Liposomal delivery of ferritin heavy chain 1 (FTH1) siRNA in patient xenograft derived glioblastoma initiating cells suggests different sensitivities to radiation and distinct survival mechanisms
Elevated expression of the iron regulatory protein, ferritin heavy chain 1 (FTH1), is increasingly being associated with high tumor grade and poor survival outcomes in glioblastoma. Glioma initiating cells (GICs), a small population of stem-like cells implicated in therapeutic resistance and gliobla...
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| description | Elevated expression of the iron regulatory protein, ferritin heavy chain 1 (FTH1), is increasingly being associated with high tumor grade and poor survival outcomes in glioblastoma. Glioma initiating cells (GICs), a small population of stem-like cells implicated in therapeutic resistance and glioblastoma recurrence, have recently been shown to exhibit increased FTH1 expression. We previously demonstrated that FTH1 knockdown enhanced therapeutic sensitivity in an astrocytoma cell line. Therefore, in this study we developed a liposomal formulation to enable the in vitro delivery of FTH1 siRNA in patient xenograft derived GICs from glioblastomas with pro-neural and mesenchymal transcriptional signatures to interrogate the effect of FTH1 downregulation on their radiation sensitivity. Transfection with siRNA decreased FTH1 expression significantly in both GICs. However, there were inherent differences in transfectability between pro-neural and mesenchymal tumor derived GICs, leading us to modify siRNA: liposome ratios for comparable transfection. Moreover, loss of FTH1 expression resulted in increased extracellular lactate dehydrogenase activity, executioner caspase 3/7 induction, substantial mitochondrial damage, diminished mitochondrial mass and reduced cell viability. However, only GICs from pro-neural glioblastoma showed marked increase in radiosensitivity upon FTH1 downregulation demonstrated by decreased cell viability, impaired DNA repair and reduced colony formation subsequent to radiation. In addition, the stemness marker Nestin was downregulated upon FTH1 silencing only in GICs of pro-neural but not mesenchymal origin. Using liposomes as a siRNA delivery system, we established FTH1 as a critical factor for survival in both GIC subtypes as well as a regulator of radioresistance and stemness in pro-neural tumor derived GICs. Our study provides further evidence to support the role of FTH1 as a promising target in glioblastoma. |
| doi_str_mv | 10.1371/journal.pone.0221952 |
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Glioma initiating cells (GICs), a small population of stem-like cells implicated in therapeutic resistance and glioblastoma recurrence, have recently been shown to exhibit increased FTH1 expression. We previously demonstrated that FTH1 knockdown enhanced therapeutic sensitivity in an astrocytoma cell line. Therefore, in this study we developed a liposomal formulation to enable the in vitro delivery of FTH1 siRNA in patient xenograft derived GICs from glioblastomas with pro-neural and mesenchymal transcriptional signatures to interrogate the effect of FTH1 downregulation on their radiation sensitivity. Transfection with siRNA decreased FTH1 expression significantly in both GICs. However, there were inherent differences in transfectability between pro-neural and mesenchymal tumor derived GICs, leading us to modify siRNA: liposome ratios for comparable transfection. Moreover, loss of FTH1 expression resulted in increased extracellular lactate dehydrogenase activity, executioner caspase 3/7 induction, substantial mitochondrial damage, diminished mitochondrial mass and reduced cell viability. However, only GICs from pro-neural glioblastoma showed marked increase in radiosensitivity upon FTH1 downregulation demonstrated by decreased cell viability, impaired DNA repair and reduced colony formation subsequent to radiation. In addition, the stemness marker Nestin was downregulated upon FTH1 silencing only in GICs of pro-neural but not mesenchymal origin. Using liposomes as a siRNA delivery system, we established FTH1 as a critical factor for survival in both GIC subtypes as well as a regulator of radioresistance and stemness in pro-neural tumor derived GICs. Our study provides further evidence to support the role of FTH1 as a promising target in glioblastoma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0221952</identifier><identifier>PMID: 31491006</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Astrocytoma ; Biology and life sciences ; Blood proteins ; Brain cancer ; Cancer therapies ; Carcinogenesis - pathology ; Caspase ; Caspase-3 ; Cell Line, Tumor ; Cell survival ; Cell Survival - genetics ; Cell Survival - radiation effects ; Cell Transformation, Neoplastic ; Cell viability ; Chains ; Chemotherapy ; Deoxyribonucleic acid ; DNA ; DNA repair ; DNA Repair - genetics ; DNA Repair - radiation effects ; Down-Regulation - genetics ; Ferritin ; Ferritins - deficiency ; Ferritins - genetics ; Genetic research ; Glioblastoma ; Glioblastoma - genetics ; Glioblastoma - pathology ; Glioblastomas ; Glioma cells ; Gliomas ; Growth factors ; Humans ; Immunoglobulins ; Iron ; Iron regulatory protein ; Kinases ; L-Lactate dehydrogenase ; Lactate dehydrogenase ; Lactic acid ; Lipids ; Liposomes ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Mesenchyme ; Mitochondria ; Nestin ; Neurosurgery ; Oxidoreductases - deficiency ; Oxidoreductases - genetics ; Radiation ; Radiation (Physics) ; Radiation Tolerance - genetics ; Radioresistance ; Radiosensitivity ; Research and Analysis Methods ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - genetics ; Sensitivity ; Sensitivity enhancement ; siRNA ; Stem cells ; Survival ; Transcription ; Transfection ; Tumors ; Xenografts ; Xenotransplantation</subject><ispartof>PloS one, 2019-09, Vol.14 (9), p.e0221952</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Ravi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Ravi et al 2019 Ravi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-bd236737634e5f94d682391351d2f9de887e08d588f07f154dd98299a36c76fd3</citedby><cites>FETCH-LOGICAL-c593t-bd236737634e5f94d682391351d2f9de887e08d588f07f154dd98299a36c76fd3</cites><orcidid>0000-0003-0750-8774 ; 0000-0002-8492-3093</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730865/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730865/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31491006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ulasov, Ilya</contributor><creatorcontrib>Ravi, Vagisha</creatorcontrib><creatorcontrib>Madhankumar, Achuthamangalam B</creatorcontrib><creatorcontrib>Abraham, Thomas</creatorcontrib><creatorcontrib>Slagle-Webb, Becky</creatorcontrib><creatorcontrib>Connor, James R</creatorcontrib><title>Liposomal delivery of ferritin heavy chain 1 (FTH1) siRNA in patient xenograft derived glioblastoma initiating cells suggests different sensitivities to radiation and distinct survival mechanisms</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Elevated expression of the iron regulatory protein, ferritin heavy chain 1 (FTH1), is increasingly being associated with high tumor grade and poor survival outcomes in glioblastoma. Glioma initiating cells (GICs), a small population of stem-like cells implicated in therapeutic resistance and glioblastoma recurrence, have recently been shown to exhibit increased FTH1 expression. We previously demonstrated that FTH1 knockdown enhanced therapeutic sensitivity in an astrocytoma cell line. Therefore, in this study we developed a liposomal formulation to enable the in vitro delivery of FTH1 siRNA in patient xenograft derived GICs from glioblastomas with pro-neural and mesenchymal transcriptional signatures to interrogate the effect of FTH1 downregulation on their radiation sensitivity. Transfection with siRNA decreased FTH1 expression significantly in both GICs. However, there were inherent differences in transfectability between pro-neural and mesenchymal tumor derived GICs, leading us to modify siRNA: liposome ratios for comparable transfection. Moreover, loss of FTH1 expression resulted in increased extracellular lactate dehydrogenase activity, executioner caspase 3/7 induction, substantial mitochondrial damage, diminished mitochondrial mass and reduced cell viability. However, only GICs from pro-neural glioblastoma showed marked increase in radiosensitivity upon FTH1 downregulation demonstrated by decreased cell viability, impaired DNA repair and reduced colony formation subsequent to radiation. In addition, the stemness marker Nestin was downregulated upon FTH1 silencing only in GICs of pro-neural but not mesenchymal origin. Using liposomes as a siRNA delivery system, we established FTH1 as a critical factor for survival in both GIC subtypes as well as a regulator of radioresistance and stemness in pro-neural tumor derived GICs. 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genetics</subject><subject>Genetic research</subject><subject>Glioblastoma</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastomas</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Iron</subject><subject>Iron regulatory protein</subject><subject>Kinases</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Lipids</subject><subject>Liposomes</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchyme</subject><subject>Mitochondria</subject><subject>Nestin</subject><subject>Neurosurgery</subject><subject>Oxidoreductases - deficiency</subject><subject>Oxidoreductases - genetics</subject><subject>Radiation</subject><subject>Radiation (Physics)</subject><subject>Radiation Tolerance - genetics</subject><subject>Radioresistance</subject><subject>Radiosensitivity</subject><subject>Research and Analysis Methods</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>Sensitivity</subject><subject>Sensitivity enhancement</subject><subject>siRNA</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Transcription</subject><subject>Transfection</subject><subject>Tumors</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1kt-KEzEUxgdR3HX1DUQD3uhF6yRpMsmNUBbXXSgKsl6HNH-mWWaSmkwH-3y-mKd2dtmCEsKEM9_3O1_CqarXuJ5j2uCPd2mXo-7m2xTdvCYES0aeVOdYUjLjpKZPH53Pqhel3NU1o4Lz59UZxQuJ65qfV79XYZtK6nWHrOvC6PIeJY-8yzkMIaKN0-MemY2GM0bvr26v8QdUwvevSwSVrR6CiwP65WJqs_YDQDJALGq7kNadLgOgQQkskMYWGdd1BZVd27oyFGSDh1YHRHGxgGqE7QoaEsraHjwpIh0tCAv4Deh2eQwjxO0dpIqh9OVl9czrrrhX0_ei-nH1-fbyerb69uXmcrmaGSbpMFtbQnlDG04Xjnm5sFwQKjFl2BIvrROicbWwTAhfNx6zhbVSECk15abh3tKL6u2Ru-1SUdP7F0WIYA3mtGlAcXNU2KTv1DaHXue9Sjqov4WUW6XzEEznlHBWUljSMrcQArpLQxnBxBCLPXfA-jR12617Zw08UtbdCfT0Twwb1aZRwR1rwRkA3k2AnH7u4Ln_E3lStRpShegTwEwfilFLJgUTjPCDav4PFSzr-mBgAn2A-olhcTSYnErJzj8Ex7U6zO99GHWYXzXNL9jePL70g-l-YOkf32Hxmg</recordid><startdate>20190906</startdate><enddate>20190906</enddate><creator>Ravi, Vagisha</creator><creator>Madhankumar, Achuthamangalam B</creator><creator>Abraham, Thomas</creator><creator>Slagle-Webb, Becky</creator><creator>Connor, James R</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0750-8774</orcidid><orcidid>https://orcid.org/0000-0002-8492-3093</orcidid></search><sort><creationdate>20190906</creationdate><title>Liposomal delivery of ferritin heavy chain 1 (FTH1) siRNA in patient xenograft derived glioblastoma initiating cells suggests different sensitivities to radiation and distinct survival mechanisms</title><author>Ravi, Vagisha ; Madhankumar, Achuthamangalam B ; Abraham, Thomas ; Slagle-Webb, Becky ; Connor, James R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-bd236737634e5f94d682391351d2f9de887e08d588f07f154dd98299a36c76fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Astrocytoma</topic><topic>Biology and life sciences</topic><topic>Blood proteins</topic><topic>Brain cancer</topic><topic>Cancer therapies</topic><topic>Carcinogenesis - 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deficiency</topic><topic>Oxidoreductases - genetics</topic><topic>Radiation</topic><topic>Radiation (Physics)</topic><topic>Radiation Tolerance - genetics</topic><topic>Radioresistance</topic><topic>Radiosensitivity</topic><topic>Research and Analysis Methods</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>Sensitivity</topic><topic>Sensitivity enhancement</topic><topic>siRNA</topic><topic>Stem cells</topic><topic>Survival</topic><topic>Transcription</topic><topic>Transfection</topic><topic>Tumors</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ravi, Vagisha</creatorcontrib><creatorcontrib>Madhankumar, Achuthamangalam B</creatorcontrib><creatorcontrib>Abraham, Thomas</creatorcontrib><creatorcontrib>Slagle-Webb, Becky</creatorcontrib><creatorcontrib>Connor, James R</creatorcontrib><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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Glioma initiating cells (GICs), a small population of stem-like cells implicated in therapeutic resistance and glioblastoma recurrence, have recently been shown to exhibit increased FTH1 expression. We previously demonstrated that FTH1 knockdown enhanced therapeutic sensitivity in an astrocytoma cell line. Therefore, in this study we developed a liposomal formulation to enable the in vitro delivery of FTH1 siRNA in patient xenograft derived GICs from glioblastomas with pro-neural and mesenchymal transcriptional signatures to interrogate the effect of FTH1 downregulation on their radiation sensitivity. Transfection with siRNA decreased FTH1 expression significantly in both GICs. However, there were inherent differences in transfectability between pro-neural and mesenchymal tumor derived GICs, leading us to modify siRNA: liposome ratios for comparable transfection. Moreover, loss of FTH1 expression resulted in increased extracellular lactate dehydrogenase activity, executioner caspase 3/7 induction, substantial mitochondrial damage, diminished mitochondrial mass and reduced cell viability. However, only GICs from pro-neural glioblastoma showed marked increase in radiosensitivity upon FTH1 downregulation demonstrated by decreased cell viability, impaired DNA repair and reduced colony formation subsequent to radiation. In addition, the stemness marker Nestin was downregulated upon FTH1 silencing only in GICs of pro-neural but not mesenchymal origin. Using liposomes as a siRNA delivery system, we established FTH1 as a critical factor for survival in both GIC subtypes as well as a regulator of radioresistance and stemness in pro-neural tumor derived GICs. Our study provides further evidence to support the role of FTH1 as a promising target in glioblastoma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31491006</pmid><doi>10.1371/journal.pone.0221952</doi><orcidid>https://orcid.org/0000-0003-0750-8774</orcidid><orcidid>https://orcid.org/0000-0002-8492-3093</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-09, Vol.14 (9), p.e0221952 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2285716377 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Astrocytoma Biology and life sciences Blood proteins Brain cancer Cancer therapies Carcinogenesis - pathology Caspase Caspase-3 Cell Line, Tumor Cell survival Cell Survival - genetics Cell Survival - radiation effects Cell Transformation, Neoplastic Cell viability Chains Chemotherapy Deoxyribonucleic acid DNA DNA repair DNA Repair - genetics DNA Repair - radiation effects Down-Regulation - genetics Ferritin Ferritins - deficiency Ferritins - genetics Genetic research Glioblastoma Glioblastoma - genetics Glioblastoma - pathology Glioblastomas Glioma cells Gliomas Growth factors Humans Immunoglobulins Iron Iron regulatory protein Kinases L-Lactate dehydrogenase Lactate dehydrogenase Lactic acid Lipids Liposomes Medical prognosis Medicine Medicine and Health Sciences Mesenchyme Mitochondria Nestin Neurosurgery Oxidoreductases - deficiency Oxidoreductases - genetics Radiation Radiation (Physics) Radiation Tolerance - genetics Radioresistance Radiosensitivity Research and Analysis Methods RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics Sensitivity Sensitivity enhancement siRNA Stem cells Survival Transcription Transfection Tumors Xenografts Xenotransplantation |
| title | Liposomal delivery of ferritin heavy chain 1 (FTH1) siRNA in patient xenograft derived glioblastoma initiating cells suggests different sensitivities to radiation and distinct survival mechanisms |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T06%3A00%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Liposomal%20delivery%20of%20ferritin%20heavy%20chain%201%20(FTH1)%20siRNA%20in%20patient%20xenograft%20derived%20glioblastoma%20initiating%20cells%20suggests%20different%20sensitivities%20to%20radiation%20and%20distinct%20survival%20mechanisms&rft.jtitle=PloS%20one&rft.au=Ravi,%20Vagisha&rft.date=2019-09-06&rft.volume=14&rft.issue=9&rft.spage=e0221952&rft.pages=e0221952-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0221952&rft_dat=%3Cgale_plos_%3EA598585267%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2285716377&rft_id=info:pmid/31491006&rft_galeid=A598585267&rft_doaj_id=oai_doaj_org_article_8ed939399d5e488e889c35212c2d1f6e&rfr_iscdi=true |