Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice
The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer...
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Veröffentlicht in: | Journal of aerosol medicine 2013-06, Vol.26 (3), p.165-173 |
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creator | HWANG, Soon-Kyung CHANG, Seung-Hee MINAI-TEHRANI, Arash KIM, Yeon-Soo CHO, Myung-Haing |
description | The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer numerous advantages over invasive modes of delivery.
The potential effects of aerosol-delivered lentiviral-based short hairpin AIMP2 lacking exon 2 (shDX2) on lung tumorigenesis were studied. Lentiviral-based shDX2 was delivered into AIMP2(+/-) mice through a nose-only inhalation system twice a week for 4 weeks.
The effects of shDX2 on lung cancer progression and the Akt1-mTOR-p70S6K signaling pathway were evaluated. Long-term repeated delivery of lentiviral-based shDX2 suppressed lung tumor progression significantly by inhibiting Akt1-related signals and decreasing both protein synthesis and angiogenesis. In vivo, the aerosol-mediated application of lentiviral-based short hairpin RNAs was successful in achieving potent and specific knockdown of the target. The collective results indicate the therapeutic potential of the repeated delivery of shDX2 for lung cancer treatment and prevention. |
doi_str_mv | 10.1089/jamp.2011.0959 |
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The potential effects of aerosol-delivered lentiviral-based short hairpin AIMP2 lacking exon 2 (shDX2) on lung tumorigenesis were studied. Lentiviral-based shDX2 was delivered into AIMP2(+/-) mice through a nose-only inhalation system twice a week for 4 weeks.
The effects of shDX2 on lung cancer progression and the Akt1-mTOR-p70S6K signaling pathway were evaluated. Long-term repeated delivery of lentiviral-based shDX2 suppressed lung tumor progression significantly by inhibiting Akt1-related signals and decreasing both protein synthesis and angiogenesis. In vivo, the aerosol-mediated application of lentiviral-based short hairpin RNAs was successful in achieving potent and specific knockdown of the target. The collective results indicate the therapeutic potential of the repeated delivery of shDX2 for lung cancer treatment and prevention.</description><identifier>ISSN: 1941-2711</identifier><identifier>EISSN: 1941-2703</identifier><identifier>DOI: 10.1089/jamp.2011.0959</identifier><identifier>PMID: 23517169</identifier><language>eng</language><publisher>New Rochelle, NY: Mary Ann Liebert</publisher><subject>Administration, Inhalation ; Aerosols ; Amino Acyl-tRNA Synthetases - genetics ; Animals ; Biological and medical sciences ; Cell Proliferation ; Disease Progression ; Gene Knockdown Techniques ; Gene Transfer Techniques ; General pharmacology ; Lentivirus - genetics ; Lung - metabolism ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Medical sciences ; Mice ; Neovascularization, Pathologic - prevention & control ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Small Interfering - administration & dosage ; Signal Transduction</subject><ispartof>Journal of aerosol medicine, 2013-06, Vol.26 (3), p.165-173</ispartof><rights>2014 INIST-CNRS</rights><rights>(©) Copyright 2013, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-5067398d98b74cc313597246db2922053335d803462cdebb67d1687050ff41ff3</citedby><cites>FETCH-LOGICAL-c353t-5067398d98b74cc313597246db2922053335d803462cdebb67d1687050ff41ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27457966$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23517169$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HWANG, Soon-Kyung</creatorcontrib><creatorcontrib>CHANG, Seung-Hee</creatorcontrib><creatorcontrib>MINAI-TEHRANI, Arash</creatorcontrib><creatorcontrib>KIM, Yeon-Soo</creatorcontrib><creatorcontrib>CHO, Myung-Haing</creatorcontrib><title>Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice</title><title>Journal of aerosol medicine</title><addtitle>J Aerosol Med Pulm Drug Deliv</addtitle><description>The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer numerous advantages over invasive modes of delivery.
The potential effects of aerosol-delivered lentiviral-based short hairpin AIMP2 lacking exon 2 (shDX2) on lung tumorigenesis were studied. Lentiviral-based shDX2 was delivered into AIMP2(+/-) mice through a nose-only inhalation system twice a week for 4 weeks.
The effects of shDX2 on lung cancer progression and the Akt1-mTOR-p70S6K signaling pathway were evaluated. Long-term repeated delivery of lentiviral-based shDX2 suppressed lung tumor progression significantly by inhibiting Akt1-related signals and decreasing both protein synthesis and angiogenesis. In vivo, the aerosol-mediated application of lentiviral-based short hairpin RNAs was successful in achieving potent and specific knockdown of the target. The collective results indicate the therapeutic potential of the repeated delivery of shDX2 for lung cancer treatment and prevention.</description><subject>Administration, Inhalation</subject><subject>Aerosols</subject><subject>Amino Acyl-tRNA Synthetases - genetics</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation</subject><subject>Disease Progression</subject><subject>Gene Knockdown Techniques</subject><subject>Gene Transfer Techniques</subject><subject>General pharmacology</subject><subject>Lentivirus - genetics</subject><subject>Lung - metabolism</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neovascularization, Pathologic - prevention & control</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>Signal Transduction</subject><issn>1941-2711</issn><issn>1941-2703</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpFkE1P3DAQhi1Exfe1x8oS6gll8dixHR9XS6FIC6z4kLhFTmLveptNgp2A9lCpf6J_kF9CUrZwmhnpmXdGD0JfgYyAJOp0qVfNiBKAEVFcbaE9UDFEVBK2_dED7KL9EJaECIgF20G7lHGQINQe-j01Veuene9CNL68mtHo7JHisLi9HuO7rmm8CcEEPDFliWe-Lp01XreurnC2xrdm3pX9VM3x-FcL-M7NK10O40y3ixe9xq7C7cLgaVfNA64t_nfi5PT1z1985XJziL5YXQZztKkH6OH8x_3kZzS9ubicjKdRzjhrI06EZCopVJLJOM8ZMK4kjUWRUUUp4YwxXiSExYLmhckyIQsQiSScWBuDtewAHb_nNr5-6kxo02Xd-f7XkAITgnHBCPTU6J3KfR2CNzZtvFtpv06BpIPtdLCdDrbTwXa_8G0T22UrU3zg__X2wPcNoEOuS-t1lbvwycmYS9XffwMaNIX4</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>HWANG, Soon-Kyung</creator><creator>CHANG, Seung-Hee</creator><creator>MINAI-TEHRANI, Arash</creator><creator>KIM, Yeon-Soo</creator><creator>CHO, Myung-Haing</creator><general>Mary Ann Liebert</general><general>Mary Ann Liebert, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20130601</creationdate><title>Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice</title><author>HWANG, Soon-Kyung ; CHANG, Seung-Hee ; MINAI-TEHRANI, Arash ; KIM, Yeon-Soo ; CHO, Myung-Haing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-5067398d98b74cc313597246db2922053335d803462cdebb67d1687050ff41ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Administration, Inhalation</topic><topic>Aerosols</topic><topic>Amino Acyl-tRNA Synthetases - genetics</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation</topic><topic>Disease Progression</topic><topic>Gene Knockdown Techniques</topic><topic>Gene Transfer Techniques</topic><topic>General pharmacology</topic><topic>Lentivirus - genetics</topic><topic>Lung - metabolism</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Neovascularization, Pathologic - prevention & control</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HWANG, Soon-Kyung</creatorcontrib><creatorcontrib>CHANG, Seung-Hee</creatorcontrib><creatorcontrib>MINAI-TEHRANI, Arash</creatorcontrib><creatorcontrib>KIM, Yeon-Soo</creatorcontrib><creatorcontrib>CHO, Myung-Haing</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Journal of aerosol medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HWANG, Soon-Kyung</au><au>CHANG, Seung-Hee</au><au>MINAI-TEHRANI, Arash</au><au>KIM, Yeon-Soo</au><au>CHO, Myung-Haing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice</atitle><jtitle>Journal of aerosol medicine</jtitle><addtitle>J Aerosol Med Pulm Drug Deliv</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>26</volume><issue>3</issue><spage>165</spage><epage>173</epage><pages>165-173</pages><issn>1941-2711</issn><eissn>1941-2703</eissn><abstract>The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer numerous advantages over invasive modes of delivery.
The potential effects of aerosol-delivered lentiviral-based short hairpin AIMP2 lacking exon 2 (shDX2) on lung tumorigenesis were studied. Lentiviral-based shDX2 was delivered into AIMP2(+/-) mice through a nose-only inhalation system twice a week for 4 weeks.
The effects of shDX2 on lung cancer progression and the Akt1-mTOR-p70S6K signaling pathway were evaluated. Long-term repeated delivery of lentiviral-based shDX2 suppressed lung tumor progression significantly by inhibiting Akt1-related signals and decreasing both protein synthesis and angiogenesis. In vivo, the aerosol-mediated application of lentiviral-based short hairpin RNAs was successful in achieving potent and specific knockdown of the target. The collective results indicate the therapeutic potential of the repeated delivery of shDX2 for lung cancer treatment and prevention.</abstract><cop>New Rochelle, NY</cop><pub>Mary Ann Liebert</pub><pmid>23517169</pmid><doi>10.1089/jamp.2011.0959</doi><tpages>9</tpages></addata></record> |
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subjects | Administration, Inhalation Aerosols Amino Acyl-tRNA Synthetases - genetics Animals Biological and medical sciences Cell Proliferation Disease Progression Gene Knockdown Techniques Gene Transfer Techniques General pharmacology Lentivirus - genetics Lung - metabolism Lung Neoplasms - genetics Lung Neoplasms - pathology Male Medical sciences Mice Neovascularization, Pathologic - prevention & control Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Proto-Oncogene Proteins c-akt - metabolism RNA, Small Interfering - administration & dosage Signal Transduction |
title | Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice |
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