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notch signaling in glioma

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https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#1
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 1, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28416488/activation-of-notch-signaling-by-tenascin-c-promotes-growth-of-human-brain-tumor-initiating-cells
#2
Susobhan Sarkar, Reza Mirzaei, Franz J Zemp, Wu Wei, Donna L Senger, Stephen M Robbins, V Wee Yong
Oncogenic signaling by NOTCH is elevated in brain tumor-initiating cells (BTIC) in malignant glioma, but the mechanism of its activation is unknown. Here we provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increases NOTCH activity in BTIC to promote their growth. We demonstrate the proximal localization of TNC and BTIC in human glioblastoma specimens and in orthotopic murine xenografts of human BTIC implanted intracranially. In tissue culture, TNC was superior amongst several extracellular matrix proteins in enhancing the sphere-forming capacity of glioma patient-derived BTIC...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28380416/actin-cytoskeleton-regulator-arp2-3-complex-is-required-for-dll1-activating-notch1-signaling-to-maintain-the-stem-cell-phenotype-of-glioma-initiating-cells
#3
Chen Zhang, Long Hai, Meng Zhu, Shengping Yu, Tao Li, Yu Lin, Bo Liu, Xingchen Zhou, Lei Chen, Pengfei Zhao, Hua Zhou, Yubao Huang, Kai Zhang, Bingcheng Ren, Xuejun Yang
Glioblastoma (GBM) is the most common and lethal primary intracranial tumor. Actin cytoskeleton regulator Arp2/3 complex stimulates glioma cell motility and migration, and thus triggers tumor invasion. However, little is known regarding the role of actin cytoskeleton in maintaining the stem cell phenotype. Here, we showed that Arp2/3 complex improved stem cell phenotype maintenance through sustaining the activated Notch signaling. ShRNA targeting Notch ligand Delta-like 1 (DLL1) decreased CD133 and Nestin expression, and impaired the self-renewal ability of CD133+ U87-MG and U251-MG glioma cells, indicating DLL1/Notch1 signaling promoted stem cell phenotype maintenance...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28325280/mir-134-a-human-cancer-suppressor
#4
REVIEW
Jing-Yu Pan, Feng Zhang, Cheng-Cao Sun, Shu-Jun Li, Guang Li, Feng-Yun Gong, Tao Bo, Jing He, Rui-Xi Hua, Wei-Dong Hu, Zhan-Peng Yuan, Xin Wang, Qi-Qiang He, De-Jia Li
MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28259943/sclareolide-enhances-gemcitabine%C3%A2-induced-cell-death-through-mediating-the-nicd-and-gli1-pathways-in-gemcitabine%C3%A2-resistant-human-pancreatic-cancer
#5
Sheng Chen, Ye Wang, Wen-Long Zhang, Mao-Sheng Dong, Jian-Hua Zhang
Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs)...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255276/melatonin-inhibits-glioblastoma-stem-like-cells-through-suppression-of-ezh2-notch1-signaling-axis
#6
Xiangrong Zheng, Bo Pang, Guangyan Gu, Taihong Gao, Rui Zhang, Qi Pang, Qian Liu
Glioblastoma stem-like cells (GSCs) play essential roles in glioma growth, radio- and chemo-resistance, and recurrence. Elimination of GSCs has therefore become a key strategy and challenge in glioblastoma therapy. Here, we show that melatonin, an indolamine derived from I-tryptophan, significantly inhibited viability and self-renewal ability of GSCs accompanied by a decrease of stem cell markers. We have identified EZH2-NOTCH1 signaling as the key signal pathway that regulated the effects of melatonin in the GSCs...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28216164/conversion-of-glioma-cells-to-glioma-stem-like-cells-by-angiocrine-factors
#7
Jun-Kyum Kim, Hye-Min Jeon, Hee-Young Jeon, Se-Yeong Oh, Eun-Jung Kim, Xiong Jin, Se-Hoon Kim, Sung-Hak Kim, Xun Jin, Hyunggee Kim
Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28081466/long-non-coding-rna-zfas1-is-an-unfavourable-prognostic-factor-and-promotes-glioma-cell-progression-by-activation-of-the-notch-signaling-pathway
#8
Kai Gao, Zhiwu Ji, Kun She, Qingyan Yang, Lianbin Shao
Survival of patients with glioma remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play key roles in tumor initiation and progression. However, the function of lncRNA ZFAS1 in glioma is still unclear. In the current study, we found that ZFAS1 was upregulated in glioma tissues and cell lines. High ZFAS1 expression in glioma tissues was significantly correlated with advanced tumor stage and poor overall survival. Furthermore, in vitro assays demonstrated that ZFAS1 inhibition significantly suppressed glioma cell proliferation, migration and invasion...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#9
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28060761/identification-of-micrornas-associated-with-glioma-diagnosis-and-prognosis
#10
Xinyun Ye, Wenjin Wei, Zhengyu Zhang, Chunming He, Ruijin Yang, Jinshi Zhang, Zhiwu Wu, Qianliang Huang, Qiuhua Jiang
The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#11
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27858266/reverse-phase-protein-arrays-enable-glioblastoma-molecular-subtyping
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
January 2017: 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
#20
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
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