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Brain tumor stem cell

Takuichiro Hide, Yoshihiro Komohara, Yuko Miyasato, Hideo Nakamura, Keishi Makino, Motohiro Takeya, Jun-Ichi Kuratsu, Akitake Mukasa, Shigetoshi Yano
Glioblastoma (GBM) usually develops in adult brain white matter. Even after complete resection, GBM recurs around the tumor removal cavity, where GBM cells acquire chemo-radioresistance. Characterization of the tumor border microenvironment is critical for improving prognosis in patients with GBM. Here, we compared microRNA (miRNA) expression in samples from the tumor, tumor border, and periphery by miRNA microarray. The top three of miRNAs showing higher expression in the tumor border were related to oligodendrocyte differentiation, and pathologically oligodendrocyte lineage cells were increased in the border, where macrophages and microglia also colocalized...
March 1, 2018: EBioMedicine
Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yüng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanović, Michael Weller, Günter Eisele
Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues...
March 20, 2018: Acta Neuropathologica
Chun-Yuan Chen, Shan-Shan Rao, Lu Ren, Xiong-Ke Hu, Yi-Juan Tan, Yin Hu, Juan Luo, Yi-Wei Liu, Hao Yin, Jie Huang, Jia Cao, Zhen-Xing Wang, Zheng-Zhao Liu, Hao-Ming Liu, Si-Yuan Tang, Ran Xu, Hui Xie
Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses...
2018: Theranostics
Tao Wang, Zhong-Yi Qin, Liang-Zhi Wen, Yan Guo, Qin Liu, Zeng-Jie Lei, Wei Pan, Kai-Jun Liu, Xing-Wei Wang, Shu-Jie Lai, Wen-Jing Sun, Yan-Ling Wei, Lei Liu, Ling Guo, Yu-Qin Chen, Jun Wang, Hua-Liang Xiao, Xiu-Wu Bian, Dong-Feng Chen, Bin Wang
The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC)...
March 19, 2018: Cell Death and Differentiation
Even Hovig Fyllingen, Tor Ivar Hansen, Asgeir Store Jakola, Asta Kristine Håberg, Øyvind Salvesen, Ole Solheim
Background: Glioma is the most common primary brain tumor and is believed to arise from glial stem cells. Despite large efforts there are limited established risk factors. It has been suggested that tissue with more stem cells may exhibit higher risk of cancer due to chance alone. Assuming a positive correlation between the number of stem cell divisions in an organ and size of the same organ, we hypothesized that variation in intracranial volume, as a proxy for brain size may be linked to risk of high-grade glioma...
March 15, 2018: Neuro-oncology
Hyojin Eom, Neha Kaushik, Ki-Chun Yoo, Jin-Kyoung Shim, Munjin Kwon, Mi-Young Choi, Taeyoung Yoon, Seok-Gu Kang, Su-Jae Lee
Receptor tyrosine kinase Mer (MerTK) has been shown to be highly expressed in Glioblastoma multiforme (GBM) in comparison to its healthy counterpart and is implicated in brain tumorigenesis. Clarifying the underlying mechanism of MerTK induced invasiveness would result in novel strategies to improve patient's response to chemotherapeutics. In vitro and in vivo assays were performed to examine the functional role of cancer stem sell (CSC) maintenance in MerTK associated invasiveness. In this article, we demonstrate that apart from GBM cells, MerTK is also upregulated in GBM stem-like cells and associated with an increased infiltrative potential of brain tumors in vivo...
March 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Cindy R Timme, Barbara H Rath, John W O'Neill, Kevin Camphausen, Philip J Tofilon
Radiotherapy is a primary treatment modality for glioblastomas (GBMs). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSBs), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the radiosensitivity of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation...
March 16, 2018: Molecular Cancer Therapeutics
Bárbara da Silva, Ryan K Mathew, Euan S Polson, Jennifer Williams, Heiko Wurdak
Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs)...
March 1, 2018: SLAS Discovery
Nathália Kersting, Bárbara Kunzler Souza, Igor Araujo Vieira, Rafael Pereira Dos Santos, Danielly Brufatto Olguins, Lauro José Gregianin, André Tesainer Brunetto, Algemir Lunardi Brunetto, Rafael Roesler, Caroline Brunetto de Farias, Gilberto Schwartsmann
OBJECTIVE: Ewing sarcoma (ES) is a type of childhood cancer probably arising from stem mesenchymal or neural crest cells. The epidermal growth factor receptor (EGFR) acts as a driver oncogene in many types of solid tumors. However, its involvement in ES remains poorly understood. METHODS: Human SK-ES-1 and RD-ES ES cells were treated with EGF, the EGFR inhibitor tyrphostin (AG1478), or phosphoinositide 3-kinase (PI3K) or extracellular-regulated kinase (ERK)/mitogen-activated kinase (MAPK) inhibitors...
March 14, 2018: Oncology
Elizabeth Harford-Wright, Julie Gavard
Glioblastoma multiforme are mortifying brain tumors that contain a subpopulation of tumor cells with stem-like properties, termed as glioblastoma stem-like cells (GSCs). These GSCs constitute an autonomous reservoir of aberrant cells able to initiate, maintain, and repopulate the tumor mass. A new therapeutic strategy would consist of targeting the GSC population. The GSCs are situated in perivascular niches, closely associated with brain microvascular endothelial cells thereby involved in bidirectional molecular and cellular interactions...
2018: Journal of Experimental Neuroscience
Ryota Kurogi, Akira Nakamizo, Satoshi O Suzuki, Masahiro Mizoguchi, Koji Yoshimoto, Toshiyuki Amano, Takeo Amemiya, So Takagishi, Koji Iihara
OBJECTIVE Human bone marrow-derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may be a useful vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRNAs) have been shown to suppress the invasiveness of malignant gliomas. METHODS To test their potential to become vehicles for the delivery of miRNA to malignant gliomas, hMSCs were engineered so that hMSC secretion of miRNAs that inhibit glioma cell invasion was enabled without altering the hMSC tropism for glioma cells...
March 9, 2018: Journal of Neurosurgery
Fangjie Shao, Chong Liu
High-grade glioma, particularly, glioblastoma, is the most aggressive cancer of the central nervous system (CNS) in adults. Due to its heterogeneous nature, glioblastoma almost inevitably relapses after surgical resection and radio-/chemotherapy, and is thus highly lethal and associated with a dismal prognosis. Identifying the cell of origin has been considered an important aspect in understanding tumor heterogeneity, thereby holding great promise in designing novel therapeutic strategies for glioblastoma. Taking advantage of genetic lineage-tracing techniques, performed mainly on genetically engineered mouse models (GEMMs), multiple cell types in the CNS have been suggested as potential cells of origin for glioblastoma, among which adult neural stem cells (NSCs) and oligodendrocyte precursor cells (OPCs) are the major candidates...
2018: Frontiers in Molecular Neuroscience
Xue Cai, Michael E Sughrue
Glioblastoma (GBM) is the most invasive and devastating primary brain tumor with a median overall survival rate about 18 months with aggressive multimodality therapy. Its unique characteristics of heterogeneity, invasion, clonal populations maintaining stem cell-like cells and recurrence, have limited responses to a variety of therapeutic approaches, and have made GBM the most difficult brain cancer to treat. A great effort and progress has been made to reveal promising molecular mechanisms to target therapeutically...
February 6, 2018: Oncotarget
Thiago Verano-Braga, Vladimir Gorshkov, Sune Munthe, Mia D Sørensen, Bjarne W Kristensen, Frank Kjeldsen
Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells...
February 6, 2018: Oncotarget
Xinyi Jiang, Christine Wang, Sergio Fitch, Fan Yang
Hypoxia, a hallmark of malignant tumors, often correlates with increasing tumor aggressiveness and poor treatment outcomes. Due to a lack of vasculature, effective drug delivery to hypoxic tumor regions remains challenging. Signaling through the chemokine SDF-1α and its receptor CXCR4 plays a critical role in the homing of stem cells to ischemia for potential use as drug-delivery vehicles. To harness this mechanism for targeting tumor hypoxia, we developed polymeric nanoparticle-induced CXCR4-overexpressing human adipose-derived stem cells (hADSCs)...
2018: Theranostics
Tao Zhang, Pan Wang, Yanxia Liu, Jiankang Zhou, Zhenqing Shi, Kang Cheng, Tuanjie Huang, Xinxin Wang, Greta Luyuan Yang, Bo Yang, Shanshan Ma, Fangxia Guan
Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines...
March 3, 2018: Cell and Tissue Research
Kenny Kwok-Hei Yu, Jessica T Taylor, Omar N Pathmanaban, Amir Saam Youshani, Deniz Beyit, Joanna Dutko-Gwozdz, Roderick Benson, Gareth Griffiths, Ian Peers, Peter Cueppens, Brian A Telfer, Kaye J Williams, Catherine McBain, Ian D Kamaly-Asl, Brian W Bigger
BACKGROUND: Glioblastoma (GBM) is the most common primary brain malignancy in adults, yet survival outcomes remain poor. First line treatment is well established, however disease invariably recurs and improving prognosis is challenging. With the aim of personalizing therapy at recurrence, we have established a high content screening (HCS) platform to analyze the sensitivity profile of seven patient-derived cancer stem cell lines to 83 FDA-approved chemotherapy drugs, with and without irradiation...
2018: PloS One
Hila Rosenfeld-Keidar, Rinat Eshel, Aviva Pinhasov, Menachem Bitan, Sabina Edelman, Marcela Broitman, Rina Dvir, Efraim Sadot, Dror Levin, Michal Manisterski, Sivan Berger-Achituv, Ronit Elhasid
Numerous adults' studies demonstrated that preaphaeresis CD34+ cells significantly correlate with the number of CD34+ cells collected by the aphaeresis procedure. Equivalent studies in children are scarce. We studied retrospectively 92 aphaeresis procedures performed following chemotherapy (44) or in steady state (48) in 60 pediatric patients (40 males, 20 females), median age of 7.5 years. Aphaeresis procedures were performed using a SPECTRA Optica (TERUMOBCT) continuous flow cell separator. CD34+ cell concentrations were assessed using flow cytometry...
March 2, 2018: Pediatric Transplantation
Claudio Festuccia, Andrea Mancini, Alessandro Colapietro, Giovanni Luca Gravina, Flora Vitale, Francesco Marampon, Simona Delle Monache, Simona Pompili, Loredana Cristiano, Antonella Vetuschi, Vincenzo Tombolini, Yi Chen, Thomas Mehrling
BACKGROUND: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity...
February 27, 2018: Journal of Hematology & Oncology
Patricia Giuliani, Mariachiara Zuccarini, Marzia Carluccio, Sihana Ziberi, Patrizia Di Iorio, Francesco Caciagli, Renata Ciccarelli
BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal brain malignancy. Recent evidence suggests that the presence of stem-like cells (GSCs) inside the tumor with high self-renewal, resistance to chemotherapy and invasiveness/migration potential is associated with poor GBM prognosis. GSC aggressiveness seems to be linked to an important process involved in tumorigenesis and cancer metastasis called epithelial-to-mesenchymal transition (EMT), which is responsible for several biochemical changes and the acquisition of a more mesenchymal phenotype by GSCs, that enhance their migration, invasiveness and resistance to apoptosis...
February 26, 2018: Current Drug Targets
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