Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial–mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma
The high invasiveness and frequent recurrence of lung adenocarcinoma (LAC) are major reasons for treatment failures and poor prognoses. Alterations in microRNAs (miRNAs) expression have been shown in lung cancers. Recent reports have demonstrated that tumors contain a small subpopulation of cancer s...
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creator | Chiou, Guang-Yuh Cherng, Jong-Yuh Hsu, Han-Shui Wang, Mong-Lien Tsai, Chun-Ming Lu, Kai-Hsi Chien, Yueh Hung, Shih-Chieh Chen, Yi-Wei Wong, Chiang-Ing Tseng, Ling-Ming Huang, Pin-I Yu, Cheng-Chia Hsu, Wen-Huh Chiou, Shih-Hwa |
description | The high invasiveness and frequent recurrence of lung adenocarcinoma (LAC) are major reasons for treatment failures and poor prognoses. Alterations in microRNAs (miRNAs) expression have been shown in lung cancers. Recent reports have demonstrated that tumors contain a small subpopulation of cancer stem cells (CSCs) that possesses self-renewing capacity and is responsible for tumor malignancy including metastasis, relapse, and chemoradioresistance. However, a miRNAs-based therapeutic approach in LAC-associated CSCs (LAC-CSCs) is still blurred. Using miRNA/mRNA-microarray and Quantitative RT-PCR, we found that the expression of miR145 is negatively correlated with the levels of Oct4/Sox2/Fascin1 in LAC patient specimens, and an Oct4highSox2highFascin1highmiR145low phenotype predicted poor prognosis. We enriched LAC-CSCs by side population sorting or identification of CD133 markers and found that LAC-CSCs exhibited low miR145 and high Oct4/Sox2/Fascin1 expression, CSC-like properties, and chemoradioresistance. To clarify the role of miR145, we used a polyurethane-short branch-polyethylenimine (PU-PEI) as the vehicle to deliver miR145 into LAC-CSCs. PU-PEI-mediated miR145 delivery reduced CSC-like properties, and improved chemoradioresistance in LAC-CSCs by directly targeting Oct4/Sox2/Fascin1. Importantly, the repressive effect of miR145 on tumor metastasis was mediated by inhibiting the epithelial–mesenchymal transdifferentiation (EMT) and metastastic ability, partially by regulating Oct4/Sox2/Fascin1, Tcf4, and Wnt5a. Finally, in vivo study showed that PU-PEI-mediated miR145 delivery to xenograft tumors reduced tumor growth and metastasis, sensitized tumors to chemoradiotherapies, and prolonged the survival times of tumor-bearing mice. Our results demonstrated that miR145 acts as a switch regulating lung CSC-like and EMT properties, and provide insights into the clinical prospect of miR145-based therapies for malignant lung cancers.
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doi_str_mv | 10.1016/j.jconrel.2012.01.014 |
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[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2012.01.014</identifier><identifier>PMID: 22285547</identifier><identifier>CODEN: JCREEC</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>adenocarcinoma ; Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Adenocarcinoma of Lung ; Animals ; Biological and medical sciences ; Cations ; Cell Culture Techniques ; Cell Movement - drug effects ; Cell Movement - radiation effects ; Cell Survival - drug effects ; Cell Survival - genetics ; Cell Transdifferentiation ; Cells, Cultured ; correlation ; Drug Carriers - chemistry ; Epithelial-Mesenchymal Transition - drug effects ; Epithelial-Mesenchymal Transition - genetics ; Epithelial–mesenchymal transdifferentiation ; Fascin1 ; Gamma Rays ; Gene Transfer Techniques ; General pharmacology ; Humans ; in vivo studies ; Lung adenocarcinoma ; lung neoplasms ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Medical sciences ; metastasis ; Mice ; Mice, Nude ; microRNA ; MicroRNAs - administration & dosage ; MicroRNAs - genetics ; MicroRNAs - therapeutic use ; miR145 ; Neoplasm Invasiveness ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - pathology ; Oct4 ; patients ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; phenotype ; Polyethyleneimine - chemistry ; Polyurethanes - chemistry ; prognosis ; relapse ; reverse transcriptase polymerase chain reaction ; sorting ; Sox2 ; stem cells ; Tumor Stem Cell Assay</subject><ispartof>Journal of controlled release, 2012-04, Vol.159 (2), p.240-250</ispartof><rights>2012</rights><rights>2015 INIST-CNRS</rights><rights>Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-1239b5db52074ed3ad5f4ab69d6d873403529dea2bf5c94d5e6dd1861380bc2a3</citedby><cites>FETCH-LOGICAL-c419t-1239b5db52074ed3ad5f4ab69d6d873403529dea2bf5c94d5e6dd1861380bc2a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168365912000193$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25912957$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22285547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chiou, Guang-Yuh</creatorcontrib><creatorcontrib>Cherng, Jong-Yuh</creatorcontrib><creatorcontrib>Hsu, Han-Shui</creatorcontrib><creatorcontrib>Wang, Mong-Lien</creatorcontrib><creatorcontrib>Tsai, Chun-Ming</creatorcontrib><creatorcontrib>Lu, Kai-Hsi</creatorcontrib><creatorcontrib>Chien, Yueh</creatorcontrib><creatorcontrib>Hung, Shih-Chieh</creatorcontrib><creatorcontrib>Chen, Yi-Wei</creatorcontrib><creatorcontrib>Wong, Chiang-Ing</creatorcontrib><creatorcontrib>Tseng, Ling-Ming</creatorcontrib><creatorcontrib>Huang, Pin-I</creatorcontrib><creatorcontrib>Yu, Cheng-Chia</creatorcontrib><creatorcontrib>Hsu, Wen-Huh</creatorcontrib><creatorcontrib>Chiou, Shih-Hwa</creatorcontrib><title>Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial–mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>The high invasiveness and frequent recurrence of lung adenocarcinoma (LAC) are major reasons for treatment failures and poor prognoses. Alterations in microRNAs (miRNAs) expression have been shown in lung cancers. Recent reports have demonstrated that tumors contain a small subpopulation of cancer stem cells (CSCs) that possesses self-renewing capacity and is responsible for tumor malignancy including metastasis, relapse, and chemoradioresistance. However, a miRNAs-based therapeutic approach in LAC-associated CSCs (LAC-CSCs) is still blurred. Using miRNA/mRNA-microarray and Quantitative RT-PCR, we found that the expression of miR145 is negatively correlated with the levels of Oct4/Sox2/Fascin1 in LAC patient specimens, and an Oct4highSox2highFascin1highmiR145low phenotype predicted poor prognosis. We enriched LAC-CSCs by side population sorting or identification of CD133 markers and found that LAC-CSCs exhibited low miR145 and high Oct4/Sox2/Fascin1 expression, CSC-like properties, and chemoradioresistance. To clarify the role of miR145, we used a polyurethane-short branch-polyethylenimine (PU-PEI) as the vehicle to deliver miR145 into LAC-CSCs. PU-PEI-mediated miR145 delivery reduced CSC-like properties, and improved chemoradioresistance in LAC-CSCs by directly targeting Oct4/Sox2/Fascin1. Importantly, the repressive effect of miR145 on tumor metastasis was mediated by inhibiting the epithelial–mesenchymal transdifferentiation (EMT) and metastastic ability, partially by regulating Oct4/Sox2/Fascin1, Tcf4, and Wnt5a. Finally, in vivo study showed that PU-PEI-mediated miR145 delivery to xenograft tumors reduced tumor growth and metastasis, sensitized tumors to chemoradiotherapies, and prolonged the survival times of tumor-bearing mice. Our results demonstrated that miR145 acts as a switch regulating lung CSC-like and EMT properties, and provide insights into the clinical prospect of miR145-based therapies for malignant lung cancers.
[Display omitted]</description><subject>adenocarcinoma</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma of Lung</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cations</subject><subject>Cell Culture Techniques</subject><subject>Cell Movement - drug effects</subject><subject>Cell Movement - radiation effects</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - genetics</subject><subject>Cell Transdifferentiation</subject><subject>Cells, Cultured</subject><subject>correlation</subject><subject>Drug Carriers - chemistry</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Epithelial–mesenchymal transdifferentiation</subject><subject>Fascin1</subject><subject>Gamma Rays</subject><subject>Gene Transfer Techniques</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>in vivo studies</subject><subject>Lung adenocarcinoma</subject><subject>lung neoplasms</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Medical sciences</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>microRNA</subject><subject>MicroRNAs - administration & dosage</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - therapeutic use</subject><subject>miR145</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Oct4</subject><subject>patients</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>phenotype</subject><subject>Polyethyleneimine - chemistry</subject><subject>Polyurethanes - chemistry</subject><subject>prognosis</subject><subject>relapse</subject><subject>reverse transcriptase polymerase chain reaction</subject><subject>sorting</subject><subject>Sox2</subject><subject>stem cells</subject><subject>Tumor Stem Cell Assay</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGO0zAQhiMEYsvCIwC-IHFJsR3baU4IVQustAgk2HPk2JOti2MX212pN96Bd-GBeBIm2wJHpJHmMN_MP_r_qnrK6JJRpl5tl1sTQwK_5JTxJWVY4l61YKu2qUXXyfvVArlV3SjZnVWPct5SSmUj2ofVGed8JaVoF9XPtS4uBmfILvrDPkHZ6AC5zpuYChmSDmZDPl1c1hNYpwtYYsG7W0gHEkfywSUmJHFh4wY3D2HnygYB7X99_zFBBlw_TNqTgpeydeMICUJxd6JEB0sMKkAiucBUe_cVyC7FHaTiIN_NXSB-H26IthCi0cm4ECf9uHowap_hyamfV9dvL76s39dXH99drt9c1UawrtSMN90g7SA5bQXYRls5Cj2oziqLPgnaSN5Z0HwYpemElaCsZSvFmhUdDNfNefXyeBe_-raHXPrJZQPeo0lxn3uMomkVU5IjKo-oSTHnBGO_S27S6YDQzKl-258i6-fIesqwBO49O0nsBzT579afjBB4cQJ0NtqPcyYu_-Nkx3gnZ-75kRt17PVNQub6MypJSlmrFJ9ffH0kAC27dZD6bBxGhNEmMKW30f3n2d__1cZk</recordid><startdate>20120430</startdate><enddate>20120430</enddate><creator>Chiou, Guang-Yuh</creator><creator>Cherng, Jong-Yuh</creator><creator>Hsu, Han-Shui</creator><creator>Wang, Mong-Lien</creator><creator>Tsai, Chun-Ming</creator><creator>Lu, Kai-Hsi</creator><creator>Chien, Yueh</creator><creator>Hung, Shih-Chieh</creator><creator>Chen, Yi-Wei</creator><creator>Wong, Chiang-Ing</creator><creator>Tseng, Ling-Ming</creator><creator>Huang, Pin-I</creator><creator>Yu, Cheng-Chia</creator><creator>Hsu, Wen-Huh</creator><creator>Chiou, Shih-Hwa</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><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>7X8</scope></search><sort><creationdate>20120430</creationdate><title>Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial–mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma</title><author>Chiou, Guang-Yuh ; Cherng, Jong-Yuh ; Hsu, Han-Shui ; Wang, Mong-Lien ; Tsai, Chun-Ming ; Lu, Kai-Hsi ; Chien, Yueh ; Hung, Shih-Chieh ; Chen, Yi-Wei ; Wong, Chiang-Ing ; Tseng, Ling-Ming ; Huang, Pin-I ; Yu, Cheng-Chia ; Hsu, Wen-Huh ; Chiou, Shih-Hwa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-1239b5db52074ed3ad5f4ab69d6d873403529dea2bf5c94d5e6dd1861380bc2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>adenocarcinoma</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma of Lung</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cations</topic><topic>Cell Culture Techniques</topic><topic>Cell Movement - drug effects</topic><topic>Cell Movement - radiation effects</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - genetics</topic><topic>Cell Transdifferentiation</topic><topic>Cells, Cultured</topic><topic>correlation</topic><topic>Drug Carriers - chemistry</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Epithelial–mesenchymal transdifferentiation</topic><topic>Fascin1</topic><topic>Gamma Rays</topic><topic>Gene Transfer Techniques</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>in vivo studies</topic><topic>Lung adenocarcinoma</topic><topic>lung neoplasms</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Medical sciences</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>microRNA</topic><topic>MicroRNAs - administration & dosage</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - therapeutic use</topic><topic>miR145</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Oct4</topic><topic>patients</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>phenotype</topic><topic>Polyethyleneimine - chemistry</topic><topic>Polyurethanes - chemistry</topic><topic>prognosis</topic><topic>relapse</topic><topic>reverse transcriptase polymerase chain reaction</topic><topic>sorting</topic><topic>Sox2</topic><topic>stem cells</topic><topic>Tumor Stem Cell Assay</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiou, Guang-Yuh</creatorcontrib><creatorcontrib>Cherng, Jong-Yuh</creatorcontrib><creatorcontrib>Hsu, Han-Shui</creatorcontrib><creatorcontrib>Wang, Mong-Lien</creatorcontrib><creatorcontrib>Tsai, Chun-Ming</creatorcontrib><creatorcontrib>Lu, Kai-Hsi</creatorcontrib><creatorcontrib>Chien, Yueh</creatorcontrib><creatorcontrib>Hung, Shih-Chieh</creatorcontrib><creatorcontrib>Chen, Yi-Wei</creatorcontrib><creatorcontrib>Wong, Chiang-Ing</creatorcontrib><creatorcontrib>Tseng, Ling-Ming</creatorcontrib><creatorcontrib>Huang, Pin-I</creatorcontrib><creatorcontrib>Yu, Cheng-Chia</creatorcontrib><creatorcontrib>Hsu, Wen-Huh</creatorcontrib><creatorcontrib>Chiou, Shih-Hwa</creatorcontrib><collection>AGRIS</collection><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>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chiou, Guang-Yuh</au><au>Cherng, Jong-Yuh</au><au>Hsu, Han-Shui</au><au>Wang, Mong-Lien</au><au>Tsai, Chun-Ming</au><au>Lu, Kai-Hsi</au><au>Chien, Yueh</au><au>Hung, Shih-Chieh</au><au>Chen, Yi-Wei</au><au>Wong, Chiang-Ing</au><au>Tseng, Ling-Ming</au><au>Huang, Pin-I</au><au>Yu, Cheng-Chia</au><au>Hsu, Wen-Huh</au><au>Chiou, Shih-Hwa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial–mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2012-04-30</date><risdate>2012</risdate><volume>159</volume><issue>2</issue><spage>240</spage><epage>250</epage><pages>240-250</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><coden>JCREEC</coden><abstract>The high invasiveness and frequent recurrence of lung adenocarcinoma (LAC) are major reasons for treatment failures and poor prognoses. Alterations in microRNAs (miRNAs) expression have been shown in lung cancers. Recent reports have demonstrated that tumors contain a small subpopulation of cancer stem cells (CSCs) that possesses self-renewing capacity and is responsible for tumor malignancy including metastasis, relapse, and chemoradioresistance. However, a miRNAs-based therapeutic approach in LAC-associated CSCs (LAC-CSCs) is still blurred. Using miRNA/mRNA-microarray and Quantitative RT-PCR, we found that the expression of miR145 is negatively correlated with the levels of Oct4/Sox2/Fascin1 in LAC patient specimens, and an Oct4highSox2highFascin1highmiR145low phenotype predicted poor prognosis. We enriched LAC-CSCs by side population sorting or identification of CD133 markers and found that LAC-CSCs exhibited low miR145 and high Oct4/Sox2/Fascin1 expression, CSC-like properties, and chemoradioresistance. To clarify the role of miR145, we used a polyurethane-short branch-polyethylenimine (PU-PEI) as the vehicle to deliver miR145 into LAC-CSCs. PU-PEI-mediated miR145 delivery reduced CSC-like properties, and improved chemoradioresistance in LAC-CSCs by directly targeting Oct4/Sox2/Fascin1. Importantly, the repressive effect of miR145 on tumor metastasis was mediated by inhibiting the epithelial–mesenchymal transdifferentiation (EMT) and metastastic ability, partially by regulating Oct4/Sox2/Fascin1, Tcf4, and Wnt5a. Finally, in vivo study showed that PU-PEI-mediated miR145 delivery to xenograft tumors reduced tumor growth and metastasis, sensitized tumors to chemoradiotherapies, and prolonged the survival times of tumor-bearing mice. Our results demonstrated that miR145 acts as a switch regulating lung CSC-like and EMT properties, and provide insights into the clinical prospect of miR145-based therapies for malignant lung cancers.
[Display omitted]</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>22285547</pmid><doi>10.1016/j.jconrel.2012.01.014</doi><tpages>11</tpages></addata></record> |
fulltext | fulltext |
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language | eng |
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source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | adenocarcinoma Adenocarcinoma - drug therapy Adenocarcinoma - genetics Adenocarcinoma - pathology Adenocarcinoma of Lung Animals Biological and medical sciences Cations Cell Culture Techniques Cell Movement - drug effects Cell Movement - radiation effects Cell Survival - drug effects Cell Survival - genetics Cell Transdifferentiation Cells, Cultured correlation Drug Carriers - chemistry Epithelial-Mesenchymal Transition - drug effects Epithelial-Mesenchymal Transition - genetics Epithelial–mesenchymal transdifferentiation Fascin1 Gamma Rays Gene Transfer Techniques General pharmacology Humans in vivo studies Lung adenocarcinoma lung neoplasms Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - pathology Medical sciences metastasis Mice Mice, Nude microRNA MicroRNAs - administration & dosage MicroRNAs - genetics MicroRNAs - therapeutic use miR145 Neoplasm Invasiveness Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - pathology Oct4 patients Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments phenotype Polyethyleneimine - chemistry Polyurethanes - chemistry prognosis relapse reverse transcriptase polymerase chain reaction sorting Sox2 stem cells Tumor Stem Cell Assay |
title | Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial–mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T22%3A37%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cationic%20polyurethanes-short%20branch%20PEI-mediated%20delivery%20of%20Mir145%20inhibited%20epithelial%E2%80%93mesenchymal%20transdifferentiation%20and%20cancer%20stem-like%20properties%20and%20in%20lung%20adenocarcinoma&rft.jtitle=Journal%20of%20controlled%20release&rft.au=Chiou,%20Guang-Yuh&rft.date=2012-04-30&rft.volume=159&rft.issue=2&rft.spage=240&rft.epage=250&rft.pages=240-250&rft.issn=0168-3659&rft.eissn=1873-4995&rft.coden=JCREEC&rft_id=info:doi/10.1016/j.jconrel.2012.01.014&rft_dat=%3Cproquest_cross%3E1013761652%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1013761652&rft_id=info:pmid/22285547&rft_els_id=S0168365912000193&rfr_iscdi=true |