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40
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Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1093/hmg/ddw322" target="_blank" rel="noreferrer noopener">http://doi.org/10.1093/hmg/ddw322</a>
Pages
5126–5141
Issue
23
Volume
25
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice.
Publisher
An entity responsible for making the resource available
Human molecular genetics
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-12
Subject
The topic of the resource
Animal; Animals; Calcium Signaling/genetics; Dantrolene/*administration & dosage; Disease Models; Gaucher Disease/*drug therapy/genetics/physiopathology; Humans; Mice; Mitochondria/*drug effects/genetics/pathology; Neurons/drug effects/pathology; Neuroprotective Agents/administration & dosage; Ryanodine Receptor Calcium Release Channel/*genetics/metabolism
Creator
An entity primarily responsible for making the resource
Liou Benjamin; Peng Yanyan; Li Ronghua; Inskeep Venette; Zhang Wujuan; Quinn Brian; Dasgupta Nupur; Blackwood Rachel; Setchell Kenneth D R; Fleming Sheila; Grabowski Gregory A; Marshall John; Sun Ying
Description
An account of the resource
Neuronopathic Gaucher disease (nGD) manifests as severe neurological symptoms in patients with no effective treatment available. Ryanodine receptors (Ryrs) are a family of calcium release channels on intracellular stores. The goal of this study is to determine if Ryrs are potential targets for nGD treatment. A nGD cell model (CBE-N2a) was created by inhibiting acid beta-glucosidase (GCase) in N2a cells with conduritol B epoxide (CBE). Enhanced cytosolic calcium in CBE-N2a cells was blocked by either ryanodine or dantrolene, antagonists of Ryrs and by Genz-161, a glucosylceramide synthase inhibitor, suggesting substrate-mediated
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1093/hmg/ddw322" target="_blank" rel="noreferrer noopener">10.1093/hmg/ddw322</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2016
Animal
Animals
Blackwood Rachel
Calcium Signaling/genetics
Dantrolene/*administration & dosage
Dasgupta Nupur
Department of Pharmaceutical Sciences
Disease Models
Fleming Sheila
Gaucher Disease/*drug therapy/genetics/physiopathology
Grabowski Gregory A
Human molecular genetics
Humans
Inskeep Venette
Li Ronghua
Liou Benjamin
Marshall John
Mice
Mitochondria/*drug effects/genetics/pathology
NEOMED College of Pharmacy
Neurons/drug effects/pathology
Neuroprotective Agents/administration & dosage
Peng Yanyan
Quinn Brian
Ryanodine Receptor Calcium Release Channel/*genetics/metabolism
Setchell Kenneth D R
Sun Ying
Zhang Wujuan
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1038/onc.2015.83" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/onc.2015.83</a>
Pages
314–322
Issue
3
Volume
35
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Activation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and improves cancer therapy.
Publisher
An entity responsible for making the resource available
Oncogene
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-01
Subject
The topic of the resource
Animals; Calcium Signaling/genetics; Carcinoma; Cell Line; Cell Proliferation/drug effects; Cisplatin/administration & dosage; Endothelium; Gene Expression Regulation; Humans; Leucine/administration & dosage/analogs & derivatives; Lewis Lung/drug therapy/*genetics/pathology; Mice; Neoplastic/drug effects; Neovascularization; Pathologic/drug therapy/*genetics/pathology; Sulfonamides/administration & dosage; TRPV Cation Channels/agonists/biosynthesis/*genetics; Tumor; Vascular Endothelial Growth Factor A/genetics; Vascular/drug effects/*pathology
Creator
An entity primarily responsible for making the resource
Adapala R K; Thoppil R J; Ghosh K; Cappelli H C; Dudley A C; Paruchuri S; Keshamouni V; Klagsbrun M; Meszaros J G; Chilian W M; Ingber D E; Thodeti C K
Description
An account of the resource
Tumor vessels are characterized by abnormal morphology and hyperpermeability that together cause inefficient delivery of chemotherapeutic agents. Although vascular endothelial growth factor has been established as a critical regulator of tumor angiogenesis, the role of mechanical signaling in the regulation of tumor vasculature or tumor endothelial cell (TEC) function is not known. Here we show that the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) regulates tumor angiogenesis and tumor vessel maturation via modulation of TEC mechanosensitivity. We found that TECs exhibit reduced TRPV4 expression and function, which is correlated with aberrant mechanosensitivity towards extracellular matrix stiffness, increased migration and abnormal angiogenesis by TEC. Further, syngeneic tumor experiments revealed that the absence of TRPV4 induced increased vascular density, vessel diameter and reduced pericyte coverage resulting in enhanced tumor growth in TRPV4 knockout mice. Importantly, overexpression or pharmacological activation of TRPV4 restored aberrant TEC mechanosensitivity, migration and normalized abnormal angiogenesis in vitro by modulating Rho activity. Finally, a small molecule activator of TRPV4, GSK1016790A, in combination with anticancer drug cisplatin, significantly reduced tumor growth in wild-type mice by inducing vessel maturation. Our findings demonstrate TRPV4 channels to be critical regulators of tumor angiogenesis and represent a novel target for anti-angiogenic and vascular normalization therapies.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1038/onc.2015.83" target="_blank" rel="noreferrer noopener">10.1038/onc.2015.83</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2016
Adapala R K
Animals
Calcium Signaling/genetics
Cappelli H C
Carcinoma
Cell Line
Cell Proliferation/drug effects
Chilian W M
Cisplatin/administration & dosage
Department of Integrative Medical Sciences
Dudley A C
Endothelium
Gene Expression Regulation
Ghosh K
Humans
Ingber D E
Keshamouni V
Klagsbrun M
Leucine/administration & dosage/analogs & derivatives
Lewis Lung/drug therapy/*genetics/pathology
Meszaros J G
Mice
NEOMED College of Medicine
Neoplastic/drug effects
Neovascularization
Oncogene
Paruchuri S
Pathologic/drug therapy/*genetics/pathology
Sulfonamides/administration & dosage
Thodeti C K
Thoppil R J
TRPV Cation Channels/agonists/biosynthesis/*genetics
Tumor
Vascular Endothelial Growth Factor A/genetics
Vascular/drug effects/*pathology