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O H Minchenko, I A Garmash, D O Minchenko, A Y Kuznetsova, O O Ratushna
We have studied the effect of hypoxia on the expression level of mRNA of the basic enzymes of pentose-phosphate cycle (G6PD, TKT, TALDO1, PGLS and RPIA) and glucose-6-phosphate isomerase (GPI) in U87 glioma cells in relation to inhibition of IRE1 (inositol requiring enzyme 1). It was shown that hypoxia leads to up-regulation of the expression of GPI and PGLS genes and to down-regulation of TALDO1 and RPIA genes in control glioma cells. Changes for GPI gene were more significant than for other genes. At the same time, inhibition of IRE1 modified the effect of hypoxia on the expression of all studied genes...
January 2017: Ukrainian Biochemical Journal
Florien W Boele, Martin Klein, Irma M Verdonck-de Leeuw, Pim Cuijpers, Jan J Heimans, Tom J Snijders, Maaike Vos, Ingeborg Bosma, Cees C Tijssen, Jaap C Reijneveld
Depressive symptoms are common in glioma patients, and can negatively affect health-related quality of life (HRQOL). We performed a nation-wide randomized controlled trial to evaluate the effects of an online guided self-help intervention for depressive symptoms in adult glioma patients. Glioma patients with depressive symptoms were randomized to a 5-week online course based on problem-solving therapy, or a waiting list control group. After having received the intervention, the glioma patient groups combined were compared with patients with cancer outside the central nervous system (non-CNS cancer controls), who also received the intervention...
December 13, 2017: Journal of Neuro-oncology
Fernando Carceller, Francisco Bautista, Irene Jiménez, Raquel Hladun-Álvaro, Cécile Giraud, Luca Bergamaschi, Madhumita Dandapani, Isabelle Aerts, François Doz, Didier Frappaz, Michela Casanova, Bruce Morland, Darren R Hargrave, Gilles Vassal, Andrew D J Pearson, Birgit Geoerger, Lucas Moreno, Lynley V Marshall
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses...
December 13, 2017: Journal of Neuro-oncology
Wenyin Shi, Erik S Blomain, Joshua Siglin, Joshua J Palmer, Tu Dan, Yang Wang, Maria Werner-Wasik, Jon Glass, Lyndon Kim, Voichita Bar Ad, Deepak Bhamidipati, James J Evans, Kevin Judy, Christopher J Farrell, David W Andrews
Bevacizumab failure is a major clinical problem in the management of high grade gliomas (HGG), with a median overall survival (OS) of < 4 months. This study evaluated the feasibility and efficacy of fractionated stereotactic re-irradiation (FSRT) for patients progressed after Bevacizumab treatment. Retrospective review was conducted of 36 patients treated with FSRT after progression on bevacizumab. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints...
December 12, 2017: Journal of Neuro-oncology
Joseph R Linzey, Bernard L Marini, Amy Pasternak, Cory Smith, Zac Miklja, Lili Zhao, Chandan Kumar-Sinha, Alyssa Paul, Nicholas Harris, Patricia L Robertson, Lindsey M Hoffman, Arul Chinnaiyan, Rajen Mody, Carl Koschmann
The number of targeted therapies utilized in precision medicine are rapidly increasing. Neuro-oncology offers a unique challenge due to the varying blood brain barrier (BBB) penetration of each agent. Neuro-oncologists face a difficult task weighing the growing number of potential targeted therapies and their likelihood of BBB penetration. We developed the CNS TAP Working Group and performed an extensive literature review for the evidence-based creation of the CNS TAP tool, which was retrospectively validated by analyzing brain tumor patients who underwent therapy targeted based on genomic results from an academic sequencing study (MiOncoseq, n = 17) or private molecular profiling (Foundation One, n = 7)...
December 12, 2017: Journal of Neuro-oncology
Barbara Banelli, Alessandra Forlani, Giorgio Allemanni, Anna Morabito, Maria Pia Pistillo, Massimo Romani
Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode...
2017: International Journal of Genomics
Xiao Gao, Xing Guo, Hao Xue, Wei Qiu, Xiaofan Guo, Jinsen Zhang, Mingyu Qian, Tong Li, Qinglin Liu, Jie Shen, Lin Deng, Gang Li
Long noncoding RNAs (lncRNAs) have been shown to play critical roles in cancer. lncTCF7 (gene symbol: WSPAR) has been reported to maintain stemness in hepatocellular carcinoma (HCC) stem cells. However, little is known about the role of lncTCF7 in glioma. The aim of this study was to identify the role of lncTCF7 in the pathogenesis of glioma. We analysed the relationship of lncTCF7 expression with clinicopathological characteristics in glioma patients. Our results showed that lncTCF7 expression was increased in glioma tissues compared with that in normal brain tissues (P < 0...
December 12, 2017: Scientific Reports
Tong Zhang, Daofei Ji, Peng Wang, Liang Dong, Lei Jin, Hengliang Shi, Xuejiao Liu, Qingming Meng, Rutong Yu, Shangfeng Gao
The RIO (right open reading frame) protein kinases include RIOK1, RIOK2 and RIOK3. Emerging evidence has suggested an important role of RIO kinases in cancer cell proliferation, apoptosis, migration and invasion. However, the expression profile and specific roles of RIOK3 are largely unknown during glioma progression. In the current study, quantitative real-time PCR, Western blot, and immunohistochemical analysis showed that RIOK3 was upregulated in glioma tissues. Available database analysis revealed that higher levels of RIOK3 were associated with poorer survival outcome in glioma patients...
December 9, 2017: Cancer Letters
Cornelis M van Tilburg, Florian Selt, Felix Sahm, Heidi Bächli, Stefan M Pfister, Olaf Witt, Till Milde
Infants with low-grade glioma (LGG) and diencephalic syndrome have a poor outcome. The patient described here had a desmoplastic infantile astrocytoma harboring a BRAF V600E mutation. After relapse following initial standard chemotherapy treatment, he was successfully treated with the BRAF V600E inhibitor vemurafenib at the age of 3 years 11 months and 5 years 0 months. A rapid response was observed on both occasions. This illustrates the possibility of continuous oncogenic addiction and the therapeutic potential of BRAF V600E inhibitor monotherapy in LGG, even in very young severely compromised children...
December 12, 2017: Pediatric Blood & Cancer
Kai Wang, Yinyan Wang, Xing Fan, Yanong Li, Xing Liu, Jiangfei Wang, Lin Ai, Jianping Dai, Tao Jiang
In this study we aimed to identify the anatomic features of 1p/19q co-deletion and investigate the predictive values of tumor location and radiological characteristics for the survival of anaplastic oligodendroglial (AO) glioma patients. Voxel-based lesion-symptom mapping (VLSM) analysis was applied to define the brain regions associated with occurrence of 1p/19q co-deletion in a cohort of 206 AO tumor patients (discovery set) treated between May 2009 and September 2013. Retrospectively, the acquired clusters and radiological features were subjected to Kaplan-Meier survival analysis using data from the Chinese Glioma Genome Atlas (validation set) to evaluate their prognostic role in AO patients...
December 11, 2017: Journal of Neuro-oncology
Barbara Oldrini, Wan-Ying Hsieh, Hediye Erdjument-Bromage, Paolo Codega, Maria Stella Carro, Alvaro Curiel-García, Carl Campos, Maryam Pourmaleki, Christian Grommes, Igor Vivanco, Daniel Rohle, Craig M Bielski, Barry S Taylor, Travis J Hollmann, Marc Rosenblum, Paul Tempst, John Blenis, Massimo Squatrito, Ingo K Mellinghoff
Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin β family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output...
December 11, 2017: Nature Communications
Jing Zhang, Yanlin Song, Min He, Qingqing Ren, Yunhui Zeng, Zhiyong Liu, Hao Liu, Jianguo Xu
OBJECT: The aim of this study was to systematically evaluate the diagnostic performance of increased signal intensity within the resection cavity on fluid-attenuated inversion recovery (FLAIR) sequences for detection of progression in patients with glioma through performing a meta-analysis. METHODS: PubMed, Web of Science, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for potentially relevant literature. The study characteristics and relevant data were extracted...
December 8, 2017: World Neurosurgery
Lan Zheng, Huanyin Li, Yanqing Mo, Gong Qi, Bin Liu, Jing Zhao
PI3K-AKT-mTOR signaling is a valuable treatment target for human glioma. LY3023414 is a novel, highly-potent and pan PI3K-AKT-mTOR inhibitor. Here, we show that LY3023414 efficiently inhibited survival and proliferation of primary and established human glioma cells. Meanwhile, apoptosis activation was observed in LY3023414-treated glioma cells. LY3023414 blocked AKT-mTOR activation in human glioma cells. Further studies show that LY3023414 induced feedback activation of autophagy in U251MG cells. On the other hand, autophagy inhibition via adding pharmacological inhibitors or silencing Beclin-1/ATG-5 significantly potentiated LY3023414-induced glioma cell apoptosis...
November 17, 2017: Oncotarget
Tianfu Yu, Yingyi Wang, Qi Hu, WeiNing Wu, Youzhi Wu, Wenjin Wei, Dongfeng Han, Yongping You, Ning Lin, Ning Liu
Enhancer of zeste homolog 2 (EZH2) is the catalytic unit of polycomb repressive complex 2 (PRC2) which epigenetically silences many genes involved in tumor-suppressive mechanisms via the trimethylation of lysine 27 of histone H3 (H3K27me3). We recently found that overexpression of EZH2 was associated with poor outcome of glioblastoma (GBM). In this study, we examined the antitumor effects of the EZH2 inhibitor GSK343 on glioma cells in vitro and in vivo. The proliferation and cell cycle of glioma cells was measured...
November 17, 2017: Oncotarget
Ying-Chun Song, Gai-Xia Lu, Hong-Wei Zhang, Xiao-Ming Zhong, Xian-Ling Cong, Shao-Bo Xue, Rui Kong, Dan Li, Zheng-Yan Chang, Xiao-Feng Wang, Yun-Jie Zhang, Ran Sun, Li Chai, Ru-Ting Xie, Ming-Xiang Cai, Ming Sun, Wei-Qing Mao, Hui-Qiong Yang, Yun-Chao Shao, Su-Yun Fan, Ting-Miao Wu, Qing Xia, Zhong-Wei Lv, David A Fu, Yu-Shui Ma
Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples...
November 14, 2017: Oncotarget
Yuji Piao, Verlene Henry, Ningyi Tiao, Soon Young Park, Juan Martinez-Ledesma, Jian Wen Dong, Veerakumar Balasubramaniyan, John F de Groot
Intercellular cell adhesion molecule 1 (ICAM-1; also known as CD54) is overexpressed in bevacizumab-resistant glioblastoma. In the present study, we tested our hypothesis that highly expressed ICAM-1 mediates glioblastoma's resistance to antiangiogenic therapy. We validated ICAM-1 overexpression in tumors resistant to antiangiogenic therapy using real-time polymerase chain reaction, immunohistochemistry, and Western blotting. We also detected ICAM1 expression in most glioma stem cells (GSCs). We investigated the mechanism of ICAM-1 overexpression after bevacizumab treatment and found that ICAM-1 protein expression was markedly increased in a time-dependent manner in GSC11 and GSC17 cells under hypoxic conditions in vitro...
November 14, 2017: Oncotarget
G-B Wang, J-H Liu, J Hu, K Xue
OBJECTIVE: Gliomas are accompanied with high mortality owning to their invasive peculiarity and vulnerability to drug resistance. miR-21 is a vital oncogenic miRNA that regulates drug resistance of tumor cells. This study aims to elucidate the function of miR-21 in human glioma cells resistant to carmustine (BCNU) and to demonstrate the underlying molecular mechanism. MATERIALS AND METHODS: BCNU-sensitive cells (SWOZ2 cells) were transfected with miR-21 agomir and negative control, and BCNU-resistance cells (SWOZ2-BCNU cells) were transfected with miR-21 antagomir and negative control...
November 2017: European Review for Medical and Pharmacological Sciences
Z-S Yuan, Y Cao, Z-Y Li
OBJECTIVE: Gliomas are accompanied with high mortality owning to their invasive peculiarity and vulnerability to drug resistance. miR-21 is a vital oncogenic miRNA that regulates drug resistance of tumor cells. This study aims to elucidate the function of miR-21 in human glioma cells resistant to carmustine (BCNU) and to demonstrate the underlying molecular mechanism. MATERIALS AND METHODS: BCNU-sensitive cells (SWOZ2 cells) were transfected with miR-21 agomir and negative control, and BCNU-resistance cells (SWOZ2-BCNU cells) were transfected with miR-21 antagomir and negative control...
November 2017: European Review for Medical and Pharmacological Sciences
Varidh Katiyar, Ravi Sharma, Hitesh Kumar Gurjar
No abstract text is available yet for this article.
December 4, 2017: Operative Neurosurgery (Hagerstown, Md.)
Tamara Ius, Yari Ciani, Maria Elisabetta Ruaro, Miriam Isola, Marisa Sorrentino, Michela Bulfoni, Veronica Candotti, Cecilia Correcig, Evgenia Bourkoula, Ivana Manini, Enrico Pegolo, Damiano Mangoni, Stefania Marzinotto, Slobodanka Radovic, Barbara Toffoletto, Federica Caponnetto, Andrea Zanello, Laura Mariuzzi, Carla Di Loreto, Antonio Paolo Beltrami, Silvano Piazza, Miran Skrap, Daniela Cesselli
Background: While recent genome wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived stem cells representative of the glioma microenvironment. Methods: By next generation sequencing, we analyzed the transcriptional profile of GASC derived from patients that underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery...
December 7, 2017: Neuro-oncology
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