Bioeffects of ultrasound-stimulated microbubbles on endothelial cells: gene expression changes associated with radiation enhancement in vitro. 2012

Azza A Al-Mahrouki, and Raffi Karshafian, and Anoja Giles, and Gregory J Czarnota
Radiation Oncology and Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Ultrasound can be used to target endothelial cells in cancer therapy where the destruction of vasculature leads to tumor cell death. Here, we demonstrate ultrasound bioeffects in which the levels of genes in endothelial cells can be significantly altered by ultrasound-stimulated microbubble exposure. These were compared with established effects of radiation on endothelial cells at a gene level. Human-endothelial cells were exposed to ultrasound and microbubbles, radiation or combinations of ultrasound, microbubbles and radiation. Gene expression analyses revealed an up-regulation of genes known to be involved in apoptosis and ceramide-induced apoptotic pathways, including SMPD2, UGT8, COX6B1, Caspase 9 and MAP2K1 with ultrasound-stimulated microbubble exposure but not SMPD1. This was supported by immunohistochemistry and morphologic changes examined with cell microscopy, which showed changes in SMPD1 gene product in cells with microbubble exposure. This supports the hypothesis that ultrasound-stimulated microbubbles can induce significant bioeffect-related changes in gene expression and can affect ceramide signaling pathways in endothelial cells, leading to apoptosis.

UI MeSH Term Description Entries
D011829 Radiation Dosage The amount of radiation energy that is deposited in a unit mass of material, such as tissues of plants or animal. In RADIOTHERAPY, radiation dosage is expressed in gray units (Gy). In RADIOLOGIC HEALTH, the dosage is expressed by the product of absorbed dose (Gy) and quality factor (a function of linear energy transfer), and is called radiation dose equivalent in sievert units (Sv). Sievert Units,Dosage, Radiation,Gray Units,Gy Radiation,Sv Radiation Dose Equivalent,Dosages, Radiation,Radiation Dosages,Units, Gray,Units, Sievert
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D005466 Fluorocarbons Liquid perfluorinated carbon compounds which may or may not contain a hetero atom such as nitrogen, oxygen or sulfur, but do not contain another halogen or hydrogen atom. This concept includes fluorocarbon emulsions, and fluorocarbon blood substitutes. Perfluorinated and related polyfluorinated chemicals are referred to as PFAS and are defined as chemicals with at least two adjacent carbon atoms, where one carbon is fully fluorinated and the other is at least partially fluorinated. Fluorocarbon,Fluorocarbon Emulsion,Fluorocarbon Emulsions,Fluorotelomer Phosphate Esters,N-Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per- and Polyfluoroalkyl Substances,PFC Perfluorinated Chemicals,PFECAs Perfluoropolyether Carboxylic Acids,Per- and Polyfluoroalkyl Substances,Perfluoroalkane Sulfonamides,Perfluoroalkyl Carboxylates,Perfluoroalkyl Ether Carboxylates,Perfluoroalkyl Polyether Carboxylates,Perfluorocarbon,Perfluorocarbons,Perfluoropolyether Carboxylic Acids,Polyfluorocarbons,Fluorinated Telomer Alcohols,Fluoro-Telomer Alcohols,Polyfluorinated Telomer Alcohols,Telomer Fluorocarbons,Acids, Perfluoropolyether Carboxylic,Alcohols, Fluorinated Telomer,Alcohols, Fluoro-Telomer,Alcohols, Polyfluorinated Telomer,Carboxylates, Perfluoroalkyl,Carboxylates, Perfluoroalkyl Ether,Carboxylates, Perfluoroalkyl Polyether,Carboxylic Acids, Perfluoropolyether,Chemicals, PFC Perfluorinated,Emulsion, Fluorocarbon,Emulsions, Fluorocarbon,Esters, Fluorotelomer Phosphate,Ether Carboxylates, Perfluoroalkyl,Fluoro Telomer Alcohols,Fluorocarbons, Telomer,N Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per and Polyfluoroalkyl Substances,Per and Polyfluoroalkyl Substances,Perfluorinated Chemicals, PFC,Phosphate Esters, Fluorotelomer,Polyether Carboxylates, Perfluoroalkyl,Sulfonamides, Perfluoroalkane,Telomer Alcohols, Fluorinated,Telomer Alcohols, Polyfluorinated
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013010 Sonication The application of high intensity ultrasound to liquids. Sonications
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D045423 Microbubbles Small encapsulated gas bubbles (diameters of micrometers) that can be used as CONTRAST MEDIA, and in other diagnostic and therapeutic applications. Upon exposure to sufficiently intense ultrasound, microbubbles will cavitate, rupture, disappear, release gas content. Such characteristics of the microbubbles can be used to enhance diagnostic tests, dissolve blood clots, and deliver drugs or genes for therapy. Colloidal Gas Aphrons,Aphron, Colloidal Gas,Aphrons, Colloidal Gas,Colloidal Gas Aphron,Gas Aphron, Colloidal,Gas Aphrons, Colloidal,Microbubble
D019220 High-Energy Shock Waves High-amplitude compression waves, across which density, pressure, and particle velocity change drastically. The mechanical force from these shock waves can be used for mechanically disrupting tissues and deposits. HESW,Shock Waves, High-Energy,Shockwaves, Ultrasonic,High Energy Shock Waves,Shock Waves, Ultrasonic,High-Energy Shock Wave,Shock Wave, High-Energy,Shock Wave, Ultrasonic,Shock Waves, High Energy,Shockwave, Ultrasonic,Ultrasonic Shock Wave,Ultrasonic Shock Waves,Ultrasonic Shockwave,Ultrasonic Shockwaves,Wave, High-Energy Shock,Wave, Ultrasonic Shock,Waves, High-Energy Shock,Waves, Ultrasonic Shock

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