Induction of Apoptosis in Mesothelioma Cells by Antisurvivin Oligonucleotides
Malignant pleural mesothelioma is a rare and aggressive tumor characterized by rapid progression, late metastases, and poor prognosis. In this study, we investigated the expression of survivin, a member of the inhibitors of apoptosis protein gene family, in mesothelioma and an antisense oligonucleot...
Gespeichert in:
| Veröffentlicht in: | Molecular cancer therapeutics 2002-07, Vol.1 (9), p.687-694 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 694 |
|---|---|
| container_issue | 9 |
| container_start_page | 687 |
| container_title | Molecular cancer therapeutics |
| container_volume | 1 |
| creator | Xia, Chunyao Xu, Zhidong Yuan, Xiaocheng Uematsu, Kazutsugu You, Liang Li, Kai Li, Li McCormick, Frank Jablons, David M |
| description | Malignant pleural mesothelioma is a rare and aggressive tumor characterized by rapid progression, late metastases, and poor
prognosis. In this study, we investigated the expression of survivin, a member of the inhibitors of apoptosis protein gene family, in mesothelioma and an antisense oligonucleotide-based gene
therapy for mesothelioma using survivin as a target. Initially, we documented the expression of survivin in human mesothelioma cell lines and fresh tissues using reverse transcription-PCR and Western blot analysis. Our results
showed that survivin was overexpressed in 7 of 8 (87.5%) mesothelioma cell lines assayed and in all (12 of 12; 100%) freshly
resected mesothelioma tissues analyzed. To investigate the use of survivin as a therapeutic target on mesothelioma, we carried
out transfections with antisurvivin oligonucleotides to induce apoptosis in mesothelioma cell lines MS-1 and H28. Results
from cellular transfection and subsequent analysis using the flow cytometry demonstrated that antisurvivin oligonucleotides
induced significantly greater apoptosis rates in the survivin-positive mesothelioma cell line H28 (42.5%) as compared with
the control oligonucleotides (16.2%; P < 0.001). The survivin -negative cell line LRK1A ( survivin−/− ) did not apoptose with antisense oligonucleotides. Furthermore, time course evaluation by Western blot analysis showed that
survivin was inhibited by antisurvivin oligonucleotides within 12 h after transfection. Our results show, for the first time, that
survivin , an inhibitors of apoptosis protein family gene member, is highly overexpressed in malignant pleural mesothelioma. Down-regulation
of survivin by a targeted antisense oligonucleotide appears to be an effective gene therapy approach to the treatment of mesothelioma. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_72760022</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72760022</sourcerecordid><originalsourceid>FETCH-LOGICAL-h238t-4c0777d995ee5493c6e60ebeb4727fd53ea055716782451f8b588a867d8f16113</originalsourceid><addsrcrecordid>eNpFkEtLw0AYRQdRrFb_gszKXWAemUeWpfgotHSj62Ey-dKMJJk4k1T67w1acXXv4nC43At0QwXXmRY0v_zpIlNU8gW6TemDEKoLRq_RgrJcFVyKG7Tb9NXkRh96HGq8GsIwhuQT9j3eQQpjA60PncVraNuEyxNe9aNPUzz644zsW38I_eRaCKOvIN2hq9q2Ce7PuUTvz09v69dsu3_ZrFfbrGFcj1nuiFKqKgoBIPKCOwmSQAllrpiqK8HBEiHm4UqzXNBal0Jrq6WqdE0lpXyJHn-9QwyfE6TRdD65eaLtIUzJzBpJCGMz-HAGp7KDygzRdzaezN8B_6bGH5ovH8E42zuIERLY6BpDTWGkVvwbLOdlpg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72760022</pqid></control><display><type>article</type><title>Induction of Apoptosis in Mesothelioma Cells by Antisurvivin Oligonucleotides</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Association for Cancer Research</source><creator>Xia, Chunyao ; Xu, Zhidong ; Yuan, Xiaocheng ; Uematsu, Kazutsugu ; You, Liang ; Li, Kai ; Li, Li ; McCormick, Frank ; Jablons, David M</creator><creatorcontrib>Xia, Chunyao ; Xu, Zhidong ; Yuan, Xiaocheng ; Uematsu, Kazutsugu ; You, Liang ; Li, Kai ; Li, Li ; McCormick, Frank ; Jablons, David M</creatorcontrib><description>Malignant pleural mesothelioma is a rare and aggressive tumor characterized by rapid progression, late metastases, and poor
prognosis. In this study, we investigated the expression of survivin, a member of the inhibitors of apoptosis protein gene family, in mesothelioma and an antisense oligonucleotide-based gene
therapy for mesothelioma using survivin as a target. Initially, we documented the expression of survivin in human mesothelioma cell lines and fresh tissues using reverse transcription-PCR and Western blot analysis. Our results
showed that survivin was overexpressed in 7 of 8 (87.5%) mesothelioma cell lines assayed and in all (12 of 12; 100%) freshly
resected mesothelioma tissues analyzed. To investigate the use of survivin as a therapeutic target on mesothelioma, we carried
out transfections with antisurvivin oligonucleotides to induce apoptosis in mesothelioma cell lines MS-1 and H28. Results
from cellular transfection and subsequent analysis using the flow cytometry demonstrated that antisurvivin oligonucleotides
induced significantly greater apoptosis rates in the survivin-positive mesothelioma cell line H28 (42.5%) as compared with
the control oligonucleotides (16.2%; P < 0.001). The survivin -negative cell line LRK1A ( survivin−/− ) did not apoptose with antisense oligonucleotides. Furthermore, time course evaluation by Western blot analysis showed that
survivin was inhibited by antisurvivin oligonucleotides within 12 h after transfection. Our results show, for the first time, that
survivin , an inhibitors of apoptosis protein family gene member, is highly overexpressed in malignant pleural mesothelioma. Down-regulation
of survivin by a targeted antisense oligonucleotide appears to be an effective gene therapy approach to the treatment of mesothelioma.</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>PMID: 12479365</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Annexin A5 - pharmacology ; Apoptosis ; Blotting, Western ; Caspase 3 ; Caspases - metabolism ; Cell Division ; Cell Survival ; DNA, Complementary - metabolism ; Dose-Response Relationship, Drug ; Down-Regulation ; Flow Cytometry ; Genetic Therapy ; Humans ; Inhibitor of Apoptosis Proteins ; Mesothelioma - pathology ; Mesothelioma - therapy ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Microtubule-Associated Proteins - pharmacology ; Neoplasm Proteins ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides - pharmacology ; Oligonucleotides, Antisense - pharmacology ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Transfection ; Tumor Cells, Cultured</subject><ispartof>Molecular cancer therapeutics, 2002-07, Vol.1 (9), p.687-694</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12479365$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xia, Chunyao</creatorcontrib><creatorcontrib>Xu, Zhidong</creatorcontrib><creatorcontrib>Yuan, Xiaocheng</creatorcontrib><creatorcontrib>Uematsu, Kazutsugu</creatorcontrib><creatorcontrib>You, Liang</creatorcontrib><creatorcontrib>Li, Kai</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>McCormick, Frank</creatorcontrib><creatorcontrib>Jablons, David M</creatorcontrib><title>Induction of Apoptosis in Mesothelioma Cells by Antisurvivin Oligonucleotides</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>Malignant pleural mesothelioma is a rare and aggressive tumor characterized by rapid progression, late metastases, and poor
prognosis. In this study, we investigated the expression of survivin, a member of the inhibitors of apoptosis protein gene family, in mesothelioma and an antisense oligonucleotide-based gene
therapy for mesothelioma using survivin as a target. Initially, we documented the expression of survivin in human mesothelioma cell lines and fresh tissues using reverse transcription-PCR and Western blot analysis. Our results
showed that survivin was overexpressed in 7 of 8 (87.5%) mesothelioma cell lines assayed and in all (12 of 12; 100%) freshly
resected mesothelioma tissues analyzed. To investigate the use of survivin as a therapeutic target on mesothelioma, we carried
out transfections with antisurvivin oligonucleotides to induce apoptosis in mesothelioma cell lines MS-1 and H28. Results
from cellular transfection and subsequent analysis using the flow cytometry demonstrated that antisurvivin oligonucleotides
induced significantly greater apoptosis rates in the survivin-positive mesothelioma cell line H28 (42.5%) as compared with
the control oligonucleotides (16.2%; P < 0.001). The survivin -negative cell line LRK1A ( survivin−/− ) did not apoptose with antisense oligonucleotides. Furthermore, time course evaluation by Western blot analysis showed that
survivin was inhibited by antisurvivin oligonucleotides within 12 h after transfection. Our results show, for the first time, that
survivin , an inhibitors of apoptosis protein family gene member, is highly overexpressed in malignant pleural mesothelioma. Down-regulation
of survivin by a targeted antisense oligonucleotide appears to be an effective gene therapy approach to the treatment of mesothelioma.</description><subject>Annexin A5 - pharmacology</subject><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Cell Division</subject><subject>Cell Survival</subject><subject>DNA, Complementary - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Down-Regulation</subject><subject>Flow Cytometry</subject><subject>Genetic Therapy</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins</subject><subject>Mesothelioma - pathology</subject><subject>Mesothelioma - therapy</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Microtubule-Associated Proteins - pharmacology</subject><subject>Neoplasm Proteins</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oligonucleotides - pharmacology</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLw0AYRQdRrFb_gszKXWAemUeWpfgotHSj62Ey-dKMJJk4k1T67w1acXXv4nC43At0QwXXmRY0v_zpIlNU8gW6TemDEKoLRq_RgrJcFVyKG7Tb9NXkRh96HGq8GsIwhuQT9j3eQQpjA60PncVraNuEyxNe9aNPUzz644zsW38I_eRaCKOvIN2hq9q2Ce7PuUTvz09v69dsu3_ZrFfbrGFcj1nuiFKqKgoBIPKCOwmSQAllrpiqK8HBEiHm4UqzXNBal0Jrq6WqdE0lpXyJHn-9QwyfE6TRdD65eaLtIUzJzBpJCGMz-HAGp7KDygzRdzaezN8B_6bGH5ovH8E42zuIERLY6BpDTWGkVvwbLOdlpg</recordid><startdate>20020701</startdate><enddate>20020701</enddate><creator>Xia, Chunyao</creator><creator>Xu, Zhidong</creator><creator>Yuan, Xiaocheng</creator><creator>Uematsu, Kazutsugu</creator><creator>You, Liang</creator><creator>Li, Kai</creator><creator>Li, Li</creator><creator>McCormick, Frank</creator><creator>Jablons, David M</creator><general>American Association for Cancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20020701</creationdate><title>Induction of Apoptosis in Mesothelioma Cells by Antisurvivin Oligonucleotides</title><author>Xia, Chunyao ; Xu, Zhidong ; Yuan, Xiaocheng ; Uematsu, Kazutsugu ; You, Liang ; Li, Kai ; Li, Li ; McCormick, Frank ; Jablons, David M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h238t-4c0777d995ee5493c6e60ebeb4727fd53ea055716782451f8b588a867d8f16113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Annexin A5 - pharmacology</topic><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cell Division</topic><topic>Cell Survival</topic><topic>DNA, Complementary - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Down-Regulation</topic><topic>Flow Cytometry</topic><topic>Genetic Therapy</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins</topic><topic>Mesothelioma - pathology</topic><topic>Mesothelioma - therapy</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Microtubule-Associated Proteins - pharmacology</topic><topic>Neoplasm Proteins</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oligonucleotides - pharmacology</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xia, Chunyao</creatorcontrib><creatorcontrib>Xu, Zhidong</creatorcontrib><creatorcontrib>Yuan, Xiaocheng</creatorcontrib><creatorcontrib>Uematsu, Kazutsugu</creatorcontrib><creatorcontrib>You, Liang</creatorcontrib><creatorcontrib>Li, Kai</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>McCormick, Frank</creatorcontrib><creatorcontrib>Jablons, David M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xia, Chunyao</au><au>Xu, Zhidong</au><au>Yuan, Xiaocheng</au><au>Uematsu, Kazutsugu</au><au>You, Liang</au><au>Li, Kai</au><au>Li, Li</au><au>McCormick, Frank</au><au>Jablons, David M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of Apoptosis in Mesothelioma Cells by Antisurvivin Oligonucleotides</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2002-07-01</date><risdate>2002</risdate><volume>1</volume><issue>9</issue><spage>687</spage><epage>694</epage><pages>687-694</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>Malignant pleural mesothelioma is a rare and aggressive tumor characterized by rapid progression, late metastases, and poor
prognosis. In this study, we investigated the expression of survivin, a member of the inhibitors of apoptosis protein gene family, in mesothelioma and an antisense oligonucleotide-based gene
therapy for mesothelioma using survivin as a target. Initially, we documented the expression of survivin in human mesothelioma cell lines and fresh tissues using reverse transcription-PCR and Western blot analysis. Our results
showed that survivin was overexpressed in 7 of 8 (87.5%) mesothelioma cell lines assayed and in all (12 of 12; 100%) freshly
resected mesothelioma tissues analyzed. To investigate the use of survivin as a therapeutic target on mesothelioma, we carried
out transfections with antisurvivin oligonucleotides to induce apoptosis in mesothelioma cell lines MS-1 and H28. Results
from cellular transfection and subsequent analysis using the flow cytometry demonstrated that antisurvivin oligonucleotides
induced significantly greater apoptosis rates in the survivin-positive mesothelioma cell line H28 (42.5%) as compared with
the control oligonucleotides (16.2%; P < 0.001). The survivin -negative cell line LRK1A ( survivin−/− ) did not apoptose with antisense oligonucleotides. Furthermore, time course evaluation by Western blot analysis showed that
survivin was inhibited by antisurvivin oligonucleotides within 12 h after transfection. Our results show, for the first time, that
survivin , an inhibitors of apoptosis protein family gene member, is highly overexpressed in malignant pleural mesothelioma. Down-regulation
of survivin by a targeted antisense oligonucleotide appears to be an effective gene therapy approach to the treatment of mesothelioma.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>12479365</pmid><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-7163 |
| ispartof | Molecular cancer therapeutics, 2002-07, Vol.1 (9), p.687-694 |
| issn | 1535-7163 1538-8514 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72760022 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Annexin A5 - pharmacology Apoptosis Blotting, Western Caspase 3 Caspases - metabolism Cell Division Cell Survival DNA, Complementary - metabolism Dose-Response Relationship, Drug Down-Regulation Flow Cytometry Genetic Therapy Humans Inhibitor of Apoptosis Proteins Mesothelioma - pathology Mesothelioma - therapy Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Microtubule-Associated Proteins - pharmacology Neoplasm Proteins Oligonucleotide Array Sequence Analysis Oligonucleotides - pharmacology Oligonucleotides, Antisense - pharmacology Proto-Oncogene Proteins c-bcl-2 - metabolism Reverse Transcriptase Polymerase Chain Reaction Time Factors Transfection Tumor Cells, Cultured |
| title | Induction of Apoptosis in Mesothelioma Cells by Antisurvivin Oligonucleotides |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T06%3A06%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Induction%20of%20Apoptosis%20in%20Mesothelioma%20Cells%20by%20Antisurvivin%20Oligonucleotides&rft.jtitle=Molecular%20cancer%20therapeutics&rft.au=Xia,%20Chunyao&rft.date=2002-07-01&rft.volume=1&rft.issue=9&rft.spage=687&rft.epage=694&rft.pages=687-694&rft.issn=1535-7163&rft.eissn=1538-8514&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E72760022%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=72760022&rft_id=info:pmid/12479365&rfr_iscdi=true |