz) are second generation (atypical) antipsychotics, used widely for treating schizophrenia and bipolar disorder. These drugs share multiple sites of actions, however their mechanisms remain incompletely understood. Here, we analyzed the effects of these drugs on primary cultures of rat cortical astrocytes and C6 glioma cells using fura-2-based Ca(2+) imaging. C6 cells, but not cortical astrocytes, express the serotonin 2A receptor subtype, which couples to phospholipase C. Clz (1μM) significantly blocked serotonin-induced Ca(2+) transients in C6 cells, consistent with known antagonistic actions of Clz...
October 18, 2016: Neuroscience Letters
Dorimar Stiz, Adriana Campos, Ana Lúcia Tasca Gois Ruiz, João Ernesto de Carvalho, Rogério Corrêa, Valdir Cechinel-Filho
This work describes the antiproliferative potential of 14 cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against several human cancer cell lines. The antiproliferative effect was evaluated using the sulforhodamine B assay. Although some compounds from methylphtalimide and carboxylic acid phtalimide classes exhibited a selective antiproliferative activity, the itaconimides (11-14) exhibited the best results, especially compound 14, which presented a TGI (concentration that produces total growth inhibition) value of 0...
October 21, 2016: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
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
Stefanie Bette, Jens Gempt, Thomas Huber, Claire Delbridge, Bernhard Meyer, Claus Zimmer, Jan S Kirschke, Tobias Boeckh-Behrens
OBJECTIVE Recent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients. METHODS A total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study...
October 21, 2016: Journal of Neurosurgery
Ulysse Gimenez, Hélène Lajous, Michèle El Atifi, Marie Bidart, Vincent Auboiroux, Pascal Henry Fries, François Berger, Hana Lahrech
Cellular MRI, which visualizes magnetically labelled cells (cells*), is an active research field for in vivo cell therapy and tracking. The simultaneous relaxation rate measurements (R2 *, R2 , R1 ) are the basis of a quantitative cellular MRI method proposed here. U937 cells were labelled with Molday ION Rhodamine B, a bi-functional superparamagnetic and fluorescent nanoparticle (U937*). U937* viability and proliferation were not affected in vitro. In vitro relaxometry was performed in a cell concentration range of [2...
October 21, 2016: Contrast Media & Molecular Imaging
Chao Shang, Yan Guo, Yang Hong, Yi-Xue Xue
Tumour suppressor candidate 7 (TUSC7) is a novel tumor suppressor gene generating long non-coding RNA (lncRNAs) in several types of human cancers. The expression and function of TUSC7 in human brain glioma has yet to be elucidated. In this study, TUSC7 was poorly expressed in tissues and cell lines of glioma, and the lower expression was correlated with glioma of the worse histological grade. Moreover, TUSC7 is a prognostic biomarker of glioma patients. Up-regulation of TUSC7 suppressed cellular proliferation and invasion of glioma cells, and accelerated cellular apoptosis...
2016: Frontiers in Cellular Neuroscience
Ling Qi, Hongquan Yu, Yu Zhang, Donghai Zhao, Peng Lv, Yue Zhong, Ye Xu
M2 tumor-associated macrophage has been found to play a supportive role in the progression of glioma. The underlying mechanism, nevertheless, has been largely unknown. In our study, to investigate how M2 macrophage played role in glioma, firstly we've analyzed the clinicopathological significance of M2 macrophage existence on clinical tissues of glioma using detection of CD163 expression with immunohistochemistry. Then, we've artificially induced M2 macrophage from human monocyte cell line THP-1, followed by co-culture with glioma cell lines in vitro...
September 28, 2016: Oncotarget
Ying Li, Xuemin Zheng, Min Gong, Jianning Zhang
The challenge of effectively delivering therapeutic agents to the brain has created an entire field of active research devoted to overcoming the blood brain barrier (BBB) and efficiently delivering drugs to the brain. Angiopep-2 can trigger transcytosis and traverse the BBB by recognizing low-density lipoprotein related protein-1 (LRP-1) expressed on the brain capillary endothelial cells. Here, we designed a novel strategy for the delivery of drugs to the brain. The novel drug delivery system was a combination of a receptor-targeting ligand, such as low-density lipoprotein related protein 1, and a cell-penetrating peptide (CPP)...
October 17, 2016: Oncotarget
Marc Jansen, Sophie Em Veldhuijzen van Zanten, Dannis G Van Vuurden, Marc Huisman, Danielle J Vugts, Otto S Hoekstra, Guus A M S van Dongen, Gert-Jan Jl Kaspers
: Predictive tools to guide therapy in children with brain tumors are urgently needed. We introduced molecular imaging to facilitate this. We investigated whether bevacizumab can reach the tumor in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of zirconium-89((89)Zr)-labeled bevacizumab by PET. In addition we evaluated the safety of the procedure in children and determined the optimal timing of imaging. METHODS: Patients received 0...
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
Zhao-Hui Wang, Xia-Qing Guo, Qi-Shun Zhang, Jian-Lei Zhang, Yan-Li Duan, Guo-Fei Li, Dong-Lin Zheng
BACKGROUND AND AIM: Long non-coding RNAs have been confirmed to play a critical role in various cancers. In the present study, the effect of long non-coding RNA (lncRNA) CCAT1 on glioma cell proliferation and its potential mechanism were investigated. METHODS AND RESULTS: Real-time PCR results showed that lncRNA-CCAT1 expression was significantly upregulated in glioma cancer tissues and cell lines compared with controls. After inhibiting CCAT1 expression in glioma cell line U251 with siRNA-CCAT1 (si-CCAT1), the cell viability and cell colony formation were decreased, the cell cycle was arrested in G1 phase, and the cell apoptosis was increased...
October 17, 2016: Biochemical and Biophysical Research Communications
Jie Tao, Jiumeng Zhang, Yu Hu, Yuan Yang, Zhiyuan Gou, Ting Du, Jian Mao, Maling Gou
Conventional surgical methods can not completely remove the tumor cells, and an inevitable recurrence always results in death. In this study, we prepared a conformal hydrogel nanocomposite with potential to inhibit the recurrence of glioma. Based on the MRI of a patient's brain tumor cavity (BTC), we 3D-printed a mould for preparing the customized implants that could match the resection cavity. The obtained macroporous hydrogel, containing paclitaxel (PTX) nanoparticles, could sustained release PTX. From the confocal microscopy image, we could detect that the hydrogel nanocomposite combined with nanoparticles uniformly...
October 21, 2016: Journal of Biomaterials Science. Polymer Edition
Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 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
Wen Wang, Fan Yang, Lu Zhang, Jing Chen, Zheng Zhao, Haoyuan Wang, Fan Wu, Tingyu Liang, Xiaoyan Yan, Jiye Li, Qing Lan, Jiangfei Wang, Jizong Zhao
Anaplastic glioma is Grade III and the median overall survival is about 37.6 months. However, there are still other factors that affect the prognosis for anaplastic glioma patients due to variable overall survival. So we screened four-lncRNA signature (AGAP2-AS1, TPT1-AS1, LINC01198 and MIR155HG) from the lncRNA expression profile from the GSE16011, CGGA and REMBRANDT datasets. The patients in low risk group had longer overall survival than high risk group (median OS 2208.25 vs. 591.30 days; P < 0.0001)...
October 13, 2016: Oncotarget
M Paradowski, M Bilinska, J Bar
The biological features of glioma cells may define their clinical outcome. Little is known about the interactions between KAI1/CD82 metastatic suppressor protein and PDGFR in gliomas. The aim of the study was to examine KAI1/CD82 and PDGFR expression in gliomas in order to find the impact of these proteins on progression of the tumors. PDGFR, KAI1/CD82 protein expression and mRNA of genes were evaluated on eighty four paraffin-embedded tissue of gliomas using immunohistochemical staining and RT-PCR analysis...
2016: Folia Neuropathologica
K Bilmin, T Kujawska, W Secomski, A Nowicki, P Grieb
Sonodynamic therapy (SDT) is a promising technique based on the ability of certain substances, called sonosensitizers, to sensitize cancer cells to non-thermal effects of low-energy ultrasound waves, allowing their destruction. Sonosensitization is thought to induce cell death by direct physical effects such as cavitation and acoustical streaming as well as by complementary chemical reactions generating oxygen free radicals. One of the promising sonosensitizers is 5-aminolevulinic acid (ALA) which upon selective uptake by cancer cells is metabolized and accumulated as protoporphyrin IX...
2016: Folia Neuropathologica
E Matyja, W Grajkowska, K Stępień, E Naganska
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection...
2016: Folia Neuropathologica
Qiao-Li Lv, Yuan-Tao Huang, Gui-Hua Wang, Yan-Ling Liu, Jin Huang, Qiang Qu, Bao Sun, Lei Hu, Lin Cheng, Shu-Hui Chen, Hong-Hao Zhou
Emerging studies show that dysregulation of the receptor of activated protein kinase C1 (RACK1) plays a crucial role in tumorigenesis and progression of various cancers. However, the biological function and underlying mechanism of RACK1 in glioma remains poorly defined. Here, we found that RACK1 was significantly up-regulated in glioma tissues compared with normal brain tissues, being closely related to clinical stage of glioma both in mRNA and protein levels. Moreover, Kaplan-Meier analysis demonstrated that patients with high RACK1 expression had a poor prognosis (p = 0...
October 18, 2016: International Journal of Environmental Research and Public Health
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