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https://www.readbyqxmd.com/read/28748212/genetically-engineered-multilineage-differentiating-stress-enduring-cells-as-cellular-vehicles-against-malignant-gliomas
#1
Tomohiro Yamasaki, Shohei Wakao, Hiroshi Kawaji, Shinichiro Koizumi, Tetsuro Sameshima, Mari Dezawa, Hiroki Namba
Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, which are endogenous non-tumorigenic pluripotent-like stem cells that are easily collectable from the bone marrow as SSEA-3(+) cells, as carriers of the HSVtk gene...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28740831/the-impact-of-the-tumor-microenvironment-on-the-properties-of-glioma-stem-like-cells
#2
REVIEW
Alessandra Audia, Siobhan Conroy, Rainer Glass, Krishna P L Bhat
Glioblastoma is the most common and highly malignant primary brain tumor, and patients affected with this disease exhibit a uniformly dismal prognosis. Glioma stem-like cells (GSCs) are a subset of cells within the bulk tumor that possess self-renewal and multi-lineage differentiation properties similar to somatic stem cells. These cells also are at the apex of the cellular hierarchy and cause tumor initiation and expansion after chemo-radiation. These traits make them an attractive target for therapeutic development...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28734730/multifaceted-c-x-c-chemokine-receptor-4-inhibition-interferes-with-anti-vascular-endothelial-growth-factor-therapy-induced-glioma-dissemination
#3
Jean-Pierre Gagner, Yasmeen Sarfraz, Valerio Ortenzi, Fawaz M Alotaibi, Luis A Chiriboga, Awab T Tayyib, Garry J Douglas, Eric Chevalier, Barbara Romagnoli, Gérald Tuffin, Michel Schmitt, Guillaume Lemercier, Klaus Dembowsky, David Zagzag
Resistance to antiangiogenic therapy glioblastoma (GBM) patients may involve hypoxia-induced expression of stromal cell-derived factor (SDF)-1α receptor C-X-C chemokine receptor 4 (CXCR4) on invading tumor, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with peptide epitope mimetic POL5551 disrupts anti-vascular endothelial growth factor therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-vascular endothelial growth factor antibody B20-4...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28731079/a-polymeric-temozolomide-nanocomposite-against-orthotopic-glioblastoma-xenograft-tumor-specific-homing-directed-by-nestin
#4
Suma Prabhu, Jayant Sastri Goda, Srinivas Mutalik, Bhabani Shankar Mohanty, Pradip Chaudhari, Sharada Rai, Nayanabhirama Udupa, Bola Sadashiva Satish Rao
The development of effective therapeutic strategies for glioblastoma faces challenges such as modulating the blood brain barrier (BBB) for drug influx and selectively targeting tumor cells. Nanocarrier drug delivery strategies are functionalized to enhance vascular permeability. We engineered superparamagnetic iron oxide nanoparticle (SPION) based polymeric nanocomposites (84.37 ± 12.37 nm / 101.56 ± 7.42 nm) embedding temozolomide (TMZ) targeted against glioblastoma by tagging an antibody against nestin, a stem cell marker, and transferrin / polysorbate-80 to permeate the BBB...
July 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28728846/the-effects-of-type-i-interferon-on-glioblastoma-cancer-stem-cells
#5
Ziyun Du, Chun Cai, Michelle Sims, Frederick A Boop, Andrew M Davidoff, Lawrence M Pfeffer
Glioblastomas (GBMs) are highly invasive brain tumors that are extremely deadly. The highly aggressive nature of GBM as well as its heterogeneity at the molecular and cellular levels has been attributed to a rare subpopulation of GBM stem-like cells (GSCs). Interferons (IFNs) are a family of endogenous antiviral proteins that have anticancer activity in vitro, and have been used clinically to treat GBM. IFN inhibits the proliferation of various established GBM cell lines, but the effects of IFNs on GSCs remain relatively unknown...
July 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28727574/flexible-ligated-ruthenium-ii-self-assemblies-sensitizes-glioma-tumor-initiating-cells-in-vitro
#6
Palani Elumalai, Neha Kaushik, Dong Hwan Kim, Hyunuk Kim, Su Jae Lee, Eun Ha Choi, Ki-Whan Chi, Nagendra Kumar Kaushik
The tumorigenic potentials of residual cancer stem-like cells within tumors represent limitations of current cancer therapies. Here, the authors describe the effects of synthesized flexible, ligated, supramolecular self-assembled chair type tetranuclear ruthenium (II) metallacycles (2-5) on glioblastoma and glioma stem like cells. These self-assemblies were observed to be selectively toxic to glioma cells and CD133-positive glioma stem like cells population. Of the self-assembled compounds tested, metallacycle 4 more efficiently induced glioma stem like cells death within a brain cancer cell population and simultaneously inhibited the formation of free-floating gliospheres by reducing the sphere size...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723673/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#7
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718448/neuronal-activity-in-ontogeny-and-oncology
#8
REVIEW
Humsa Venkatesh, Michelle Monje
The nervous system plays a central role in regulating the stem cell niche in many organs, and thereby pivotally modulates development, homeostasis, and plasticity. A similarly powerful role for neural regulation of the cancer microenvironment is emerging. Neurons promote the growth of cancers of the brain, skin, prostate, pancreas, and stomach. Parallel mechanisms shared in development and cancer suggest that neural modulation of the tumor microenvironment may prove a universal theme, although the mechanistic details of such modulation remain to be discovered for many malignancies...
February 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718304/the-role-of-surgery-in-low-grade-gliomas-do-timing-and-extent-of-resection-matter
#9
Hugues Duffau
Hugues Duffau is a Professor and Chairman of the Neurosurgery Department in the Montpellier University Medical Center and Head of the INSERM 1051 Team "plasticity of the central nervous system, human stem cells and glial tumors" at the Institute for Neurosciences of Montpellier (France). He is an expert in the awake cognitive neurosurgery of slow-growing brain tumors, such as low-grade gliomas, a routine which he has developed since 20 years. His fundamental approach is centered on the concepts of the brain connectomics and neuroplasticity, breaking with the traditional localizationist view of cerebral processing...
July 18, 2017: CNS Oncology
https://www.readbyqxmd.com/read/28710771/detailed-longitudinal-sampling-of-glioma-stem-cells-in-situ-reveals-chr7-gain-and-chr10-loss-as-repeated-events-in-primary-tumor-formation-and-recurrence
#10
Mehmet Baysan, Kevin Woolard, Margaret C Cam, Wei Zhang, Hua Song, Svetlana Kotliarova, Demosthenes Balamatsias, Amanda Linkous, Susie Ahn, Jennifer Walling, Galina I Belova, Howard A Fine
Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation as well as in response to therapeutic intervention, can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, as well as from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence...
July 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#11
Wanlu Du, Ivan Seah, Oumaima Bougazzoul, GiHun Choi, Katrina Meeth, Marcus W Bosenberg, Hiroaki Wakimoto, David Fisher, Khalid Shah
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs)...
July 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28703798/mtorc2-regulates-hedgehog-pathway-activity-by-promoting-stability-to-gli2-protein-and-its-nuclear-translocation
#12
Samarpan Maiti, Susmita Mondal, Eswara M Satyavarapu, Chitra Mandal
mTORC2 is aberrantly activated in cancer and therefore is considered to be an important therapeutic target. The hedgehog pathway, which is also often hyperactivated, regulates transcription of several genes associated with angiogenesis, metastasis, cellular proliferation and cancer stem cell (CSC) regeneration. However, the contribution of mTORC2 toward hedgehog pathway activity has not been explored yet. Here we have addressed the molecular cross talk between mTORC2 and hedgehog pathway activities in the context of glioblastoma multiforme, a malignant brain tumor using as a model system...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28695794/the-natural-component-isolated-from-enterolobium-contortisiliquum-impairs-brain-tumors-and-affects-their-interactions-with-mesenchymal-stem-cells
#13
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Costa, Heron Fernandes Vieira Torquato, Natália Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with an overall patient survival of about 16 months. Thus, natural compounds with anti-cancer properties are gaining attention as possible alternatives for GBM treatment. Studies in various cancer models have shown the anti-cancer effects of the Enterolobium contortisiliquum Trypsin Inhibitor (EcTI). Here, we investigated the outcomes of EcTI on U87 cells, mesenchymal stem cells (MSC), and their direct cocultures (U87/MSC). MSC are present in tumor stroma and represent a potential drug delivery vehicle as the result of their tumor tropism...
July 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28693365/behavior-of-xeno-transplanted-undifferentiated-human-induced-pluripotent-stem-cells-is-impacted-by-microenvironment-without-evidence-of-tumors
#14
Veronica Martinez-Cerdeno, Bonnie Barrilleaux, Ashley McDonough, Jeanelle Ariza, Benjamin Yuen, Priyanka Somanath, Catherine Le, Craig Steward, Kayla Horton, Paul Knoepfler
Human pluripotent stem cells (hPSC) have great clinical potential via the use of their differentiated progeny, a population in which there is some concern over risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC. Preclinical studies using human stem cells are most often performed within a xenotransplant context. Here, we sought to measure how undifferentiated hPSC behave following xenotransplant. We directly transplanted undifferentiated human induced pluripotent and embryonic stem cells (hIPSC; hESC) into the adult mouse brain ventricle and analyzed their fates...
July 10, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28687615/sox5-6-21-prevent-oncogene-driven-transformation-of-brain-stem-cells
#15
Idha Kurtsdotter, Danijal Topcic, Alexandra Karlén, Bhumica Singla, Daniel W Hagey, Maria Bergsland, Peter Siesjö, Monica Nistér, Joseph W Carlson, Veronique Lefebvre, Oscar Persson, Johan Holmberg, Jonas Muhr
Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6 and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, while genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28687443/ganglioglioma-of-brain-stem-and-cervicomedullary-junction-a-50years-review-of-literature
#16
REVIEW
M Burhan Janjua, Iryna Ivasyk, David J Pisapia, Mark M Souweidane
Gangliogliomas are rare low-grade brain tumors composed of both neoplastic glial and neuronal cell elements. The treatment modalities are relatively different in this location and hence factors affecting outcome are poorly understood. We identified 142 brain stem GG patients across 46 studies. The average age was 11.4years with significant difference b/w males and females under the age of 20 (p=0.001). 100% of tumors in the CMJ while, 72% of type I and 86% of type II tumors demonstrated contrast enhancement...
July 4, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28687190/a-synthetic-bmp-2-mimicking-peptide-induces-glioblastoma-stem-cell-differentiation
#17
Elena Rampazzo, Monica Dettin, Francesca Maule, Alessandra Scabello, Luisa Calvanese, Gabriella D'Auria, Lucia Falcigno, Elena Porcù, Annj Zamuner, Alessandro Della Puppa, Daniele Boso, Giuseppe Basso, Luca Persano
BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain tumor, characterized by the intrinsic resistance to chemotherapy due to the presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC differentiation and to sensitize GBM cells to treatments. METHODS: The BMP-2 mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc chemistry...
July 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28678747/targeting-intercellular-adhesion-molecule-1-prolongs-survival-in-mice-bearing-bevacizumab-resistant-glioblastoma
#18
Yuji Piao, Verlene Henry, Ningyi Tiao, Soon Young Park, Juan Martinez-Ledesma, Jian Wen Dong, Veerakumar Balasubramaniyan, John F de Groot
Intercellular cell adhesion molecule 1 (ICAM-1; also known as CD54) is overexpressed in bevacizumab-resistant glioblastoma. In the present study, we tested our hypothesis that highly expressed ICAM-1 mediates glioblastoma's resistance to antiangiogenic therapy. We validated ICAM-1 overexpression in tumors resistant to antiangiogenic therapy using real-time polymerase chain reaction, immunohistochemistry, and Western blotting. We also detected ICAM1 expression in most glioma stem cells (GSCs). We investigated the mechanism of ICAM-1 overexpression after bevacizumab treatment and found that ICAM-1 protein expression was markedly increased in a time-dependent manner in GSC11 and GSC17 cells under hypoxic conditions in vitro...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28677106/expression-and-prognostic-value-of-jam-a-in-gliomas
#19
Ann Mari Rosager, Mia D Sørensen, Rikke H Dahlrot, Henning B Boldt, Steinbjørn Hansen, Justin D Lathia, Bjarne W Kristensen
Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas...
July 4, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28670569/molecular-and-microenvironmental-determinants-of-glioma-stem-like-cell-survival-and-invasion
#20
REVIEW
Alison Roos, Zonghui Ding, Joseph C Loftus, Nhan L Tran
Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults with a 5-year survival rate of 5% despite intensive research efforts. The poor prognosis is due, in part, to aggressive invasion into the surrounding brain parenchyma. Invasion is a complex process mediated by cell-intrinsic pathways, extrinsic microenvironmental cues, and biophysical cues from the peritumoral stromal matrix. Recent data have attributed GBM invasion to the glioma stem-like cell (GSC) subpopulation. GSCs are slowly dividing, highly invasive, therapy resistant, and are considered to give rise to tumor recurrence...
2017: Frontiers in Oncology
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