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Brain tumor stem cell

Y-Q Li, Zw-C Cheng, Sk-W Liu, I Aubert, C S Wong
Inhibition of hippocampal neurogenesis is implicated in neurocognitive dysfunction after cranial irradiation for brain tumors. How irradiation results in impaired neuronal development remains poorly understood. The Trp53 (p53) gene is known to regulate cellular DNA damage response after irradiation. Whether it has a role in disruption of late neuronal development remains unknown. Here we characterized the effects of p53 on neuronal development in adult mouse hippocampus after irradiation. Different bromodeoxyuridine incorporation paradigms and a transplantation study were used for cell fate mapping...
2016: Cell Death Discovery
Igor S Bryukhovetskiy, Inessa V Dyuizen, Valeriy E Shevchenko, Andrey S Bryukhovetskiy, Polina V Mischenko, Elena V Milkina, Yuri S Khotimchenko
Glioblastoma multiforme is an aggressive malignant brain tumor with terminal consequences. A primary reason for its resistance to treatment is associated with cancer stem cells (CSCs), of which there are currently no effective ways to destroy. It remains unclear what cancer cells become a target of stem cell migration, what the role of this process is in oncogenesis and what stem cell lines should be used in developing antitumor technologies. Using modern post‑genome technologies, the present study investigated the migration of human stem cells to cancer cells in vitro, the comparative study of cell proteomes of certain stem cells (including CSCs) was conducted and stem cell migration in vivo was examined...
October 13, 2016: Molecular Medicine Reports
Yu Shi, Wenchao Zhou, Lin Cheng, Cong Chen, Zhi Huang, Xiaoguang Fang, Qiulian Wu, Zhicheng He, Senlin Xu, Justin D Lathia, Yifang Ping, Jeremy N Rich, Xiu-Wu Bian, Shideng Bao
Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the pro-survival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation to facilitate the STAT3 activation in GSCs...
October 14, 2016: Cell Death and Differentiation
Heather Marion Ames, Ming Yuan, Maria Adelita Vizcaíno, Wayne Yu, Fausto J Rodriguez
Low-grade (WHO I-II) gliomas and glioneuronal tumors represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression/translation that can repress multiple mRNAs concurrently through base pairing, and have an important role in cancer, including brain tumors...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Sophie Guelfi, Hugues Duffau, Luc Bauchet, Bernard Rothhut, Jean-Philippe Hugnot
Glioblastomas are devastating and extensively vascularized brain tumors from which glioblastoma stem-like cells (GSCs) have been isolated by many groups. These cells have a high tumorigenic potential and the capacity to generate heterogeneous phenotypes. There is growing evidence to support the possibility that these cells are derived from the accumulation of mutations in adult neural stem cells (NSCs) as well as in oligodendrocyte progenitors. It was recently reported that GSCs could transdifferentiate into endothelial-like and pericyte-like cells both in vitro and in vivo, notably under the influence of Notch and TGFβ signaling pathways...
2016: Stem Cells International
Amanda L Rinkenbaugh, Patricia C Cogswell, Barbara Calamini, Denise E Dunn, Anders I Persson, William A Weiss, Donald C Lo, Albert S Baldwin
Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. Glioblastoma stem cells (GSCs) drive tumor formation, invasion, and drug resistance and, as such, are the focus of studies to identify new therapies for disease control. Here, we identify the involvement of IKK and NF-κB signaling in the maintenance of GSCs. Inhibition of this pathway impairs self-renewal as analyzed in tumorsphere formation and GBM expansion as analyzed in brain slice culture. Interestingly, both the canonical and non-canonical branches of the NF-κB pathway are shown to contribute to this phenotype...
October 6, 2016: Oncotarget
Xingliang Dai, Cheng Ma, Qing Lan, Tao Xu
Glioma is still difficult to treat because of its high malignancy, high recurrence rate, and high resistance to anticancer drugs. An alternative method for research of gliomagenesis and drug resistance is to use in vitro tumor model that closely mimics the in vivo tumor microenvironment. In this study, we established a 3D bioprinted glioma stem cell model, using modified porous gelatin/alginate/fibrinogen hydrogel that mimics the extracellular matrix. Glioma stem cells achieved a survival rate of 86.92%, and proliferated with high cellular activity immediately following bioprinting...
October 11, 2016: Biofabrication
Anning Li, Yue Wu, Jenny Linnoila, Benjamin Pulli, Cuihua Wang, Matthias Zeller, Muhammad Ali, Grant K Lewandrowski, Jinghui Li, Benoit Tricot, Edmund Keliher, Gregory R Wojtkiewicz, Giulia Fulci, Xiaoyuan Feng, Bakhos A Tannous, Zhenwei Yao, John W Chen
Currently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin-streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA-Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P < 0...
October 8, 2016: Cancer Immunology, Immunotherapy: CII
Ulysse Gimenez, Adriana-T Perles-Barbacaru, Arnaud Millet, Florence Appaix, Michele El-Atifi, Karin Pernet-Gallay, Boudewijn van der Sanden, François Berger, Hana Lahrech
Monitoring glioma cell infiltration in the brain is critical for diagnosis and therapy. Using a new glioma Glio6 mouse model derived from human stem cells we show how diffusion tensor imaging (DTI) may predict glioma cell migration/invasion. In vivo multiparametric MRI was performed at one, two and three months of Glio6 glioma growth (Glio6 (n = 6), sham (n = 3)). This longitudinal study reveals the existence of a time window to study glioma cell/migration/invasion selectively. Indeed, at two months only Glio6 cell invasion was detected, while tumor mass formation, edema, blood-brain barrier leakage and tumor angiogenesis were detected later, at three months...
September 15, 2016: NMR in Biomedicine
Xinhui Wang, Ming Hu, Feifei Xing, Mengyuan Wang, Bing Wang, Dongmeng Qian
Glioblastoma (GBM) are the most common and aggressive tumors of human brain. Recent studies showed that human cytomegalovirus (HCMV) can induce malignant transformation of tumor cells to maintain stemness. Transcription factor 5 (ATF5) is an anti-apoptotic protein that is highly expressed in malignant glioma. The aim of this study is to investigate the effect of HCMV infection on the stem cell makers of U251 cells. U251 cells were infected by AD169 HCMV strain (MOI = 1). The expression of stem cell makers (CD133, NES, Notch1) in infected U251 cells were compared with the expression in uninfected U251 cell to see the difference between them...
October 7, 2016: Journal of Medical Virology
Mariana Maier Gaelzer, Mariana Silva Dos Santos, Bárbara Paranhos Coelho, Alice Hoffman de Quadros, Fabrício Simão, Vanina Usach, Fátima Costa Rodrigues Guma, Patrícia Setton-Avruj, Guido Lenz, Christianne G Salbego
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment, and poor outcome. However, there is lack of studies relating type of cell death, status of Akt phosphorylation on Ser473, mitochondrial membrane potential, and morphological changes of tumor cells after hypoxia and reoxygenation. The rat glioma C6 cell line was exposed to oxygen deprivation (OD) in 5 % fetal bovine serum (FBS) or serum-free media followed by reoxygenation (RO)...
October 6, 2016: Molecular Neurobiology
Zheng-Nan Shan, Rui Tian, Min Zhang, Zhao-Hua Gui, Jing Wu, Min Ding, Xin-Fu Zhou, Jie He
MicroRNA128-1 (miR128-1), as a brain-specific miRNA, is downregulated in glioblastoma multiforme (GBM) and closely associated with the progression of GBM. However, the underlying molecular mechanism of the downregulation and its role in the regulation of tumorigenesis and anticancer drug resistance in GBM remains largely unknown. In the current study,we found that miR128-1 was downregulated in GBM and glioma stem-like cells (GSCs). Intriguingly, treatment with the DNA methylation inhibitors 5-Aza-CdR (Aza) and 4-phenylbutyric acid (PBA) resulted in miR128-1 upregulation in both GBM cells and GSCs...
October 1, 2016: Oncotarget
Katharina Koch, Rudolf Hartmann, Friederike Schröter, Abigail Kora Suwala, Donata Maciaczyk, Andrea Caroline Krüger, Dieter Willbold, Ulf Dietrich Kahlert, Jaroslaw Maciaczyk
Glioblastoma (GBM) is the most malignant brain tumor with very limited therapeutic options. Standard multimodal treatments, including surgical resection and combined radio-chemotherapy do not target the most aggressive subtype of glioma cells, brain tumor stem cells (BTSCs). BTSCs are thought to be responsible for tumor initiation, progression, and relapse. Furthermore, they have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT) thereby inducing tumor dissemination and chemo resistance...
September 29, 2016: Oncotarget
Abdolali Amiri, Phuong Uyen Le, Alexandre Moquin, Gayane Machkalyan, Kevin Petrecca, John W Gillard, Nathan Yoganathan, Dusica Maysinger
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme upregulated in several types of tumors including glioblastoma multiforme (GBM). GBM is among the most aggressive tumors among gliomas. Temozolomide (TMZ) therapy combined with surgical or radiation approaches are standard treatments but not effective in long term. In this study we tested the treatment with acetazolamide (ATZ), an inhibitor of CAIX, alone or combined with TMZ. The experiments were performed in 2D and 3D cultures (spheroids) using glioblastoma U251N and human brain tumor stem cells (BTSC)...
October 1, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Tina Zimmermann, Floortje Remmers, Beat Lutz, Julia Leschik
Huntington's disease (HD) is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor). By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA) chemical and two genetic HD mouse models (R6/2 and N171-82Q) on the basis of distinct behavioral parameters, including CatWalk gait analysis...
October 11, 2016: Stem Cell Reports
D Raleigh, B Tomlin, B Del Buono, E Roddy, K Sear, L Byer, E Felton, A Banerjee, J Torkildson, D Samuel, B Horn, S E Braunstein, D A Haas-Kogan, S Mueller
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Arlet M Acanda de la Rocha, Hernando López-Bertoni, Elizabeth Guruceaga, Marisol González-Huarriz, Naiara Martínez-Vélez, Enric Xipell, Juan Fueyo, Candelaria Gomez-Manzano, Marta M Alonso
INTRODUCTION: Glioblastoma is the most malignant brain tumor in adults and is associated with poor survival despite multimodal treatments. Glioma stem-like cells (GSCs) are cells functionally defined by their self-renewal potential and the ability to reconstitute the original tumor upon orthotopic implantation. They have been postulated to be the culprit of glioma chemo- and radio-resistance ultimately leading to relapse. Understanding the molecular circuits governing the GSC compartment is essential...
2016: PloS One
Tanwarat Sanvoranart, Aungkura Supokawej, Pakpoom Kheolamai, Yaowalak U-Pratya, Niphon Poungvarin, Sith Sathornsumetee, Surapol Issaragrisil
Glioblastoma (GBM) is an aggressive malignant brain tumor that still lacks effective therapy. Glioblastoma stem cells (GBM-SCs) were identified to contribute to aggressive phenotypes and poor clinical outcomes for GBM. Netrin-1, an axon guidance molecule, has been found in several tumors in adults. However, the role of Netrin-1 in GBM-SCs remains largely unknown. In this study, CD133-positive U251 GBM cells were used as a putative GBM-SC population to identify the functions of Netrin-1. Using lentiviral transduction, Netrin-1 miR RNAi vectors were transduced into CD133-positive U251 cells...
September 20, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Vivian Adamski, Anne Dorothée Schmitt, Charlotte Flüh, Michael Synowitz, Kirsten Hattermann, Janka Held-Feindt
Gliomas are the most common primary brain tumors. The most malignant form, the glioblastomas (GBMs, WHO IV), are characterized by an invasive phenotype, which enables the tumor cells to infiltrate into adjacent brain tissue. When investigating GBM migration and invasion properties in vitro, in most cases GBM cell lines were analyzed. Comprehensive investigations focusing on progression-dependent characteristics of migration processes using fresh human glioma samples of different malignancy grades do not exist...
September 16, 2016: Oncology Research
Alexander Birbrair, Anirudh Sattiraju, Dongqin Zhu, Gilberto Zulato, Izadora Batista, Van T Nguyen, Maria Laura Messi, Kiran Kumar Solingapuram Sai, Frank C Marini, Osvaldo Delbono, Akiva Mintz
: : Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary malignant adult brain tumor characterized by extensive invasiveness, heterogeneity, and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be only marginally effective in treating GBM because of its invasive nature. Therefore, extensive efforts have been put forth to develop tumor-tropic stem cells as viable therapeutic vehicles with potential to treat even the most invasive tumor cells that are harbored within areas of normal brain...
September 14, 2016: Stem Cells Translational Medicine
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