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Juan Carlos González-Orozco, Valeria Hansberg-Pastor, Paulina Valadez-Cosmes, Walter Nicolas-Ortega, Yenifer Bastida-Beristain, Marisol De La Fuente-Granada, Aliesha González-Arenas, Ignacio Camacho-Arroyo
BACKGROUND AND AIMS: Glioblastoma is the most frequent and aggressive brain tumor due to its high capacity to migrate and invade normal brain tissue. The steroid hormone progesterone (P4) contributes to the progression of glioblastoma by promoting proliferation, migration, and cellular invasion through the activation of its intracellular receptor (PR). However, the use of PR antagonist RU486 partially blocks the effects of P4, suggesting the participation of signaling pathways such as those mediated by membrane receptors to P4 (mPRs)...
June 9, 2018: Molecular and Cellular Endocrinology
Mohammed Khurshed, Niels Aarnoudse, Renske Hulsbos, Vashendriya V V Hira, Hanneke W M van Laarhoven, Johanna W Wilmink, Remco J Molenaar, Cornelis J F van Noorden
Isocitrate dehydrogenase ( IDH1)-1 is mutated in various types of human cancer, and the presence of this mutation is associated with improved responses to irradiation and chemotherapy in solid tumor cells. Mutated IDH1 (IDH1MUT ) enzymes consume NADPH to produce d-2-hydroxyglutarate (d-2HG) resulting in the decreased reducing power needed for detoxification of reactive oxygen species (ROS), for example. The objective of the current study was to investigate the mechanism behind the chemosensitivity of the widely-used anticancer agent cisplatin in IDH1MUT cancer cells...
June 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Song Yang, Xiuping Chen, Shengli Li, Bin Sun, Chunhua Hang
BACKGROUND A mouse model of subarachnoid hemorrhage (SAH) investigated the effects of melatonin treatment on the generation of reactive oxygen species (ROS) and the activation of the SIRT3 gene in early brain injury (EBI). MATERIAL AND METHODS Male C57BL/6J mice were assigned to three groups: the SAH group; the sham group; and the SAH + melatonin-treated group (intraperitoneal dose, 150 mg/kg). TUNEL was used to study apoptosis of neuronal cells, Western-blot and immunohistochemistry detected expression of Sirt3, Bcl-2, superoxide dismutase 2 (SOD2), Bax, and cleaved caspase-3...
June 6, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Sebastian Rubino, Martin D Bach, Alexandra L Schober, Ian H Lambert, Alexander A Mongin
Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Ubiquitously expressed volume-regulated anion channels (VRAC) are thought to play a role in cell proliferation, migration, and apoptosis. VRAC are heteromeric channel complexes assembled from proteins belonging to the leucine-rich repeat-containing 8A (LRRC8A through E), among which LRRC8A plays an indispensable role. In the present work, we used an RNAi approach to test potential significance of VRAC and LRRC8A in GBM survival and sensitivity to chemotherapeutic agents...
2018: Frontiers in Oncology
Changjiang Yin, Pibao Li
In cancer research, autophagy has been revealed as one of the major ways to maintain the metabolism of cancer cells, including glioma cells, through protein degradation. Meanwhile, autophagy is also regarded as a kind of mechanism to protect glioma cells from a harmful stimulus, such as chemical and radiation treatment. So, the inhibition of autophagy may be very helpful in curing glioma. This study aimed to determine the effect of autophagic inhibition on glioma cells using tubacin, a specific inhibitor of histone deacetylase 6(HDAC6)...
2018: Open Medicine (Warsaw, Poland)
Yulin Wang, Gefei Guan, Wen Cheng, Yang Jiang, Fengping Shan, Anhua Wu, Peng Cheng, Zongze Guo
BACKGROUND: Glioma is the most common primary brain tumor in adults with a poor prognosis. As a member of ARF subfamily GTPase, ARL2 plays a key role in regulating the dynamics of microtubules and mitochondrial functions. Recently, ARL2 has been identified as a prognostic and therapeutic target in a variety range of malignant tumors. However, the biological functional role of ARL2 in glioma still remains unknown. The aim of this study was to explore the expression and functional role of ARL2 in glioma...
May 29, 2018: BMC Cancer
Fei Peng, Xiaoxiong Wang, Mengting Shu, Mingfei Yang, Ligang Wang, Zhongrui Ouyang, Chen Shen, Xu Hou, Boyan Zhao, Xinzhuang Wang, Linda Wei Zhang, Yaohua Liu, Shiguang Zhao
BACKGROUND/AIMS: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. METHODS: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining...
May 25, 2018: Cellular Physiology and Biochemistry
Jing Xu, He Huang, Renjun Peng, Xiping Ding, Bing Jiang, Xianrui Yuan, Jian Xi
Temozolomide (TMZ) is one of the most commonly used drugs for the clinical treatment of glioblastomas. However, it has been reported that treatment with TMZ can induce autophagy, which leads to tumor resistance and increases the survival of tumor cells. MicroRNA-30a (miR-30a) has been found to have inhibitory effects on autophagy by directly targeting beclin 1. However, the exact role of miR-30a in TMZ-treated glioblastoma cells has not been studied previously. The present study aimed to investigate whether miR-30a increased the cytotoxicity of TMZ to glioblastoma U251 cells, as well as the underlying mechanism...
June 2018: Experimental and Therapeutic Medicine
Chao Liu, Ligang Wang, Hongmei Qiu, Qing Dong, Yong Feng, Dawei Li, Chengli Li, Cundong Fan
Radioactive 125 I seeds-based radiotherapy has achieved great success in treatment of human cancers. However, radioresistance and severe side effects badly limited its clinic application. Recently, chemoradiotherapy as a superior strategy has been rapidly developed and widely used in clinic. However, the underlying mechanism remains elusive. Herein, in the present study, a combined chemoradiation model of 125 I seeds and salinomycin (SAL) in vitro and in vivo was designed, and the enhanced anticancer efficiency and mechanism were also evaluated in human glioma...
May 26, 2018: Neurochemical Research
Man Xiao, Yang An, Fengling Wang, Chao Yao, Chu Zhang, Junfang Xin, Yongjian Duan, Xiaofang Zhao, Na Fang, Shaoping Ji
PTEN, a well-known tumor suppressor, dephosphorylates PIP3 and inhibits AKT activity. A translational variant of PTEN has been identified and termed PTEN-Long (PTEN-L). The additional 173 amino acids (PTEN-L leader) at the N-terminal constitute a potential signal peptide. Differing from canonical PTEN, PTEN-L is secreted into the extracellular fluid and re-enters recipient cells, playing the similar roles as PTEN in vivo and in vitro. This character confers the PTEN-L a therapeutic ability via directly protein delivering instead of traditional DNA and RNA vector options...
May 23, 2018: Experimental Cell Research
Yunsheng Zhang, Guishan Jin, Junwen Zhang, Ruifang Mi, Yiqiang Zhou, Wenhua Fan, Sen Cheng, Wenjie Song, Bo Zhang, Mengjiao Ma, Fusheng Liu
Hypoxia is common in Glioblastoma (GBM). By regulating the 'hypoxia signaling cascade', hypoxia affects several processes including cell proliferation, invasion, and angiogenesis. Some studies have revealed that signal transducer and activator of transcription (STAT), including STAT1, is abnormal under hypoxia in several cancers. Here, we investigated the role of STAT1 under hypoxia in glioma progression. We found that STAT1 was downregulated under a hypoxic condition in U251 and U373. STAT1 overexpression can not only decrease proliferation, migration and invasion in U251 and U373 but also inhibit tube formation of HBMECs...
May 22, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hengyi Fan, Raorao Yuan, Shiqi Cheng, Kun Xiong, Xingen Zhu, Yan Zhang
BACKGROUND: Glioma is the most common cause of cancer-related death. Therapy based on radiation seemed to effectively, while the radioresistance of several glioblastoma cells abolished the therapy. Thus, to employ the potential mechanism underlying the radioresistance is essential for glioma treatment. METHODS: Radioresistant cells were constructed using the X-ray radiation. Cell viability and apoptosis were detect using CCK-8 and Annexin-V/propidium iodide (PI), respectively...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Maria Ricci, Francesco Ragonese, Beatrice Gironi, Marco Paolantoni, Assunta Morresi, Loredana Latterini, Bernard Fioretti, Paola Sassi
Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor characterized by highly heterogeneous subpopulations. In order to reveal the heterogeneous cell response, single cell analysis is an essential requirement. In this study, optical microscopy and Raman microspectroscopy were used to follow the stress response of U251 single cells adherent on a silicon substrate. Cultured cells on silicon substrate were treated with hydrogen peroxide to promote apoptosis. Under these conditions expected changes occurred after a few hours and were revealed by the reduction of cytochrome c, lipid, nucleic acid and protein Raman signals: this ensured the possibility to analyse U251 cell line as grown on Si substrate, and to monitor the response of single cells to stress conditions...
May 22, 2018: Scientific Reports
Javier Frontiñán-Rubio, Raquel María Santiago-Mora, Consuelo María Nieva-Velasco, Gustavo Ferrín, Alicia Martínez-González, María Victoria Gómez, María Moreno, Julia Ariza, Eva Lozano, Jacinto Arjona-Gutiérrez, Antonio Gil-Agudo, Manuel De la Mata, Milica Pesic, Juan Ramón Peinado, José M Villalba, Luis Pérez-Romasanta, Víctor M Pérez-García, Francisco J Alcaín, Mario Durán-Prado
OBJECTIVES: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. MATERIAL AND METHODS: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2 - ) and H2 O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time...
May 18, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Yu-Xiao Liu, Wen-Jia Liu, Hui-Ru Zhang, Zhi-Wen Zhang
Background: Many reports have indicated that the intravenous administration of bevacizumab produces a number of systemic side effects. Therefore, we investigated the therapeutic effects of intratumoral bevacizumab administration using a glioma animal model. Methods: The glioma cell lines U251 and U87 that carried luciferase were implanted into the brains of mice to develop glioma models. Glioma-bearing mice were treated with bevacizumab intravenously or intratumorally by Alzet micro-osmotic pumps, and the survival time of mice was monitored...
2018: OncoTargets and Therapy
Rui Liu, Xing-Ping Qin, Yang Zhuang, Ya Zhang, Hua-Bao Liao, Jun-Chun Tang, Meng-Xian Pan, Fei-Fei Zeng, Yang Lei, Rui-Xue Lei, Shu Wang, An-Chun Liu, Juan Chen, Zhi-Feng Zhang, Dan Zhao, Song-Lin Wu, Ren-Zhong Liu, Ze-Fen Wang, Qi Wan
Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain...
May 18, 2018: Cancer Medicine
Junfeng Liu, Qinglei Gao, Tao Xie, Yu Liu, Longjun Luo, Cheng Xu, Lu Shen, Feng Wan, Ting Lei, Fei Ye
Glioblastoma multiforme (GBM) is the most common malignancy in central nervous system. A small subpopulation of GBM cells known as GBM stem-like cells (GSLCs) were supposed to be the most malignant cells among GBM cells as they are resistant to multiple therapies including radiotherapy. In this study, we set up two GSLCs cell lines from the two parental U87 and U251 glioma cell lines, and studied the expression of apoptosis-related genes alteration in GSLCs before and after irradiation. We found that one of the receptors of TNF-related apoptosis-inducing ligand (TRAIL), DR5, was dramatically up-regulated in GSLCs after irradiation (IR)...
May 18, 2018: Clinical and Experimental Medicine
Z-Y Wu, N Wei
OBJECTIVE: Polo like kinase 1 (PLK1), an oncogene, is a ubiquitously expressed serine/threonine protein kinase. We aimed at investigating the role of PLK1 in glioma. PATIENTS AND METHODS: Clinical glioma specimens were obtained from Zhejiang Hospital (Hangzhou, Zhejiang, China). The mRNA and protein levels of PLK1 in glioma tissues and different glioma cells were analyzed by Real-time PCR and Western blot, respectively. The expression of PLK1 protein in glioma tissues was also determined by immunohistochemistry staining...
May 2018: European Review for Medical and Pharmacological Sciences
Xiaoyan He, Mayinur Maimaiti, Yan Jiao, Xuegang Meng, Hongyan Li
Sinomenine, a bioactive alkaloid isolated from the traditional Chinese herb Sinomenium acutum, possesses antiinflammatory, antinociceptive, antifibrotic, and antitumorigenic properties. In this work, we sought to explore the biological effects of sinomenine on glioma cells. It was found that sinomenine caused a concentration-dependent inhibition of viability in both U87 and U251 glioma cells. Sinomenine at 16 μmol/L caused 55% to 60% reduction in the proliferation of U87 and U251 cells. Moreover, sinomenine treatment induced a G0/G1 cell cycle arrest and apoptosis...
January 1, 2018: Technology in Cancer Research & Treatment
Li Li, Yi Yang, Mingxia Wu, Zanyang Yu, Chengqiang Wang, Guojun Dou, Hui He, Hongmei Wang, Na Yang, Hongyi Qi, Xiaoyu Xu
HnRNP A2/B1 has been found to be an oncogenic protein strongly related to the growth of human glioma cells. Herein, β-asarone, the main component in the volatile oil of Acori tatarinowii Rhizoma, inhibited the cell viability, proliferation, and colony formation ability of U251 cells. Moreover, β-asarone induced apoptosis and cell cycle arrest at the G1 phase. Notably, β-asarone suppressed the expression of hnRNP A2/B1 and hnRNPA2/B1 overexpression remarkably reversed β-asarone-mediated apoptosis and cell cycle arrest...
May 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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