LIVIVO - Search results -

Search results

Result 1 - 10 of total 20

Search options

Article ; Online: Engineered In Vitro Tumor Model Recapitulates Molecular Signatures of Invasion in Glioblastoma.

Smith, Laura J / Skirzynska, Arianna / Chin, Allysia A / Arnold, Amy E / Kushida, Michelle / Dirks, Peter B / Shoichet, Molly S

ACS materials Au

2023 Volume 3, Issue 5, Page(s) 514–527

Abstract: Glioblastoma stem cells (GSCs) play an important role in the invasive nature of glioblastoma (GBM); yet, the mechanisms driving this behavior are poorly understood. To recapitulate tumor invasion in vitro, we developed a GBM tumor-mimetic hydrogel using ... ...

Abstract	Glioblastoma stem cells (GSCs) play an important role in the invasive nature of glioblastoma (GBM); yet, the mechanisms driving this behavior are poorly understood. To recapitulate tumor invasion in vitro, we developed a GBM tumor-mimetic hydrogel using extracellular matrix components upregulated in patients. We show that our hydrogel facilitates the infiltration of a subset of patient-derived GSCs, differentiating samples based on phenotypic invasion. Invasive GSCs are enriched for injury-responsive pathways while noninvasive GSCs are enriched for developmental pathways, reflecting established GSC stratifications. Using small molecule inhibitors, we demonstrate that the suppression of matrix metalloprotease and rho-associated protein kinase processes results in a significant reduction of cell invasion into the hydrogel, reflecting mesenchymal- and amoeboid-dependent mechanisms. Similar reduction in cell invasion was observed by siRNA knockdown of ITGB1 and FAK focal adhesion pathways. We elucidate the transcriptomic profile of cells invading in the hydrogel by performing bulk RNA sequencing of cells cultured in the hydrogel and compare these to cells cultured in conventional tissue culture polystyrene (TCP). In our 3D hydrogel cultures, invasion-related molecular signatures along with proliferation and injury response pathways are upregulated while development processes are downregulated compared to culture on 2D TCP. With this validated in vitro model, we establish a valuable tool to find therapeutic intervention strategies against cellular invasion in glioblastoma.
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Journal Article
ISSN	2694-2461
ISSN (online)	2694-2461
DOI	10.1021/acsmaterialsau.3c00029
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Medulloblastoma Arises from the Persistence of a Rare and Transient Sox2

Selvadurai, Hayden J / Luis, Erika / Desai, Kinjal / Lan, Xiaoyang / Vladoiu, Maria C / Whitley, Owen / Galvin, Ciaran / Vanner, Robert J / Lee, Lilian / Whetstone, Heather / Kushida, Michelle / Nowakowski, Tomasz / Diamandis, Phedias / Hawkins, Cynthia / Bader, Gary / Kriegstein, Arnold / Taylor, Michael D / Dirks, Peter B

Cell reports

2020 Volume 31, Issue 2, Page(s) 107511

Abstract: Medulloblastoma (MB) is a neoplasm linked to dysregulated cerebellar development. Previously, we demonstrated that the Sonic Hedgehog (SHH) subgroup grows hierarchically, with ... ...

Abstract	Medulloblastoma (MB) is a neoplasm linked to dysregulated cerebellar development. Previously, we demonstrated that the Sonic Hedgehog (SHH) subgroup grows hierarchically, with Sox2
MeSH term(s)	Animals ; Cell Lineage/genetics ; Cells, Cultured ; Cerebellar Neoplasms/pathology ; Cerebellum/embryology ; Female ; Hedgehog Proteins/metabolism ; Humans ; Male ; Medulloblastoma/etiology ; Medulloblastoma/metabolism ; Mice, Knockout ; Mice, Transgenic ; Neoplasm Recurrence, Local/pathology ; Neural Stem Cells/metabolism ; Neurogenesis ; Neurons/metabolism ; SOXB1 Transcription Factors/metabolism ; SOXB1 Transcription Factors/physiology ; Signal Transduction/physiology ; Single-Cell Analysis/methods
Chemical Substances	Hedgehog Proteins ; SOX2 protein, human ; SOXB1 Transcription Factors
Language	English
Publishing date	2020-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.03.075
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.

MacLeod, Graham / Bozek, Danielle A / Rajakulendran, Nishani / Monteiro, Vernon / Ahmadi, Moloud / Steinhart, Zachary / Kushida, Michelle M / Yu, Helen / Coutinho, Fiona J / Cavalli, Florence M G / Restall, Ian / Hao, Xiaoguang / Hart, Traver / Luchman, H Artee / Weiss, Samuel / Dirks, Peter B / Angers, Stephane

Cell reports

2019 Volume 27, Issue 3, Page(s) 971–986.e9

Abstract: Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding ... ...

Abstract	Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.
MeSH term(s)	Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/mortality ; Brain Neoplasms/pathology ; CRISPR-Cas Systems/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/genetics ; Endopeptidases/genetics ; Endopeptidases/metabolism ; Endosomal Sorting Complexes Required for Transport/genetics ; Endosomal Sorting Complexes Required for Transport/metabolism ; Female ; Gene Editing/methods ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Library ; Glioblastoma/drug therapy ; Glioblastoma/mortality ; Glioblastoma/pathology ; Histone Methyltransferases/metabolism ; Humans ; Mice ; Mice, SCID ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Suppressor of Cytokine Signaling 3 Protein/genetics ; Suppressor of Cytokine Signaling 3 Protein/metabolism ; Survival Analysis ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	Endosomal Sorting Complexes Required for Transport ; SOCS3 protein, human ; Suppressor of Cytokine Signaling 3 Protein ; Histone Methyltransferases (EC 2.1.1.-) ; Endopeptidases (EC 3.4.-) ; USP8 protein, human (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2019-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.03.047
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and formation of tracheal cartilage.

Park, Jinhyung / Zhang, Jennifer J R / Moro, Anne / Kushida, Michelle / Wegner, Michael / Kim, Peter C W

Developmental dynamics : an official publication of the American Association of Anatomists

2010 Volume 239, Issue 2, Page(s) 514–526

Abstract: We report that Sonic Hedgehog (Shh) regulates both formation and patterning of tracheal cartilage by controlling the expression pattern and level of the chondrogenic gene, Sox9. In Shh(-/-) tracheo-esophageal tubes, Sox9 expression is transient and not ... ...

Abstract	We report that Sonic Hedgehog (Shh) regulates both formation and patterning of tracheal cartilage by controlling the expression pattern and level of the chondrogenic gene, Sox9. In Shh(-/-) tracheo-esophageal tubes, Sox9 expression is transient and not restricted ventrally to the site of chondrogenesis, and is absent at the time of chondrogenesis, resulting in the failure of tracheal cartilage formation. Inhibition of Hedgehog signalling with cyclopamine in tracheal cultures prevents tracheal cartilage formation, while treatment of Shh(-/-) tracheal explant with exogenous Shh peptide rescues cartilage formation. Both exogenous Bmp4 and Noggin rescue cartilage phenotype in Shh(-/-) tracheal culture, while promoting excessive cartilage development in wild-type trachea through induction of Sox9 expression. The ventral and segmented expression of Sox9 in tracheal primordia under Shh modulated by Bmp4 and Noggin thus determine where and when tracheal cartilage develops. These results indicate that Shh signalling is a critical determinant in tracheal cartilage development.
MeSH term(s)	Animals ; Apoptosis ; Bone Morphogenetic Protein 4/metabolism ; Carrier Proteins/metabolism ; Cell Proliferation ; Chondrogenesis ; Gene Expression Regulation, Developmental ; Hedgehog Proteins/metabolism ; Kruppel-Like Transcription Factors/metabolism ; Laryngeal Cartilages/embryology ; Mice ; Mice, Knockout ; SOX9 Transcription Factor/metabolism ; Zinc Finger Protein GLI1
Chemical Substances	Bmp4 protein, mouse ; Bone Morphogenetic Protein 4 ; Carrier Proteins ; Gli protein, mouse ; Hedgehog Proteins ; Kruppel-Like Transcription Factors ; SOX9 Transcription Factor ; Shh protein, mouse ; Sox9 protein, mouse ; Zinc Finger Protein GLI1 ; noggin protein (148294-77-3)
Language	English
Publishing date	2010-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.22192
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ub I Zs.60: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 64: Show issues

Order via subito

Details ▾

Article ; Online: Single-cell chromatin accessibility profiling of glioblastoma identifies an invasive cancer stem cell population associated with lower survival.

Guilhamon, Paul / Chesnelong, Charles / Kushida, Michelle M / Nikolic, Ana / Singhal, Divya / MacLeod, Graham / Madani Tonekaboni, Seyed Ali / Cavalli, Florence Mg / Arlidge, Christopher / Rajakulendran, Nishani / Rastegar, Naghmeh / Hao, Xiaoguang / Hassam, Rozina / Smith, Laura J / Whetstone, Heather / Coutinho, Fiona J / Nadorp, Bettina / Ellestad, Katrina I / Luchman, H Artee /

Chan, Jennifer Ai-Wen / Shoichet, Molly S / Taylor, Michael D / Haibe-Kains, Benjamin / Weiss, Samuel / Angers, Stephane / Gallo, Marco / Dirks, Peter B / Lupien, Mathieu

eLife

2021 Volume 10

Abstract: Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime ... ...

Abstract	Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary human GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In-depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival, in line with the higher invasive properties of Invasive state GSCs compared to Reactive and Constructive GSCs as shown by in vitro and in vivo assays. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.
MeSH term(s)	Cell Line, Tumor ; Cell Self Renewal ; Chromatin/metabolism ; Female ; Glioblastoma/secondary ; Humans ; Male ; Neoplastic Stem Cells/physiology ; Single-Cell Analysis
Chemical Substances	Chromatin
Language	English
Publishing date	2021-01-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.64090
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer.

Wu, Qin / Ba-Alawi, Wail / Deblois, Genevieve / Cruickshank, Jennifer / Duan, Shili / Lima-Fernandes, Evelyne / Haight, Jillian / Tonekaboni, Seyed Ali Madani / Fortier, Anne-Marie / Kuasne, Hellen / McKee, Trevor D / Mahmoud, Hassan / Kushida, Michelle / Cameron, Sarina / Dogan-Artun, Nergiz / Chen, WenJun / Nie, Yan / Zhang, Lan Xin / Vellanki, Ravi N /

Zhou, Stanley / Prinos, Panagiotis / Wouters, Bradly G / Dirks, Peter B / Done, Susan J / Park, Morag / Cescon, David W / Haibe-Kains, Benjamin / Lupien, Mathieu / Arrowsmith, Cheryl H

Nature communications

2020 Volume 11, Issue 1, Page(s) 4205

Abstract: Triple negative breast cancer (TNBC) is a deadly form of breast cancer due to the development of resistance to chemotherapy affecting over 30% of patients. New therapeutics and companion biomarkers are urgently needed. Recognizing the elevated expression ...

Abstract	Triple negative breast cancer (TNBC) is a deadly form of breast cancer due to the development of resistance to chemotherapy affecting over 30% of patients. New therapeutics and companion biomarkers are urgently needed. Recognizing the elevated expression of glucose transporter 1 (GLUT1, encoded by SLC2A1) and associated metabolic dependencies in TNBC, we investigated the vulnerability of TNBC cell lines and patient-derived samples to GLUT1 inhibition. We report that genetic or pharmacological inhibition of GLUT1 with BAY-876 impairs the growth of a subset of TNBC cells displaying high glycolytic and lower oxidative phosphorylation (OXPHOS) rates. Pathway enrichment analysis of gene expression data suggests that the functionality of the E2F pathway may reflect to some extent OXPHOS activity. Furthermore, the protein levels of retinoblastoma tumor suppressor (RB1) strongly correlate with the degree of sensitivity to GLUT1 inhibition in TNBC, where RB1-negative cells are insensitive to GLUT1 inhibition. Collectively, our results highlight a strong and targetable RB1-GLUT1 metabolic axis in TNBC and warrant clinical evaluation of GLUT1 inhibition in TNBC patients stratified according to RB1 protein expression levels.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Biomarkers, Tumor ; Breast Neoplasms/metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Glucose Transporter Type 1/antagonists & inhibitors ; Glucose Transporter Type 1/genetics ; Glucose Transporter Type 1/metabolism ; Humans ; Mice ; Oxidative Phosphorylation ; Proteomics ; Pyrazoles/pharmacology ; Pyridines/pharmacology ; Quinolines ; RNA, Messenger/metabolism ; Retinoblastoma Binding Proteins/metabolism ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	BAY-876 ; Biomarkers, Tumor ; Glucose Transporter Type 1 ; Pyrazoles ; Pyridines ; Quinolines ; RB1 protein, human ; RNA, Messenger ; Retinoblastoma Binding Proteins ; SLC2A1 protein, human ; STF-31 ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2020-08-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-18020-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression.

Neuron

2018 Volume 100, Issue 4, Page(s) 799–815.e7

Abstract: Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that mechanosensitive ion channel Piezo regulates mitosis and ... ...

Abstract	Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival. Focal mechanical force activates prominent PIEZO1-dependent currents from glioma cell processes, but not soma. PIEZO1 localizes at focal adhesions to activate integrin-FAK signaling, regulate extracellular matrix, and reinforce tissue stiffening. In turn, a stiffer mechanical microenvironment elevates PIEZO1 expression to promote glioma aggression. Therefore, glioma cells are mechanosensory in a PIEZO1-dependent manner, and targeting PIEZO1 represents a strategy to break the reciprocal, disease-aggravating feedforward circuit between tumor cell mechanotransduction and the aberrant tissue mechanics. VIDEO ABSTRACT.
MeSH term(s)	Adult ; Aged ; Animals ; Animals, Genetically Modified ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Drosophila melanogaster ; Female ; Glioma/genetics ; Glioma/metabolism ; Glioma/pathology ; Humans ; Ion Channels/biosynthesis ; Ion Channels/genetics ; Male ; Mechanotransduction, Cellular/physiology ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Invasiveness/pathology ; Tumor Microenvironment/physiology ; Xenograft Model Antitumor Assays/methods
Chemical Substances	Ion Channels ; PIEZO1 protein, human
Language	English
Publishing date	2018-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2018.09.046
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

Order via subito

Details ▾

Article ; Online: Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma.

Faria, Claudia C / Agnihotri, Sameer / Mack, Stephen C / Golbourn, Brian J / Diaz, Roberto J / Olsen, Samantha / Bryant, Melissa / Bebenek, Matthew / Wang, Xin / Bertrand, Kelsey C / Kushida, Michelle / Head, Renee / Clark, Ian / Dirks, Peter / Smith, Christian A / Taylor, Michael D / Rutka, James T

Oncotarget

2015 Volume 6, Issue 25, Page(s) 21718–21729

Abstract: Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor ... ...

Abstract	Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.
MeSH term(s)	Acetophenones/chemistry ; Animals ; Antineoplastic Agents/chemistry ; Benzazepines/chemistry ; Benzopyrans/chemistry ; Brain Neoplasms/drug therapy ; Cell Line ; Cell Proliferation ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Dioxolanes/chemistry ; Drug Screening Assays, Antitumor ; Flunarizine/chemistry ; Gene Expression Profiling ; Genomics ; Humans ; Indoles/chemistry ; Medulloblastoma/drug therapy ; Mice ; Neoplasm Metastasis ; Neoplasm Transplantation ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; RNA/metabolism
Chemical Substances	Acetophenones ; Antineoplastic Agents ; Benzazepines ; Benzopyrans ; Dioxolanes ; Indoles ; MYC protein, human ; Proto-Oncogene Proteins c-myc ; alsterpaullone ; RNA (63231-63-0) ; rottlerin (E29LP3ZMUH) ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; piperlongumine (SGD66V4SVJ) ; Flunarizine (R7PLA2DM0J)
Language	English
Publishing date	2015-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.4304
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Sachamitr, Patty / Ho, Jolene C / Ciamponi, Felipe E / Ba-Alawi, Wail / Coutinho, Fiona J / Guilhamon, Paul / Kushida, Michelle M / Cavalli, Florence M G / Lee, Lilian / Rastegar, Naghmeh / Vu, Victoria / Sánchez-Osuna, María / Coulombe-Huntington, Jasmin / Kanshin, Evgeny / Whetstone, Heather / Durand, Mathieu / Thibault, Philippe / Hart, Kirsten / Mangos, Maria /

Veyhl, Joseph / Chen, Wenjun / Tran, Nhat / Duong, Bang-Chi / Aman, Ahmed M / Che, Xinghui / Lan, Xiaoyang / Whitley, Owen / Zaslaver, Olga / Barsyte-Lovejoy, Dalia / Richards, Laura M / Restall, Ian / Caudy, Amy / Röst, Hannes L / Bonday, Zahid Quyoom / Bernstein, Mark / Das, Sunit / Cusimano, Michael D / Spears, Julian / Bader, Gary D / Pugh, Trevor J / Tyers, Mike / Lupien, Mathieu / Haibe-Kains, Benjamin / Artee Luchman, H / Weiss, Samuel / Massirer, Katlin B / Prinos, Panagiotis / Arrowsmith, Cheryl H / Dirks, Peter B

Nature communications

2021 Volume 12, Issue 1, Page(s) 979

Abstract: Glioblastoma (GBM) is a deadly cancer in which cancer stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising target in GBM. Using two orthogonal- ... ...

Abstract	Glioblastoma (GBM) is a deadly cancer in which cancer stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising target in GBM. Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition of PRMT5 suppresses the growth of a cohort of 46 patient-derived GBM stem cell cultures, with the proneural subtype showing greater sensitivity. We show that PRMT5 inhibition causes widespread disruption of splicing across the transcriptome, particularly affecting cell cycle gene products. We identify a GBM splicing signature that correlates with the degree of response to PRMT5 inhibition. Importantly, we demonstrate that LLY-283 is brain-penetrant and significantly prolongs the survival of mice with orthotopic patient-derived xenografts. Collectively, our findings provide a rationale for the clinical development of brain penetrant PRMT5 inhibitors as treatment for GBM.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Apoptosis ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Discovery ; Epigenomics ; Female ; Gene Expression Regulation, Neoplastic ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Mice ; Neoplastic Stem Cells/metabolism ; Protein-Arginine N-Methyltransferases/drug effects ; Protein-Arginine N-Methyltransferases/genetics ; Protein-Arginine N-Methyltransferases/metabolism ; RNA Splicing ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; PRMT5 protein, human (EC 2.1.1.319) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319)
Language	English
Publishing date	2021-02-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-21204-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity.

Meyer, Mona / Reimand, Jüri / Lan, Xiaoyang / Head, Renee / Zhu, Xueming / Kushida, Michelle / Bayani, Jane / Pressey, Jessica C / Lionel, Anath C / Clarke, Ian D / Cusimano, Michael / Squire, Jeremy A / Scherer, Stephen W / Bernstein, Mark / Woodin, Melanie A / Bader, Gary D / Dirks, Peter B

Proceedings of the National Academy of Sciences of the United States of America

2015 Volume 112, Issue 3, Page(s) 851–856

Abstract: Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally ...

Abstract	Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Dacarbazine/analogs & derivatives ; Dacarbazine/therapeutic use ; Drug Resistance, Neoplasm ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/pathology ; Humans ; Single-Cell Analysis
Chemical Substances	Antineoplastic Agents ; Dacarbazine (7GR28W0FJI) ; temozolomide (YF1K15M17Y)
Language	English
Publishing date	2015-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1320611111
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito