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notch signaling in glioma

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https://www.readbyqxmd.com/read/27858266/reverse-phase-protein-arrays-enable-glioblastoma-molecular-subtyping
#1
Gregor Hutter, Martin Sailer, Tej Deepak Azad, André O von Bueren, Peter Nollau, Stephan Frank, Cristobal Tostado, Durga Sarvepalli, Arkasubhra Ghosh, Marie-Françoise Ritz, Jean-Louis Boulay, Luigi Mariani
In the present study we investigated the phosphorylation status of the 12 most important signaling cascades in glioblastomas. More than 60 tumor and control biopsies from tumor center and periphery (based on neuronavigation) were subjected to selective protein expression analysis using reverse-phase protein arrays (RPPA) incubated with antibodies against posttranslationally modified cancer pathway proteins. The ratio between phosphorylated (or modified) and non-phosphorylated protein was assessed. All samples were histopathologically validated and proteomic profiles correlated with clinical and survival data...
November 17, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27826680/phase-i-study-of-ro4929097-with-bevacizumab-in-patients-with-recurrent-malignant-glioma
#2
Edward Pan, Jeffrey G Supko, Thomas J Kaley, Nicholas A Butowski, Timothy Cloughesy, Jinkyu Jung, Serena Desideri, Stuart Grossman, Xiaobu Ye, Deric M Park
Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combination of bevacizumab and RO4929097, an inhibitor of the notch signaling cascade. A phase I clinical trial was conducted through the Adult Brain Tumor Consortium in subjects with recurrent malignant glioma...
November 8, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27801803/mir-92a-3p-exerts-various-effects-in-glioma-and-glioma-stem-like-cells-specifically-targeting-cdh1-%C3%AE-catenin-and-notch-1-akt-signaling-pathways
#3
Hang Song, Yao Zhang, Na Liu, Sheng Zhao, Yan Kong, Liudi Yuan
MicroRNAs (miRNAs) are implicated in the regulation of tumor progression and stemness of cancer stem-like cells. Recently, miR-92a-3p was reported to be up-regulated in human glioma samples. Nevertheless, the precise role of miR-92a-3p in glioma cells and glioma stem-like cells (GSCs) has not been fully elucidated. It is necessary to clarify the function of miR-92a-3p in glioma and GSCs to develop novel therapeutic approaches for glioma patients. In the present study, we applied methyl-thiazolyl-tetrazolium (MTT) assay and Transwell assay to measure the proliferation rate and metastatic potential of glioma cells...
October 27, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27713911/weaponizing-human-egf-containing-fibulin-like-extracellular-matrix-protein-1-efemp1-for-21-st-century-cancer-therapeutics
#4
Yi-Hong Zhou, Yuanjie Hu, Liping Yu, Chao Ke, Christopher Vo, Hao Hsu, Zhenzhi Li, Anne T Di Donato, Abhishek Chaturbedi, Ji Won Hwang, Eric R Siegel, Mark E Linskey
De-regulated EFEMP1 gene expression in solid tumors has been widely reported with conflicting roles. We dissected EFEMP1 to identify domains responsible for its cell context-dependent dual functions, with the goal being to construct an EFEMP1-derived tumor-suppressor protein (ETSP) that lacked tumor-promoting function. Exon/intron boundaries of EFEMP1 were used as boundaries of functional modules in constructing EFEMP1 variants, with removal of various module(s), and/or mutating an amino acid residue to convert a weak integrin binding-site into a strong one...
2016: Oncoscience
https://www.readbyqxmd.com/read/27183910/notch-blockade-combined-with-radiation-therapy-and-temozolomide-prolongs-survival-of-orthotopic-glioblastoma
#5
Sanaz Yahyanejad, Henry King, Venus Sosa Iglesias, Patrick V Granton, Lydie M O Barbeau, Stefan J van Hoof, Arjan J Groot, Roger Habets, Jos Prickaerts, Anthony J Chalmers, Daniëlle B P Eekers, Jan Theys, Susan C Short, Frank Verhaegen, Marc Vooijs
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation resistance and intrinsic or acquired TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC). The NOTCH signaling pathway is expressed and active in human glioblastoma and NOTCH inhibitors attenuate tumor growth in vivo in xenograft models. Here we show using an image guided micro-CT and precision radiotherapy platform that a combination of the clinically approved NOTCH/γ-secretase inhibitor (GSI) RO4929097 with standard of care (TMZ + RT) reduces tumor growth and prolongs survival compared to dual combinations...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27154916/molecular-and-clinical-effects-of-notch-inhibition-in-glioma-patients-a-phase-0-i-trial
#6
Ran Xu, Fumiko Shimizu, Koos Hovinga, Kathryn Beal, Sasan Karimi, Leif Droms, Kyung K Peck, Philip Gutin, J Bryan Iorgulescu, Thomas Kaley, Lisa DeAngelis, Elena Pentsova, Craig Nolan, Christian Grommes, Timothy Chan, Dylan Bobrow, Adilia Hormigo, Justin R Cross, Nian Wu, Naoko Takebe, Katherine Panageas, Percy Ivy, Jeffrey G Supko, Viviane Tabar, Antonio Omuro
PURPOSE: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role. EXPERIMENTAL DESIGN: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters...
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26977157/glioma-stem-cells-and-their-microenvironments-providers-of-challenging-therapeutic-targets
#7
REVIEW
Elena Codrici, Ana-Maria Enciu, Ionela-Daniela Popescu, Simona Mihai, Cristiana Tanase
Malignant gliomas are aggressive brain tumors with limited therapeutic options, possibly because of highly tumorigenic subpopulations of glioma stem cells. These cells require specific microenvironments to maintain their "stemness," described as perivascular and hypoxic niches. Each of those niches induces particular signatures in glioma stem cells (e.g., activation of Notch signaling, secretion of VEGF, bFGF, SDF1 for the vascular niche, activation of HIF2α, and metabolic reprogramming for hypoxic niche)...
2016: Stem Cells International
https://www.readbyqxmd.com/read/26967788/bioinformatic-analyses-reveal-a-distinct-notch-activation-induced-by-stat3-phosphorylation-in-the-mesenchymal-subtype-of-glioblastoma
#8
Wen Cheng, Chuanbao Zhang, Xiufang Ren, Yang Jiang, Sheng Han, Yang Liu, Jinquan Cai, Mingyang Li, Kuanyu Wang, Yanwei Liu, Huimin Hu, Qingbin Li, Pei Yang, Zhaoshi Bao, Anhua Wu
OBJECTIVE Glioblastoma (GBM) is the most common and lethal type of malignant glioma. The Cancer Genome Atlas divides the gene expression-based classification of GBM into classical, mesenchymal, neural, and proneural subtypes, which is important for understanding GBM etiology and for designing effective personalized therapy. Signal transducer and activator of transcription 3 (STAT3), a critical transcriptional activator in tumorigenesis, is persistently phosphorylated and associated with an unfavorable prognosis in GBM...
March 11, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/26943907/the-curcumin-analog-c-150-influencing-nf-%C3%AE%C2%BAb-upr-and-akt-notch-pathways-has-potent-anticancer-activity-in-vitro-and-in-vivo
#9
László Hackler, Béla Ózsvári, Márió Gyuris, Péter Sipos, Gabriella Fábián, Eszter Molnár, Annamária Marton, Nóra Faragó, József Mihály, Lajos István Nagy, Tibor Szénási, Andrea Diron, Árpád Párducz, Iván Kanizsai, László G Puskás
C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model...
2016: PloS One
https://www.readbyqxmd.com/read/26893479/drosophila-brat-and-human-ortholog-trim3-maintain-stem-cell-equilibrium-and-suppress-brain-tumorigenesis-by-attenuating-notch-nuclear-transport
#10
Subhas Mukherjee, Carol Tucker-Burden, Changming Zhang, Kenneth Moberg, Renee Read, Costas Hadjipanayis, Daniel J Brat
Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth...
April 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/26828272/gamma-glutamylcyclotransferase-promotes-the-growth-of-human-glioma-cells-by-activating-notch-akt-signaling
#11
Shang-Hang Shen, Ning Yu, Xi-Yao Liu, Guo-Wei Tan, Zhan-Xiang Wang
Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects...
March 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26768745/alpinetin-targets-glioma-stem-cells-by-suppressing-notch-pathway
#12
Jianpeng Wang, Zhiyong Yan, Xia Liu, Shusheng Che, Chao Wang, Weicheng Yao
Glioma is among the most common human malignancies with poor prognosis. Glioma stem cells (GSCs) are the culprit of glioma, suggesting that GSCs are potential therapeutic targets. Notch signaling pathway plays a pivotal role for the function of GSCs, implying that suppression of Notch pathway may be an effective strategy for GSC-targeting therapy. In this study, we found that alpinetin, a natural compound, can suppress the proliferation and invasiveness of GSCs and induce apoptosis in GSCs. Immunoblot analysis and luciferase assay revealed that Notch signaling was suppressed by alpinetin...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26681743/notch-signaling-exhibits-a-tumor-suppressor-function-in-gliomas
#13
(no author information available yet)
Loss of Notch signaling enhances the growth of PDGF-driven Trp53-null forebrain tumors.
February 2016: Cancer Discovery
https://www.readbyqxmd.com/read/26676446/anticancer-effect-of-eupatilin-on-glioma-cells-through-inhibition-of-the-notch-1-signaling-pathway
#14
Yawei Wang, Hongwei Hou, Ming Li, Yang Yang, Lan Sun
Eupatilin, one of the major flavonoids in Artemisia asiatica Nakai (Asteraceae), has been reported to possess antitumor properties. However, thus far there have been no reports regarding the effects of eupatilin on glioma. Therefore, in the current study the effects of eupatilin on glioma and the underlying molecular mechanism were explored. The effect of eupatilin on cell viability was detected by the MTT assay. Cell invasion and migration were performed with Transwell assays and cell apoptosis was determined by flow cytometric analysis...
February 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26669487/a-tumor-suppressor-function-for-notch-signaling-in-forebrain-tumor-subtypes
#15
Claudio Giachino, Jean-Louis Boulay, Robert Ivanek, Alvaro Alvarado, Cristobal Tostado, Sebastian Lugert, Jan Tchorz, Mustafa Coban, Luigi Mariani, Bernhard Bettler, Justin Lathia, Stephan Frank, Stefan Pfister, Marcel Kool, Verdon Taylor
In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jκ, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade...
December 14, 2015: Cancer Cell
https://www.readbyqxmd.com/read/26662803/aberrant-expression-of-notch1-hes1-and-dtx1-genes-in-glioblastoma-formalin-fixed-paraffin-embedded-tissues
#16
Rajeswari Narayanappa, Pritilata Rout, Madhuri G S Aithal, Ashis Kumar Chand
Glioblastoma is the most common malignant brain tumor accounting for more than 54 % of all gliomas. Despite aggressive treatments, median survival remains less than 1 year. This might be due to the unavailability of effective molecular diagnostic markers and targeted therapy. Thus, it is essential to discover molecular mechanisms underlying disease by identifying dysregulated pathways involved in tumorigenesis. Notch signaling is one such pathway which plays an important role in determining cell fates. Since it is found to play a critical role in many cancers, we investigated the role of Notch genes in glioblastoma with an aim to identify biomarkers that can improve diagnosis...
May 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26613556/targeting-notch-signaling-and-autophagy-increases-cytotoxicity-in-glioblastoma-neurospheres
#17
Manabu Natsumeda, Kosuke Maitani, Yang Liu, Hiroaki Miyahara, Harpreet Kaur, Qian Chu, Hongyan Zhang, Ulf Kahlert, Charles G Eberhart
Glioblastomas are highly aggressive tumors that contain treatment resistant stem-like cells. Therapies targeting developmental pathways such as Notch eliminate many neoplastic glioma cells, including those with stem cell features, but their efficacy can be limited by various mechanisms. One potential avenue for chemotherapeutic resistance is the induction of autophagy, but little is known how it might modulate the response to Notch inhibitors. We used the γ-secretase inhibitor (GSI) MRK003 to block Notch pathway activity in glioblastoma neurospheres and assessed effects on autophagy...
November 27, 2015: Brain Pathology
https://www.readbyqxmd.com/read/26600477/analysis-of-the-gene-protein-interaction-network-in-glioma
#18
C Zhou, W J Teng, J Zhuang, H L Liu, S F Tang, X J Cao, B N Qin, C C Wang, C G Sun
Glioma is the most aggressive type of brain tumor. Great progress has been achieved in glioma treatment, but the protein-protein interaction networks underlining glioma are poorly understood. We identified the protein-protein interaction network for glioma based on gene expression and predicted biological pathways underlying the molecular complexes in the network. Genes involved in glioma were selected from the Online Mendelian Inheritance in Man (OMIM) database. A literature search was performed using the Agilent Literature Search plugin, and Cytoscape was used to establish a protein-protein interaction network...
2015: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/26599017/increased-notch-signaling-enhances-radioresistance-of-malignant-stromal-cells-induced-by-glioma-stem-progenitor-cells
#19
Yuntian Shen, Hua Chen, Jinshi Zhang, Yanming Chen, Mengyao Wang, Jiawei Ma, Lei Hong, Ning Liu, Qiuhong Fan, Xueguan Lu, Ye Tian, Aidong Wang, Jun Dong, Qing Lan, Qiang Huang
BACKGROUND: Host malignant stromal cells induced by glioma stem/progenitor cells were revealed to be more radiation-resistant than the glioma stem/progenitor cells themselves after malignant transformation in nude mice. However, the mechanism underlying this phenomenon remains unclear. METHODS: Malignant stromal cells induced by glioma stem/progenitor cell 2 (GSC-induced host brain tumor cells, ihBTC2) were isolated and identified from the double color-coded orthotopic glioma nude mouse model...
2015: PloS One
https://www.readbyqxmd.com/read/26422827/alterations-in-cellular-metabolome-after-pharmacological-inhibition-of-notch-in-glioblastoma-cells
#20
Ulf D Kahlert, Menglin Cheng, Katharina Koch, Luigi Marchionni, Xing Fan, Eric H Raabe, Jarek Maciaczyk, Kristine Glunde, Charles G Eberhart
Notch signaling can promote tumorigenesis in the nervous system and plays important roles in stem-like cancer cells. However, little is known about how Notch inhibition might alter tumor metabolism, particularly in lesions arising in the brain. The gamma-secretase inhibitor MRK003 was used to treat glioblastoma neurospheres, and they were subdivided into sensitive and insensitive groups in terms of canonical Notch target response. Global metabolomes were then examined using proton magnetic resonance spectroscopy, and changes in intracellular concentration of various metabolites identified which correlate with Notch inhibition...
March 1, 2016: International Journal of Cancer. Journal International du Cancer
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