Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma
Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was...
Gespeichert in:
| Veröffentlicht in: | Human gene therapy 2011-09, Vol.22 (9), p.1109-1119 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1119 |
|---|---|
| container_issue | 9 |
| container_start_page | 1109 |
| container_title | Human gene therapy |
| container_volume | 22 |
| creator | WEI, Rui-Cheng XIN CAO GUI, Jing-Hua ZHOU, Xiu-Mei DAN ZHONG YAN, Qiao-Lin HUANG, Wei-Dan QIAN, Qi-Jun ZHAO, Feng-Li LIU, Xin-Yuan |
| description | Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively. The combined treatment of AFP-D55-SOCS3 and AFP-D55-TRAIL (2:3 ratio) exhibited potent antitumor activity in AFP-positive HCC cell lines compared with any other treatment both in vitro and in vivo. Specific replication and low progeny yield in AFP-positive HCC cell lines rendered these double-regulated oncolytic adenoviruses remarkably safe. Our data demonstrated that restoration of SOCS3, which inhibits the JAK/STAT3 pathway, by AFP-D55-SOCS3 not only could antagonize HCC therapeutic resistance to TRAIL and adenoviruses, but could also induce cell cycle arrest in HCC cell lines. SOCS3 could down-regulate Cyclin D1 and anti-apoptotic proteins such as XIAP, Survivin, Bcl-xL, and Mcl-1, which are responsible for the synergistic inhibitory effects of AFP-D55-SOCS3 and AFP-D55-TRAIL. Dual gene and double-regulated oncolytic adenoviruses may provide safety and excellent antitumor effects for liver cancer, which is the advantage of a cancer-targeting gene virotherapy strategy. |
| doi_str_mv | 10.1089/hum.2010.219 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_902368569</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A268790271</galeid><sourcerecordid>A268790271</sourcerecordid><originalsourceid>FETCH-LOGICAL-c419t-179e9081459e288e21dd898c58336b7372d1c8918ff3ca47ce7bc4e96452e33d3</originalsourceid><addsrcrecordid>eNqFkc-L1DAUx4so7rp68ywBES92zK-2ybGMq7swMDC7nkuavsxE2mRM0pW5-4ebcUZFECSHvDw-35cv71sULwleECzk-908LSjOL0rko-KSVFVTNpzSx7nGnJWYcXpRPIvxC8aEVXXztLighNWkkfiy-N7O2wlcsm6L0g5Qm8s0Tz6ga2NAJ-QNut-0tyvUH9DdennH0DebduiDn_sRyg1s51ElGNAG9qPV6uegtdN-PCSrUTuA8w82zBFZh25gr5LXMI5ZFNBSBW2dn9Tz4olRY4QX5_uq-Pzx-n55U67Wn26X7arUnMhUZscgsSC8kkCFAEqGQUihK8FY3TesoQPRQhJhDNOKNxqaXnOQNa8oMDawq-Ltae4--K8zxNRNNh7tKAd-jp3ElNWiquV_SSHzb6QhOJOvT-RWjdBZZ3wKSh_prqW1yEumDcnU4h9UPgNMVnsHxub-X4J3J4EOPsYAptsHO6lw6Ajujrl3OffumHuXc8_4q7PfuZ9g-A3_CjoDb86AilqNJiinbfzD8UrUjHL2A5ycs-U</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>893721710</pqid></control><display><type>article</type><title>Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>WEI, Rui-Cheng ; XIN CAO ; GUI, Jing-Hua ; ZHOU, Xiu-Mei ; DAN ZHONG ; YAN, Qiao-Lin ; HUANG, Wei-Dan ; QIAN, Qi-Jun ; ZHAO, Feng-Li ; LIU, Xin-Yuan</creator><creatorcontrib>WEI, Rui-Cheng ; XIN CAO ; GUI, Jing-Hua ; ZHOU, Xiu-Mei ; DAN ZHONG ; YAN, Qiao-Lin ; HUANG, Wei-Dan ; QIAN, Qi-Jun ; ZHAO, Feng-Li ; LIU, Xin-Yuan</creatorcontrib><description>Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively. The combined treatment of AFP-D55-SOCS3 and AFP-D55-TRAIL (2:3 ratio) exhibited potent antitumor activity in AFP-positive HCC cell lines compared with any other treatment both in vitro and in vivo. Specific replication and low progeny yield in AFP-positive HCC cell lines rendered these double-regulated oncolytic adenoviruses remarkably safe. Our data demonstrated that restoration of SOCS3, which inhibits the JAK/STAT3 pathway, by AFP-D55-SOCS3 not only could antagonize HCC therapeutic resistance to TRAIL and adenoviruses, but could also induce cell cycle arrest in HCC cell lines. SOCS3 could down-regulate Cyclin D1 and anti-apoptotic proteins such as XIAP, Survivin, Bcl-xL, and Mcl-1, which are responsible for the synergistic inhibitory effects of AFP-D55-SOCS3 and AFP-D55-TRAIL. Dual gene and double-regulated oncolytic adenoviruses may provide safety and excellent antitumor effects for liver cancer, which is the advantage of a cancer-targeting gene virotherapy strategy.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2010.219</identifier><identifier>PMID: 21361790</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject>Adenoviridae - genetics ; Adenovirus ; alpha-Fetoproteins - genetics ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Apoptosis - genetics ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biotechnology ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - therapy ; Care and treatment ; Cell Line, Tumor ; Cellular signal transduction ; Cytopathogenic Effect, Viral ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene therapy ; Genetic aspects ; Genetic Therapy ; Genetic Vectors - administration & dosage ; Genetic Vectors - toxicity ; Health aspects ; Health. Pharmaceutical industry ; HEK293 Cells ; HeLa Cells ; Hep G2 Cells ; Hepatoma ; HT29 Cells ; Humans ; Industrial applications and implications. Economical aspects ; Kaplan-Meier Estimate ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - therapy ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oncolytic Virotherapy ; Oncolytic Viruses - genetics ; Physiological aspects ; Promoter Regions, Genetic ; Protein kinases ; Suppressor of Cytokine Signaling Proteins - genetics ; Suppressor of Cytokine Signaling Proteins - metabolism ; TNF-Related Apoptosis-Inducing Ligand - genetics ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tumor Burden - genetics ; Virus Replication ; Xenograft Model Antitumor Assays</subject><ispartof>Human gene therapy, 2011-09, Vol.22 (9), p.1109-1119</ispartof><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-179e9081459e288e21dd898c58336b7372d1c8918ff3ca47ce7bc4e96452e33d3</citedby><cites>FETCH-LOGICAL-c419t-179e9081459e288e21dd898c58336b7372d1c8918ff3ca47ce7bc4e96452e33d3</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=24586324$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21361790$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WEI, Rui-Cheng</creatorcontrib><creatorcontrib>XIN CAO</creatorcontrib><creatorcontrib>GUI, Jing-Hua</creatorcontrib><creatorcontrib>ZHOU, Xiu-Mei</creatorcontrib><creatorcontrib>DAN ZHONG</creatorcontrib><creatorcontrib>YAN, Qiao-Lin</creatorcontrib><creatorcontrib>HUANG, Wei-Dan</creatorcontrib><creatorcontrib>QIAN, Qi-Jun</creatorcontrib><creatorcontrib>ZHAO, Feng-Li</creatorcontrib><creatorcontrib>LIU, Xin-Yuan</creatorcontrib><title>Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively. The combined treatment of AFP-D55-SOCS3 and AFP-D55-TRAIL (2:3 ratio) exhibited potent antitumor activity in AFP-positive HCC cell lines compared with any other treatment both in vitro and in vivo. Specific replication and low progeny yield in AFP-positive HCC cell lines rendered these double-regulated oncolytic adenoviruses remarkably safe. Our data demonstrated that restoration of SOCS3, which inhibits the JAK/STAT3 pathway, by AFP-D55-SOCS3 not only could antagonize HCC therapeutic resistance to TRAIL and adenoviruses, but could also induce cell cycle arrest in HCC cell lines. SOCS3 could down-regulate Cyclin D1 and anti-apoptotic proteins such as XIAP, Survivin, Bcl-xL, and Mcl-1, which are responsible for the synergistic inhibitory effects of AFP-D55-SOCS3 and AFP-D55-TRAIL. Dual gene and double-regulated oncolytic adenoviruses may provide safety and excellent antitumor effects for liver cancer, which is the advantage of a cancer-targeting gene virotherapy strategy.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>alpha-Fetoproteins - genetics</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Cellular signal transduction</subject><subject>Cytopathogenic Effect, Viral</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Genetic aspects</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - toxicity</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Hep G2 Cells</subject><subject>Hepatoma</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Kaplan-Meier Estimate</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Oncolytic Virotherapy</subject><subject>Oncolytic Viruses - genetics</subject><subject>Physiological aspects</subject><subject>Promoter Regions, Genetic</subject><subject>Protein kinases</subject><subject>Suppressor of Cytokine Signaling Proteins - genetics</subject><subject>Suppressor of Cytokine Signaling Proteins - metabolism</subject><subject>TNF-Related Apoptosis-Inducing Ligand - genetics</subject><subject>TNF-Related Apoptosis-Inducing Ligand - metabolism</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Tumor Burden - genetics</subject><subject>Virus Replication</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-L1DAUx4so7rp68ywBES92zK-2ybGMq7swMDC7nkuavsxE2mRM0pW5-4ebcUZFECSHvDw-35cv71sULwleECzk-908LSjOL0rko-KSVFVTNpzSx7nGnJWYcXpRPIvxC8aEVXXztLighNWkkfiy-N7O2wlcsm6L0g5Qm8s0Tz6ga2NAJ-QNut-0tyvUH9DdennH0DebduiDn_sRyg1s51ElGNAG9qPV6uegtdN-PCSrUTuA8w82zBFZh25gr5LXMI5ZFNBSBW2dn9Tz4olRY4QX5_uq-Pzx-n55U67Wn26X7arUnMhUZscgsSC8kkCFAEqGQUihK8FY3TesoQPRQhJhDNOKNxqaXnOQNa8oMDawq-Ltae4--K8zxNRNNh7tKAd-jp3ElNWiquV_SSHzb6QhOJOvT-RWjdBZZ3wKSh_prqW1yEumDcnU4h9UPgNMVnsHxub-X4J3J4EOPsYAptsHO6lw6Ajujrl3OffumHuXc8_4q7PfuZ9g-A3_CjoDb86AilqNJiinbfzD8UrUjHL2A5ycs-U</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>WEI, Rui-Cheng</creator><creator>XIN CAO</creator><creator>GUI, Jing-Hua</creator><creator>ZHOU, Xiu-Mei</creator><creator>DAN ZHONG</creator><creator>YAN, Qiao-Lin</creator><creator>HUANG, Wei-Dan</creator><creator>QIAN, Qi-Jun</creator><creator>ZHAO, Feng-Li</creator><creator>LIU, Xin-Yuan</creator><general>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>7X8</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20110901</creationdate><title>Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma</title><author>WEI, Rui-Cheng ; XIN CAO ; GUI, Jing-Hua ; ZHOU, Xiu-Mei ; DAN ZHONG ; YAN, Qiao-Lin ; HUANG, Wei-Dan ; QIAN, Qi-Jun ; ZHAO, Feng-Li ; LIU, Xin-Yuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-179e9081459e288e21dd898c58336b7372d1c8918ff3ca47ce7bc4e96452e33d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenovirus</topic><topic>alpha-Fetoproteins - genetics</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Cellular signal transduction</topic><topic>Cytopathogenic Effect, Viral</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene therapy</topic><topic>Genetic aspects</topic><topic>Genetic Therapy</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Genetic Vectors - toxicity</topic><topic>Health aspects</topic><topic>Health. Pharmaceutical industry</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Hep G2 Cells</topic><topic>Hepatoma</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Kaplan-Meier Estimate</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Oncolytic Virotherapy</topic><topic>Oncolytic Viruses - genetics</topic><topic>Physiological aspects</topic><topic>Promoter Regions, Genetic</topic><topic>Protein kinases</topic><topic>Suppressor of Cytokine Signaling Proteins - genetics</topic><topic>Suppressor of Cytokine Signaling Proteins - metabolism</topic><topic>TNF-Related Apoptosis-Inducing Ligand - genetics</topic><topic>TNF-Related Apoptosis-Inducing Ligand - metabolism</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Tumor Burden - genetics</topic><topic>Virus Replication</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WEI, Rui-Cheng</creatorcontrib><creatorcontrib>XIN CAO</creatorcontrib><creatorcontrib>GUI, Jing-Hua</creatorcontrib><creatorcontrib>ZHOU, Xiu-Mei</creatorcontrib><creatorcontrib>DAN ZHONG</creatorcontrib><creatorcontrib>YAN, Qiao-Lin</creatorcontrib><creatorcontrib>HUANG, Wei-Dan</creatorcontrib><creatorcontrib>QIAN, Qi-Jun</creatorcontrib><creatorcontrib>ZHAO, Feng-Li</creatorcontrib><creatorcontrib>LIU, Xin-Yuan</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WEI, Rui-Cheng</au><au>XIN CAO</au><au>GUI, Jing-Hua</au><au>ZHOU, Xiu-Mei</au><au>DAN ZHONG</au><au>YAN, Qiao-Lin</au><au>HUANG, Wei-Dan</au><au>QIAN, Qi-Jun</au><au>ZHAO, Feng-Li</au><au>LIU, Xin-Yuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>22</volume><issue>9</issue><spage>1109</spage><epage>1119</epage><pages>1109-1119</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><coden>HGTHE3</coden><abstract>Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively. The combined treatment of AFP-D55-SOCS3 and AFP-D55-TRAIL (2:3 ratio) exhibited potent antitumor activity in AFP-positive HCC cell lines compared with any other treatment both in vitro and in vivo. Specific replication and low progeny yield in AFP-positive HCC cell lines rendered these double-regulated oncolytic adenoviruses remarkably safe. Our data demonstrated that restoration of SOCS3, which inhibits the JAK/STAT3 pathway, by AFP-D55-SOCS3 not only could antagonize HCC therapeutic resistance to TRAIL and adenoviruses, but could also induce cell cycle arrest in HCC cell lines. SOCS3 could down-regulate Cyclin D1 and anti-apoptotic proteins such as XIAP, Survivin, Bcl-xL, and Mcl-1, which are responsible for the synergistic inhibitory effects of AFP-D55-SOCS3 and AFP-D55-TRAIL. Dual gene and double-regulated oncolytic adenoviruses may provide safety and excellent antitumor effects for liver cancer, which is the advantage of a cancer-targeting gene virotherapy strategy.</abstract><cop>Larchmont, NY</cop><pub>Liebert</pub><pmid>21361790</pmid><doi>10.1089/hum.2010.219</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1043-0342 |
| ispartof | Human gene therapy, 2011-09, Vol.22 (9), p.1109-1119 |
| issn | 1043-0342 1557-7422 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_902368569 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adenoviridae - genetics Adenovirus alpha-Fetoproteins - genetics Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Apoptosis - genetics Applied cell therapy and gene therapy Biological and medical sciences Biotechnology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - therapy Care and treatment Cell Line, Tumor Cellular signal transduction Cytopathogenic Effect, Viral Female Fundamental and applied biological sciences. Psychology Gene Expression Gene therapy Genetic aspects Genetic Therapy Genetic Vectors - administration & dosage Genetic Vectors - toxicity Health aspects Health. Pharmaceutical industry HEK293 Cells HeLa Cells Hep G2 Cells Hepatoma HT29 Cells Humans Industrial applications and implications. Economical aspects Kaplan-Meier Estimate Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - therapy Male Medical sciences Mice Mice, Inbred BALB C Mice, Nude Oncolytic Virotherapy Oncolytic Viruses - genetics Physiological aspects Promoter Regions, Genetic Protein kinases Suppressor of Cytokine Signaling Proteins - genetics Suppressor of Cytokine Signaling Proteins - metabolism TNF-Related Apoptosis-Inducing Ligand - genetics TNF-Related Apoptosis-Inducing Ligand - metabolism Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tumor Burden - genetics Virus Replication Xenograft Model Antitumor Assays |
| title | Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T01%3A03%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Augmenting%20the%20Antitumor%20Effect%20of%20TRAIL%20by%20SOCS3%20with%20Double-Regulated%20Replicating%20Oncolytic%20Adenovirus%20in%20Hepatocellular%20Carcinoma&rft.jtitle=Human%20gene%20therapy&rft.au=WEI,%20Rui-Cheng&rft.date=2011-09-01&rft.volume=22&rft.issue=9&rft.spage=1109&rft.epage=1119&rft.pages=1109-1119&rft.issn=1043-0342&rft.eissn=1557-7422&rft.coden=HGTHE3&rft_id=info:doi/10.1089/hum.2010.219&rft_dat=%3Cgale_proqu%3EA268790271%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=893721710&rft_id=info:pmid/21361790&rft_galeid=A268790271&rfr_iscdi=true |