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https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#1
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352231/the-direction-of-tumour-growth-in-glioblastoma-patients
#2
Morteza Esmaeili, Anne Line Stensjøen, Erik Magnus Berntsen, Ole Solheim, Ingerid Reinertsen
Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has been an attractive approach in neuro-oncology, suggesting a distinct pattern of lesion spread with a tendency in growing along the white matter (WM) fibre direction for the invasive component. However, the direction of growth is not much studied in vivo. In this study, we sought to study the dominant directions of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two time-points: at radiological diagnosis and as part of the pre-operative planning, both with contrast-enhanced T1-weighted MRIs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29350455/a-novel-prognostic-six-cpg-signature-in-glioblastomas
#3
An-An Yin, Nan Lu, Amandine Etcheverry, Marc Aubry, Jill Barnholtz-Sloan, Lu-Hua Zhang, Jean Mosser, Wei Zhang, Xiang Zhang, Yu-He Liu, Ya-Long He
AIMS: We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). METHODS: A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29349613/tumor-treating-fields-a-new-approach-to-glioblastoma-therapy
#4
REVIEW
Jonathan Rick, Ankush Chandra, Manish K Aghi
Glioblastoma is an aggressive brain malignancy with poor outcomes. Current standard of care involves surgery, radiotherapy and chemotherapy. Even with optimal treatment, 5-year survival rates are low. Many patients are unable to tolerate the considerable side effects that therapy involves and suffer from low quality of life. Anti-mitotic tumor treating fields have shown potential in treating glioblastoma with data suggesting that they prolong disease-free survival and overall survival. Novocure has marketed a device that generates these fields via externally placed electrodes...
January 18, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29349612/dexamethasone-induced-leukocytosis-is-associated-with-poor-survival-in-newly-diagnosed-glioblastoma
#5
Daniel Dubinski, Sae-Yeon Won, Florian Gessler, Johanna Quick-Weller, Bedjan Behmanesh, Simon Bernatz, Marie-Therese Forster, Kea Franz, Karl-Heinz Plate, Volker Seifert, Patrick N Harter, Christian Senft
Despite its well-characterized side effects, dexamethasone is widely used in the pre-, peri- and postoperative neurosurgical setting due to its effective relief of tumor-induced symptoms through the reduction of tumor-associated edema. However, some patients show laboratory-defined dexamethasone induced elevation of white blood cell count, and its impact on glioblastoma progression is unknown. We retrospectively analyzed 113 patients with newly diagnosed glioblastoma to describe the incidence, risk factors and clinical features of dexamethasone-induced leukocytosis in primary glioblastoma patients...
January 18, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29349602/does-the-interval-from-tumour-surgery-to-radiotherapy-influence-survival-in-paediatric-high-grade-glioma
#6
Amedeo A Azizi, Simon Paur, Alexandra Kaider, Karin Dieckmann, Andreas Peyrl, Monika Chocholous, Thomas Czech, Irene Slavc
PURPOSE: Paediatric high grade glioma (pHGG) are rare. Following maximum safe resection, children >3 years with HGG receive radiotherapy as standard of care. Whether the interval from tumour surgery to radiotherapy (ISRT) influences survival is disputed in adults with glioblastoma, data for children are lacking. This retrospective single-centre analysis investigates a possible impact of ISRT on survival in paediatric patients with HGG. METHODS: Survival was analysed in patients aged 3-19 years with non-pontine HGG...
January 18, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#7
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348889/metformin-and-temozolomide-a-synergic-option-to-overcome-resistance-in-glioblastoma-multiforme-models
#8
Silvia Valtorta, Alessia Lo Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348883/spatial-habitats-from-multiparametric-mr-imaging-are-associated-with-signaling-pathway-activities-and-survival-in-glioblastoma
#9
Katherine Dextraze, Abhijoy Saha, Donnie Kim, Shivali Narang, Michael Lehrer, Anita Rao, Saphal Narang, Dinesh Rao, Salmaan Ahmed, Venkatesh Madhugiri, Clifton David Fuller, Michelle M Kim, Sunil Krishnan, Ganesh Rao, Arvind Rao
Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity, impacting response to treatment and overall survival time of 12-15 months. To study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were analyzed to characterize tumor-derived spatial habitats for their relationship with outcome (overall survival) and to identify their molecular correlates (i.e., determine associated tumor signaling pathways correlated with imaging-derived habitat measurements)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348882/microrna203a-suppresses-glioma-tumorigenesis-through-an-atm-dependent-interferon-response-pathway
#10
Chuan He Yang, Yinan Wang, Michelle Sims, Chun Cai, Ping He, Hans Häcker, Junming Yue, Jinjun Cheng, Frederick A Boop, Lawrence M Pfeffer
Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348879/loss-of-neil3-dna-glycosylase-markedly-increases-replication-associated-double-strand-breaks-and-enhances-sensitivity-to-atr-inhibitor-in-glioblastoma-cells
#11
Alex W Klattenhoff, Megha Thakur, Christopher S Chu, Debolina Ray, Samy L Habib, Dawit Kidane
DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B DNA structures. Approximately seven percent of human tumors have an altered NEIL3 gene. However, the role of NEIL3 in replication-associated repair and its impact on modulating treatment response is not known. Here, we report that NEIL3 is localized at the DNA double-strand break (DSB) sites during oxidative DNA damage and replication stress. Loss of NEIL3 significantly increased spontaneous replication-associated DSBs and recruitment of replication protein A (RPA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#12
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348557/sensitizing-tumor-cells-to-conventional-drugs-hsp70-chaperone-inhibitors-their-selection-and-application-in-cancer-models
#13
Vladimir F Lazarev, Dmitry V Sverchinsky, Elena R Mikhaylova, Pavel I Semenyuk, Elena Y Komarova, Sergey A Niskanen, Alina D Nikotina, Anton V Burakov, Viktor G Kartsev, Irina V Guzhova, Boris A Margulis
Hsp70 chaperone controls proteostasis and anti-stress responses in rapidly renewing cancer cells, making it an important target for therapeutic compounds. To date several Hsp70 inhibitors are presented with remarkable anticancer activity, however their clinical application is limited by the high toxicity towards normal cells. This study aimed to develop assays to search for the substances that reduce the chaperone activity of Hsp70 and diminish its protective function in cancer cells. On our mind the resulting compounds alone should be safe and function in combination with drugs widely employed in oncology...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348487/h1-phgfk1-nanoparticles-exert-anti-tumoural-and-radiosensitising-effects-by-inhibition-of-met-in-glioblastoma
#14
Wenyan Zhang, Rui Duan, Jian Zhang, William K C Cheung, Xiaoge Gao, Raymond Zhang, Qing Zhang, Mengxue Wei, Gang Wang, Qian Zhang, Peng-Jin Mei, Hong-Lin Chen, Hsiangfu Kung, Marie C Lin, Zan Shen, Junnian Zheng, Longzhen Zhang, Hong Yao
BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti-angiogenesis mainly impair the prognosis of patients with glioblastoma. The primary and secondary MET aberrant activation is one crucial factor for these resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an angiogenic inhibitor, contains a high-affinity binding domain of MET; however, its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both subcutaneous and orthotopic human glioma cell-xenografted mouse models...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29346317/liposomal-tricurin-a-synergistic-combination-of-curcumin-epicatechin-gallate-and-resveratrol-repolarizes-tumor-associated-microglia-macrophages-and-eliminates-glioblastoma-gbm-and-gbm-stem-cells
#15
Sumit Mukherjee, Juliet N E Baidoo, Samay Sampat, Andrew Mancuso, Lovena David, Leah S Cohen, Shuiqin Zhou, Probal Banerjee
Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin)...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29345288/downregulation-of-mir%C3%A2-205-is-associated-with-glioblastoma-cell-migration-invasion-and-the-epithelial-mesenchymal-transition-by-targeting-zeb1-via-the-akt-mtor-signaling-pathway
#16
Wei Chen, Kuan-Kei Kong, Xin-Ke Xu, Cheng Chen, Hui Li, Fang-Yu Wang, Xiao-Fang Peng, Zhan Zhang, Ping Li, Jun-Liang Li, Fang-Cheng Li
Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of recent advancements in surgical techniques, chemotherapy, and radiation therapy, patients with GBM often face a dire prognosis. MicroRNAs have been shown to modulate the aggressiveness of various cancers, and have emerged as possible therapeutic agents for the management of GBM. miR‑205 is dysregulated in glioma and act as a prognostic indicator. However, the role of miR‑205 in the development of GBM has not been elucidated...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345190/magnetoelectric-nanoparticles-for-delivery-of-antitumor-peptides-into-glioblastoma-cells-by-magnetic-fields
#17
Tiffanie S Stewart, Abhignyan Nagesetti, Rakesh Guduru, Ping Liang, Emmanuel Stimphil, Ali Hadjikhani, Luis Salgueiro, Jeffrey Horstmyer, Renzhi Cai, Andrew Schally, Sakhrat Khizroev
AIM: We studied externally controlled anticancer effects of binding tumor growth inhibiting synthetic peptides to magnetoelectric nanoparticles (MENs) on treatment of glioblastomas. METHODS: Hydrothermally synthesized 30-nm MENs had the core-shell composition of CoFe2O4@BaTiO3. Molecules of growth hormone-releasing hormone antagonist of the MIA class (MIA690) were chemically bound to MENs. In vitro experiments utilized human glioblastoma cells (U-87MG) and human brain microvascular endothelial cells...
January 18, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29344889/quantitative-analysis-of-tyrosine-kinase-signaling-across-differentially-embedded-human-glioblastoma-tumors
#18
Hannah Johnson, Forest M White
Glioblastoma is the most aggressive primary brain tumor with a poor mean survival even with the current standard of care. Kinase signaling analyses of clinical glioblastoma samples provide a physiologically relevant view of oncogenic signaling networks. Here, we describe the methods that enable the quantification of protein expression profiles and phosphotyrosine signaling across flash frozen and optimal cutting temperature (OCT) compound embedded tumor specimens. The data derived from these experiments can be used to identify the intra- and inter-patient heterogeneity present in these tumors...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344278/potent-peptide-conjugated-silicon-phthalocyanines-for-tumor-photodynamic-therapy
#19
Qian Liu, Mingpei Pang, Sihai Tan, Jin Wang, Qingle Chen, Kai Wang, Wenjie Wu, Zhangyong Hong
Phthalocyanines (Pcs) are a group of promising photosensitizers for use in photodynamic therapy (PDT). However, their extremely low solubility and their strong tendency to aggregate in aqueous solution greatly restrict their application. Conjugation of Pc macrocycles with peptide ligands could be a very useful strategy to optimize the physical properties of Pcs not only by increasing their water solubility and reducing their aggregation but also by endowing the conjugates with a tumor-targeting capability. To develop highly potent photosensitizers for tumor PDT, we prepared new peptide-conjugated photosensitizers using silicon Pc (SiPc), which has much higher photodynamic activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or simply cRGD) as the peptide moiety...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344264/preclinical-and-clinical-implications-of-tert-promoter-mutation-in-glioblastoma-multiforme
#20
Da Eun Jeong, Seon Rang Woo, Hyun Nam, Do-Hyun Nam, Jae-Ho Lee, Kyeung Min Joo
The promoter region of the telomerase reverse transcriptase gene (TERT) is mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the present study, preclinical and clinical implications of the mutation were analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations between the TERT promoter mutation and a number of preclinical/clinical characteristics were analyzed. Notably, the TERT promoter mutation was identified in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation capacity; while the TERT promoter mutation was identified in 33...
December 2017: Oncology Letters
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