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https://www.readbyqxmd.com/read/29890725/new-tetrahydroisoquinoline-derivatives-overcome-pgp-activity-in-brain-blood-barrier-and-glioblastoma-multiforme-in-vitro
#1
Iris Chiara Salaroglio, Elena Gazzano, Joanna Kopecka, Konstantin Chegaev, Costanzo Costamagna, Roberta Fruttero, Stefano Guglielmo, Chiara Riganti
P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs used against glioblastoma multiforme (GB). Indeed, Pgp is highly expressed in GB stem cells and in the brain-blood barrier (BBB), the peculiar endothelium surrounding the brain. Inhibiting Pgp activity in the BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC50 for Pgp ≤ 50 nM, in primary human BBB cells and in patient-derived GB samples, from which we isolated differentiated/adherent cells (AC, i...
June 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29887596/yap-and-mrtf-a-transcriptional-co-activators-of-rhoa-mediated-gene-expression-are-critical-for-glioblastoma-tumorigenicity
#2
Olivia M Yu, Jorge A Benitez, Steven W Plouffe, Daniel Ryback, Andrea Klein, Jeff Smith, Jason Greenbaum, Benjamin Delatte, Anjana Rao, Kun-Liang Guan, Frank B Furnari, Olga Meiri Chaim, Shigeki Miyamoto, Joan Heller Brown
The role of YAP (Yes-associated protein 1) and MRTF-A (myocardin-related transcription factor A), two transcriptional co-activators regulated downstream of GPCRs (G protein-coupled receptors) and RhoA, in the growth of glioblastoma cells and in vivo glioblastoma multiforme (GBM) tumor development was explored using human glioblastoma cell lines and tumor-initiating cells derived from patient-derived xenografts (PDX). Knockdown of these co-activators in GSC-23 PDX cells using short hairpin RNA significantly attenuated in vitro self-renewal capability assessed by limiting dilution, oncogene expression, and neurosphere formation...
June 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29885287/cellular-fate-decisions-in-the-developing-female-anteroventral-periventricular-nucleus-are-regulated-by-canonical-notch-signaling
#3
Matthew J Biehl, Kerim B Kaylan, Robert J Thompson, Rachel V Gonzalez, Karen E Weis, Gregory H Underhill, Lori T Raetzman
The hypothalamic anteroventral periventricular nucleus (AVPV) is the major regulator of reproductive function within the hypothalamic-pituitary-gonadal (HPG) axis. Despite an understanding of the function of neuronal subtypes within the AVPV, little is known about the molecular mechanisms regulating their development. Previous work from our laboratory has demonstrated that Notch signaling is required in progenitor cell maintenance and formation of kisspeptin neurons of the arcuate nucleus (ARC) while simultaneously restraining POMC neuron number...
June 6, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29883730/culture-of-human-neurospheres-in-3d-scaffolds-for-developmental-neurotoxicity-testing
#4
Christine Hellwig, Marta Barenys, Jenny Baumann, Kathrin Gassmann, Laura Casanellas, Gerhard Kauer, Ellen Fritsche
Human neural progenitor cells cultured as neurospheres are a promising tool for developmental neurotoxicity testing in vitro. In order to obtain a human cell-based tissue culture system as close to the organ as possible, it is desirable to improve the spatial organization of the "Neurosphere Assay" and use 3D scaffolds to better mimic the in vivo three dimensional cell microenvironment. For this reason we have established the conditions for short-term culture (up to 6 days) in matrigel or in IKVAV-3 peptide-functionalized hydrogels, and for long-term culture (>25 days) in IKVAV-3 peptide-functionalized hydrogels showing that these conditions support human neural progenitor cells' migration, differentiation to neurons and formation of neuronal networks...
June 5, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29880921/mouse-medulloblastoma-driven-by-crispr-activation-of-cellular-myc
#5
BaoHan T Vo, Jin Ah Kwon, Chunliang Li, David Finkelstein, Beisi Xu, Brent A Orr, Charles J Sherr, Martine F Roussel
MYC-driven Group 3 (G3) medulloblastoma (MB) is the most aggressive of four molecular subgroups classified by transcriptome, genomic landscape and clinical outcomes. Mouse models that recapitulate human G3 MB all rely on retroviral vector-induced Myc expression driven by viral regulatory elements (Retro-Myc tumors). We used nuclease-deficient CRISPR/dCas9-based gene activation with combinatorial single guide RNAs (sgRNAs) to enforce transcription of endogenous Myc in Trp53-null neurospheres that were orthotopically transplanted into the brains of naïve animals...
June 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29871513/sequential-combined-treatment-of-pifithrin-%C3%AE-and-posiphen-enhances-neurogenesis-and-functional-recovery-after-stroke
#6
Flavia Turcato, Paul Kim, Austin Barnett, Yongming Jin, Mike Scerba, Anthony Casey, Warren Selman, Nigel H Greig, Yu Luo
OBJECTIVE: Although cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural stem cells (NSCs) in the subventricular zone (SVZ) and subgranular zone (SGZ), the majority of these new cells die shortly after injury and do not appropriately differentiate into neurons, or migrate and functionally integrate into the brain. The purpose of this study was to examine a novel strategy for treatment of stroke after injury by optimizing the survival of ischemia-induced endogenous NSCs in the SVZ and SGZ...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29867451/streptozotocin-impairs-proliferation-and-differentiation-of-adult-hippocampal-neural-stem-cells-in-vitro-correlation-with-alterations-in-the-expression-of-proteins-associated-with-the-insulin-system
#7
Ping Sun, Gabriela Ortega, Yan Tan, Qian Hua, Peter F Riederer, Jürgen Deckert, Angelika G Schmitt-Böhrer
Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29849044/defined-geldrop-cultures-maintain-neural-precursor-cells
#8
Steffen Vogler, Silvana Prokoph, Uwe Freudenberg, Marcus Binner, Mikhail Tsurkan, Carsten Werner, Gerd Kempermann
Distinct micro-environmental properties have been reported to be essential for maintenance of neural precursor cells (NPCs) within the adult brain. Due to high complexity and technical limitations, the natural niche can barely be studied systematically in vivo. By reconstituting selected environmental properties (adhesiveness, proteolytic degradability, and elasticity) in geldrop cultures, we show that NPCs can be maintained stably at high density over an extended period of time (up to 8 days). In both conventional systems, neurospheres and monolayer cultures, they would expand and (in the case of neurospheres) differentiate rapidly...
May 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29803091/crizotinib-and-erlotinib-inhibits-growth-of-c-met-egfrviii-primary-human-glioblastoma-xenografts
#9
C Rory Goodwin, Prakash Rath, Olutobi Oyinlade, Hernando Lopez, Salman Mughal, Shuli Xia, Yunqing Li, Harsharan Kaur, Xin Zhou, A Karim Ahmed, Sandra Ho, Alessandro Olivi, Bachchu Lal
OBJECTIVES: Receptor tyrosine kinases (RTK), such as c-Met and epidermal growth factor receptor (EGFR), are implicated in the malignant progression of glioblastoma. Studies show that RTK systems can co-modulate distinct and overlapping oncogenic downstream signaling pathways. EGFRvIII, a constitutively activated EGFR deletion mutant variant, leads to increased tumor growth and diminishes the tumor growth response to HGF: c-Met pathway inhibitor therapy. Conversely, activation of the c-Met pathway diminishes the tumor growth response to EGFR pathway inhibitors...
March 9, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29786763/mir-124-promotes-proliferation-and-neural-differentiation-of-neural-stem-cells-through-targeting-dact1-and-activating-wnt-%C3%AE-catenin-pathways
#10
Shujie Jiao, Yaling Liu, Yaobing Yao, Junfang Teng
Neural stem cells (NSCs) are multipotent and undifferentiated cells with the potential to differentiate into neuronal lineages and gliocytes. NSCs have the ability to generate and regenerate the brain, indicating the possibility of cell-based therapies for neurological disorders. miR-124 has been demonstrated as a modulator in the survival, expansion, and differentiation of NSCs. However, the underlying molecular mechanisms of miR-124 in NSC development are still far from being understood. The expressions of miR-124, dishevelled binding antagonist of beta-catenin 1 (DACT1), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), β-catenin, cyclinD1, and glycogen synthase kinase-3β (GSK-3β) were examined by qRT-PCR or western blot...
May 21, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29768530/ns1-codon-usage-adaptation-to-humans-in-pandemic-zika-virus
#11
Caio César de Melo Freire, Giuseppe Palmisano, Carla T Braconi, Fernanda R Cugola, Fabiele B Russo, Patricia Cb Beltrão-Braga, Atila Iamarino, Daniel Ferreira de Lima Neto, Amadou Alpha Sall, Livia Rosa-Fernandes, Martin R Larsen, Paolo Marinho de Andrade Zanotto
BACKGROUND: Zika virus (ZIKV) was recognised as a zoonotic pathogen in Africa and southeastern Asia. Human infections were infrequently reported until 2007, when the first known epidemic occurred in Micronesia. After 2013, the Asian lineage of ZIKV spread along the Pacific Islands and Americas, causing severe outbreaks with millions of human infections. The recent human infections of ZIKV were also associated with severe complications, such as an increase in cases of Guillain-Barre syndrome and the emergence of congenital Zika syndrome...
May 10, 2018: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29750582/a-cytotoxic-three-dimensional-spheroid-high-throughput-assay-using-patient-derived-glioma-stem-cells
#12
Victor Quereda, Shurong Hou, Franck Madoux, Louis Scampavia, Timothy P Spicer, Derek Duckett
Glioblastoma (GBM) is the most aggressive primary brain cancer with an average survival time after diagnosis of only 12-14 months, with few (<5%) long-term survivors. A growing body of work suggests that GBMs contain a small population of glioma stem cells (GSCs) that are thought to be major contributors to treatment resistance and disease relapse. Identifying compounds that modulate GSC proliferation would provide highly valuable molecular probes of GSC-directed signaling. However, targeting GSCs pharmacologically has been challenging...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29749381/effect-of-bmi1-over-expression-on-gene-expression-in-adult-and-embryonic-murine-neural-stem-cells
#13
Mythily Ganapathi, Nathan C Boles, Carol Charniga, Steven Lotz, Melissa Campbell, Sally Temple, Randall H Morse
The ability of isolated neural stem cells (NSCs) to proliferate as neurospheres is indicative of their competence as stem cells, and depends critically on the polycomb group (PcG) member Bmi1: knockdown of Bmi1 results in defective proliferation and self-renewal of isolated NSCs, whereas overexpression of Bmi1 enhances these properties. Here we report genome-wide changes in gene expression in embryonic and adult NSCs (eNSCs and aNSCs) caused by overexpression of Bmi1. We find that genes whose expression is altered by perturbations in Bmi1 levels in NSCs are mostly distinct from those affected in other multipotent stem/progenitor cells, such as those from liver and lung, aside from a small core of common targets that is enriched for genes associated with cell migration and mobility...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740281/heparan-sulfate-proteoglycans-as-drivers-of-neural-progenitors-derived-from-human-mesenchymal-stem-cells
#14
Rachel K Okolicsanyi, Lotta E Oikari, Chieh Yu, Lyn R Griffiths, Larisa M Haupt
Background: Due to their relative ease of isolation and their high ex vivo and in vitro expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation. Methods: Following the determination that hMSCs maintain neural potential throughout extended in vitro expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29737636/a-peroxiredoxin-based-proteinaceous-scaffold-for-the-growth-and-differentiation-of-neuronal-cells-and-tumour-stem-cells-in-the-absence-of-prodifferentiation-agents
#15
Annamaria Cimini, Matteo Ardini, Roberta Gentile, Francesco Giansanti, Elisabetta Benedetti, Loredana Cristiano, Alessia Fidoamore, Stefano Scotti, Gloria Panella, Francesco Angelucci, Rodolfo Ippoliti
The use of nanoscale materials in the design of scaffolds for CNS tissue is increasing, due to their ability to promote cell adhesion, to mimic an extracellular matrix microenvironment and to interact with neuronal membranes. In this framework, one of the major challenges when using undifferentiated neural cells is how to control the differentiation process. Here we report the characterization of a scaffold based on the self-assembled nanotubes of a mutant of the protein peroxiredoxin (from Schistosoma mansoni or Bos taurus), which allows the growth and differentiation of a model neuronal cell line (SHSY5Y)...
September 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29726088/a-novel-2-phenylamino-quinazoline-based-compound-expands-the-neural-stem-cell-pool-and-promotes-the-hippocampal-neurogenesis-and-the-cognitive-ability-of-adult-mice
#16
Lu Hui, Cheng Gang, Hong Feng, Zhang Lei, Hu Youhong, Feng Linyin
The adult neurogenesis occurs throughout the life of the mammalian hippocampus and is found to be essential for learning and memory. Identifying new ways to manipulate the number of neural stem cells (NSCs) and enhance endogenous neurogenesis in adult is very important. Here we found that a novel compound, N2-(4-isopropylphenyl)-5-(3-methoxyphenoxy)quinazoline-2,4-diamine (code-named Yhhu-3792), enhanced the self-renewal capability of NSCs in vitro and in vivo. In vitro, Yhhu-3792 increased the ratio of BrdU + /DAPI+ embryonic NSCs and accelerated the growth of neurospheres significantly...
May 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29721785/prodigiosin-stimulates-endoplasmic-reticulum-stress-and-induces-autophagic-cell-death-in-glioblastoma-cells
#17
Shu-Yu Cheng, Nan-Fu Chen, Hsiao-Mei Kuo, San-Nan Yang, Chun-Sung Sung, Ping-Jyun Sung, Zhi-Hong Wen, Wu-Fu Chen
Prodigiosin, a secondary metabolite isolated from marine Vibrio sp., has antimicrobial and anticancer properties. This study investigated the cell death mechanism of prodigiosin in glioblastoma. Glioblastoma multiforme (GBM) is an aggressive primary cancer of the central nervous system. Despite treatment, or standard therapy, the median survival of glioblastoma patients is about 14.6 month. The results of the present study clearly showed that prodigiosin significantly reduced the cell viability and neurosphere formation ability of U87MG and GBM8401 human glioblastoma cell lines...
May 2, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29718345/pi3k-activation-in-neural-stem-cells-drives-tumorigenesis-which-can-be-ameliorated-by-targeting-the-camp-response-element-binding-creb-protein
#18
Paul M Daniel, Gulay Filiz, Daniel V Brown, Michael Christie, Paul M Waring, Yi Zhang, John M Haynes, Colin Pouton, Dustin Flanagan, Elizabeth Vincan, Terrance G Johns, Karen Montgomery, Wayne A Phillips, Theo Mantamadiotis
Background: Hyperactivation of PI3K signaling is common in cancers but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells, where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. Methods: To investigate the role for the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, PTEN, to neural stem/progenitor cells (NSPCs)...
April 30, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29715082/efficacy-of-asparaginase-erwinia-chrysanthemi-with-and-without-temozolomide-against-glioma-cells-and-intracranial-mouse-medulloblastoma
#19
Valentina Sanghez, Mengqing Chen, Shan Li, Tsui-Fen Chou, Michelina Iacovino, Henry J Lin, Joseph L Lasky, Eduard H Panosyan
BACKGROUND: Anti-metabolites are less-myelosuppressive than DNA-damaging anticancer drugs and may be useful against brain tumors. MATERIALS AND METHODS: We evaluated the asparagine/glutamine-deaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. RESULTS: Erwinaze treatment of cell lines and neurospheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC50 s) of 0...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29706656/the-constitutive-activity-of-the-virally-encoded-chemokine-receptor-us28-accelerates-glioblastoma-growth
#20
Raimond Heukers, Tian Shu Fan, Raymond H de Wit, Jeffrey R van Senten, Timo W M De Groof, Maarten P Bebelman, Tonny Lagerweij, Joao Vieira, Sabrina M de Munnik, Laura Smits-de Vries, Jody van Offenbeek, Afsar Rahbar, Diane van Hoorick, Cecilia Söderberg-Naucler, Thomas Würdinger, Rob Leurs, Marco Siderius, Henry F Vischer, Martine J Smit
Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA and encoded proteins, including the chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity and is able to bind several human chemokines, leading to the activation of various proliferative and inflammatory signaling pathways. Here we show that HCMV, through the expression of US28, significantly enhanced the growth of 3D spheroids of U251- and neurospheres of primary glioblastoma cells...
April 30, 2018: Oncogene
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