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High grade glioma

Ashley M Stokes, Charles P Hart, C Chad Quarles
High-grade gliomas are often characterized by hypoxia, which is associated with both poor long-term prognosis and therapy resistance. The adverse role hypoxia plays in treatment resistance and disease progression has led to the development of hypoxia imaging methods and hypoxia-targeted treatments. Here, we determined the tumor hypoxia and vascular perfusion characteristics of 2 rat orthotopic glioma models using 18-fluoromisonidozole positron emission tomography. In addition, we determined tumor response to the hypoxia-activated prodrug evofosfamide (TH-302) in these rat glioma models...
September 2016: Tomography: a Journal for Imaging Research
Pedro Roldán, Sergio García, Josep González, Luis Alberto Reyes, Jorge Torales, Ricard Valero, Laura Oleaga, Joaquim Enseñat
OBJECTIVES: Intra-operative magnetic resonance imaging (iMRI) is a recently introduced tool in the most advanced neurosurgical operating rooms worldwide. We present our preliminary experience in brain tumour surgery with low field PoleStar N30® intraoperative MRI since its introduction in 2013 in the Barcelona Clinic Hospital. MATERIAL AND METHODS: A prospective non-randomised study was conducted on cases operated on using iMRI and intention of complete removal up to October 2015...
October 14, 2016: Neurocirugía
Zhijie Dai, Jun Wu, Fenghua Chen, Quan Cheng, Mingyu Zhang, Ying Wang, Yong Guo, Tao Song
CXCL5 and its receptor CXCR2 have been found to be involved in tumorigenesis and cancer progression. Recent studies have shown that CXCR2 is upregulated in glioma tissues, and associated with poor prognosis and recurrence. However, the role of CXCL5/CXCR2 signaling in mediating the malignant phenotypes of glioma cells, as well as the underlying mechanism, still remains unclear. In the present study, we found that CXCL5 was upregulated in glioma tissues compared to that noted in normal brain tissues. High CXCL5 levels were significantly associated with higher tumor grade, advanced clinical stage, and shorter survival time of glioma patients...
October 10, 2016: Oncology Reports
Ai-Shun Guo, Yi-Qun Huang, Xu-Dong Ma, Rui-Sheng Lin
The present study aimed to investigate the differential expression and clinical significance of histone methyltransferase G9a, histone H3K9me2 and histone H3K9me1 in human brain glioma and adjacent tissue samples. It also aimed to observe the effect and mechanism of BIX‑01294, as an inhibitor of methyltransferase G9a, on the proliferation, apoptosis, methylation of H3K9 and H3K27, and the acetylation in U251 glioma cells in vitro. The differential expression of methyltransferase G9a, histone H3K9me2 and histone H3K9me1 in in human brain glioma and adjacent tissues were analyzed by immunohistochemistry, a growth curve of U251 cells following treatment with BIX‑01294 was determined using the MTT assay...
October 6, 2016: Molecular Medicine Reports
Divine E Ediebah, Jaap C Reijneveld, Martin J B Taphoorn, Corneel Coens, Efstathios Zikos, Neil K Aaronson, Jan J Heimans, Andrew Bottomley, Martin Klein
PURPOSE: Clinical trials in glioma patients with neurocognitive deficits face challenges due to lacking or unreliable patient self-reports on their health-related quality of life (HRQOL). Patient-proxy data could help solve this issue. We determined whether patient-proxy concordance levels were affected by patients' neurocognitive functioning. METHODS: Patient and patient-by-proxy HRQOL ratings were assessed via SF-36 and EORTC QLQ-BN20, respectively, in 246 patients...
October 15, 2016: Quality of Life Research
Raymond Y Huang, Patrick Y Wen
The Response Assessment in Neuro-Oncology (RANO) Working Group is an international multidisciplinary group whose goal is to improve response criteria and define endpoints for neuro-oncology trials. The RANO criteria for high-grade gliomas attempt to address the issues of pseudoprogression, pseudoresponse, and nonenhancing tumor progression. Incorporation of advanced MR imaging may eventually help improve the ability of these criteria to define enhancing and nonenhancing disease better. The RANO group has also developed criteria for neurologic response and evaluation of patients receiving immunologic therapies...
November 2016: Magnetic Resonance Imaging Clinics of North America
Alicia Martı Nez-González, Gabriel F Calvo, Jose M Ayuso, Ignacio Ochoa, Luis J Fernández, Víctor M Pérez-García
This chapter explores the use of mathematical models as promising and powerful tools to understand the complexity of tumors and their, frequently, hypoxic environment. We focus on gliomas, which are primary brain tumors derived from glial cells, mainly astrocytes and/or oligodendrocytes. A variety of mathematical models, based on ordinary and/or partial differential equations, have been developed both at the micro and macroscopic levels. The aim here is to describe in a quantitative way key physiopathological mechanisms relevant in these types of malignancies and to suggest optimal therapeutical strategies...
2016: Advances in Experimental Medicine and Biology
Chuanbao Zhang, Jiye Li, Haoyuan Wang, Sonya Wei Song
High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences...
October 12, 2016: Oncotarget
Xuejiao Liu, Yulong Chong, Yiming Tu, Ning Liu, Chenglong Yue, Zhenglei Qi, Huize Liu, Yao Yao, Hongmei Liu, Shangfeng Gao, Mingshan Niu, Rutong Yu
BACKGROUND: Malignant gliomas are associated with a high mortality rate, and effective treatment options are limited. Thus, the development of novel targeted treatments to battle this deadly disease is imperative. METHODS: In this study, we investigated the in vitro effects of the novel reversible chromosomal region maintenance 1 (CRM1) inhibitor S109 on cell proliferation in human gliomas. S109 was also evaluated in an intracranial glioblastoma xenograft model...
October 12, 2016: Journal of Hematology & Oncology
Fei-Yi-Fan Wang, Chun-Sheng Kang, Si-Yi Wang-Gou, Chun-Hai Huang, Cheng-Yuan Feng, Xue-Jun Li
Epidermal Growth Factor like domain 7 (EGFL7), also known as Vascular Endothelial-statin (VE-statin), is a secreted angiogenic factor. Recent data have demonstrated the potential oncogenic role and prognostic significance of EGFL7 in several human cancers. However, the clinical signature and further mechanisms of EGFL7's function in gliomagenesis are poorly understood. In the present study, we found that increased EGFL7 expression was associated with tumor grade. High expression of EGFL7 in EGFRvIII-positive glioblastoma multiforme (GBM) was determined to be a strong and independent risk factor for reduced life expectancy...
October 7, 2016: Cancer Letters
Robert J Harris, Timothy F Cloughesy, Linda M Liau, Phioanh L Nghiemphu, Albert Lai, Whitney B Pope, Benjamin M Ellingson
Acidity within the extracellular milieu is a hallmark of cancer. There is a current need for fast, high spatial resolution pH imaging techniques for clinical evaluation of cancers, including gliomas. Chemical exchange saturation transfer (CEST) MRI targeting fast-exchanging amine protons can be used to obtain high-resolution pH-weighted images, but conventional CEST acquisition strategies are slow. There is also a need for more accurate MR simulations to better understand the effects of amine CEST pulse sequence parameters on pH-weighted image contrast...
September 15, 2016: NMR in Biomedicine
Veronica Villani, Roberta Merola, Antonello Vidiri, Alessandra Fabi, Mariantonia Carosi, Diana Giannarelli, Laura Marucci, Marta Maschio, Carmine M Carapella, Andrea Pace
PURPOSE: To explore the efficacy and toxicity of an extended schedule of temozolomide (50 mg/mq 1 week on/1 week off) in a population of newly diagnosed low-grade gliomas (LGG). METHODS: Primary endpoints were progression-free survival (PFS) at 12 and 24 months and response rate evaluated with Response Assessment in Neuro-Oncology Criteria. Secondary endpoints were clinical benefit (reduction of seizures frequency), reduction of steroid, and modifications of Karnofsky Performance Status...
September 22, 2016: Tumori
Manabu Kinoshita, Mio Sakai, Hideyuki Arita, Tomoko Shofuda, Yasuyoshi Chiba, Naoki Kagawa, Yoshiyuki Watanabe, Naoya Hashimoto, Yasunori Fujimoto, Toshiki Yoshimine, Katsuyuki Nakanishi, Yonehiro Kanemura
Reports have suggested that tumor textures presented on T2-weighted images correlate with the genetic status of glioma. Therefore, development of an image analyzing framework that is capable of objective and high throughput image texture analysis for large scale image data collection is needed. The current study aimed to address the development of such a framework by introducing two novel parameters for image textures on T2-weighted images, i.e., Shannon entropy and Prewitt filtering. Twenty-two WHO grade 2 and 28 grade 3 glioma patients were collected whose pre-surgical MRI and IDH1 mutation status were available...
2016: PloS One
Oliver Oehlke, Michael Mix, Erika Graf, Tanja Schimek-Jasch, Ursula Nestle, Irina Götz, Sabine Schneider-Fuchs, Astrid Weyerbrock, Irina Mader, Brigitta G Baumert, Susan C Short, Philipp T Meyer, Wolfgang A Weber, Anca-Ligia Grosu
BACKGROUND: The higher specificity of amino-acid positron emission tomography (AA-PET) in the diagnosis of gliomas, as well as in the differentiation between recurrence and treatment-related alterations, in comparison to contrast enhancement in T1-weighted MRI was demonstrated in many studies and is the rationale for their implementation into radiation oncology treatment planning. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI concerning the definition of the gross tumor volume (GTV)...
October 5, 2016: BMC Cancer
Jinquan Cai, Chuanbao Zhang, Wei Zhang, Guangzhi Wang, Kun Yao, Zhiliang Wang, Guanzhang Li, Zenghui Qian, Yongli Li, Tao Jiang, Chuanlu Jiang
Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. Malignant astrocytic tumors such as glioblastoma (GBM) are the most lethal intracranial tumors. However, the clinical practicability and significance of molecular parameters for the diagnostic and prognostic prediction of astrocytic tumors is still limited. In this study, we detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and observed the association of IDH1-R132H with ATRX and Ki-67 expression...
2016: Oncoscience
Tong Ren, Shide Lin, Zhongfeng Wang, Aijia Shang
Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I-IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography-tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification...
2016: OncoTargets and Therapy
Bo Ram Kang, Seung-Hoon Yang, Bo-Ryehn Chung, Woong Kim, YoungSoo Kim
High-grade glioma is a highly malignant and metastatic brain cancer, resistant to many existing anticancer treatments. In such glioma cancer cells, the glucose-regulated protein 78 kDa (GRP78) is particularly highly up-regulated. Former studies have thus targeted mutation-free GRP78 not only to detect glioma cancer cells specifically but also to enhance cytotoxic effect. We focus on cell surface-expressed GRP78 as a target for suppressing high-grade glioma cell lines. Glioblastoma multiforme (GBM) cell line, highly malignant glioma cells, was first injected into 5-week-old athymic mice to confirm and compare GRP78 expression in vivo in xenografted and normal brain tissue...
October 7, 2016: Scientific Reports
Yunwei Ou, Zitong Zhao, Weimin Zhang, Qingnan Wu, Chuanyue Wu, Xuefeng Liu, Ming Fu, Nan Ji, Dan Wang, Jiaji Qiu, Liwei Zhang, Chunjiang Yu, Yongmei Song, Qimin Zhan
Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue samples. High Kindlin-2 expression was correlated with high pathological grade and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1 (YB-1) and β-catenin expression, Kindlin-2 formed a transcriptional complex with YB-1 and β-catenin that bound to the EGFR promoter and enhanced transcription...
October 4, 2016: Oncotarget
Stefan Grossauer, Katharina Koeck, Nicole E Murphy, Ian D Meyers, Mathieu Daynac, Nathalene Truffaux, Albert Y Truong, Theodore P Nicolaides, Martin McMahon, Mitchel S Berger, Joanna J Phillips, C David James, Claudia K Petritsch
Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition...
October 3, 2016: Oncotarget
S A Cherepanov, K I Cherepanova, N F Grinenko, O M Antonova, V P Chekhonin
We studied the effect of an activator (ShTh) and an inhibitor (cyclopamine) of the Hedgehog signaling pathway on proliferation of human glioma cell lines U87-MG and U251-MG and cultured human astrocytes. The Hedgehog signaling pathway is activated in glioma cells, but not in cultured human astrocytes. Experiments with Shh and cyclopamine can serve as an additional criterion for assessing activity of Hedgehog signaling in known cell lines and primary cultured cells.
September 2016: Bulletin of Experimental Biology and Medicine
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