Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells
Identifieur interne : 001928 ( Istex/Corpus ); précédent : 001927; suivant : 001929Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells
Auteurs : Qinglei Gao ; Xiaoyuan Huang ; Duozhuang Tang ; Yang Cao ; Gang Chen ; Yunping Lu ; Liang Zhuang ; Shixuan Wang ; Gang Xu ; Jianfeng Zhou ; Ding MaSource :
- Apoptosis [ 1360-8185 ] ; 2006-10-01.
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Abstract
Abstract: The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.
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DOI: 10.1007/s10495-006-9421-4
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R. China</mods:affiliation></affiliation></author><author><name sortKey="Huang, Xiaoyuan" sort="Huang, Xiaoyuan" uniqKey="Huang X" first="Xiaoyuan" last="Huang">Xiaoyuan Huang</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Tang, Duozhuang" sort="Tang, Duozhuang" uniqKey="Tang D" first="Duozhuang" last="Tang">Duozhuang Tang</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Cao, Yang" sort="Cao, Yang" uniqKey="Cao Y" first="Yang" last="Cao">Yang Cao</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Chen, Gang" sort="Chen, Gang" uniqKey="Chen G" first="Gang" last="Chen">Gang Chen</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Lu, Yunping" sort="Lu, Yunping" uniqKey="Lu Y" first="Yunping" last="Lu">Yunping Lu</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Zhuang, Liang" sort="Zhuang, Liang" uniqKey="Zhuang L" first="Liang" last="Zhuang">Liang Zhuang</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Wang, Shixuan" sort="Wang, Shixuan" uniqKey="Wang S" first="Shixuan" last="Wang">Shixuan Wang</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Xu, Gang" sort="Xu, Gang" uniqKey="Xu G" first="Gang" last="Xu">Gang Xu</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation></author><author><name sortKey="Zhou, Jianfeng" sort="Zhou, Jianfeng" uniqKey="Zhou J" first="Jianfeng" last="Zhou">Jianfeng Zhou</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: jfzhou@tjh.tjmu.edu.cn</mods:affiliation></affiliation></author><author><name sortKey="Ma, Ding" sort="Ma, Ding" uniqKey="Ma D" first="Ding" last="Ma">Ding Ma</name><affiliation><mods:affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: dma@tjh.tjmu.edu.cn</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Apoptosis</title><title level="j" type="sub">Devoted to the Rapid Publication of Innovative Basic and Clinically-Oriented Investigations into Programmed Cell Death</title><title level="j" type="abbrev">Apoptosis</title><idno type="ISSN">1360-8185</idno><idno type="eISSN">1573-675X</idno><imprint><publisher>Kluwer Academic Publishers</publisher><pubPlace>Boston</pubPlace><date type="published" when="2006-10-01">2006-10-01</date><biblScope unit="volume">11</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1789">1789</biblScope><biblScope unit="page" to="1800">1800</biblScope></imprint><idno type="ISSN">1360-8185</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1360-8185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis</term><term>Cell cycle</term><term>Checkpoint kinase 1</term><term>Polo-like kinase 1</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Qinglei Gao</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Xiaoyuan Huang</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Duozhuang Tang</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Yang Cao</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Gang Chen</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Yunping Lu</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Liang Zhuang</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Shixuan Wang</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Gang Xu</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string></affiliations></json:item><json:item><name>Jianfeng Zhou</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string><json:string>E-mail: jfzhou@tjh.tjmu.edu.cn</json:string></affiliations></json:item><json:item><name>Ding Ma</name><affiliations><json:string>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</json:string><json:string>E-mail: dma@tjh.tjmu.edu.cn</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Checkpoint kinase 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Polo-like kinase 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Cell cycle</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Apoptosis</value></json:item></subject><articleId><json:string>9421</json:string><json:string>NO00009421</json:string></articleId><arkIstex>ark:/67375/VQC-1FVMFMT5-F</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.</abstract><qualityIndicators><score>9.832</score><pdfWordCount>7098</pdfWordCount><pdfCharCount>43535</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>12</pdfPageCount><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>false</refBibsNative><abstractWordCount>236</abstractWordCount><abstractCharCount>1646</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells</title><genre><json:string>research-article</json:string></genre><host><title>Apoptosis</title><language><json:string>unknown</json:string></language><publicationDate>2006</publicationDate><copyrightDate>2006</copyrightDate><issn><json:string>1360-8185</json:string></issn><eissn><json:string>1573-675X</json:string></eissn><journalId><json:string>10495</json:string></journalId><volume>11</volume><issue>10</issue><pages><first>1789</first><last>1800</last></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Cancer Research</value></json:item><json:item><value>Virology</value></json:item><json:item><value>Oncology</value></json:item><json:item><value>Biochemistry, general</value></json:item><json:item><value>Cell Biology</value></json:item></subject></host><ark><json:string>ark:/67375/VQC-1FVMFMT5-F</json:string></ark><publicationDate>2006</publicationDate><copyrightDate>2006</copyrightDate><doi><json:string>10.1007/s10495-006-9421-4</json:string></doi><id>285B94518A3F588C196E86E5ACDCF1C62B9610A1</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-1FVMFMT5-F/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-1FVMFMT5-F/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/VQC-1FVMFMT5-F/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">Kluwer Academic Publishers</publisher><pubPlace>Boston</pubPlace><availability><licence><p>Springer Science + Business Media, LLC, 2006</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</p></availability><date>2006</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note>Report</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells</title><author xml:id="author-0000"><persName><forename type="first">Qinglei</forename><surname>Gao</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Xiaoyuan</forename><surname>Huang</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Duozhuang</forename><surname>Tang</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Yang</forename><surname>Cao</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Gang</forename><surname>Chen</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Yunping</forename><surname>Lu</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Liang</forename><surname>Zhuang</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Shixuan</forename><surname>Wang</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Gang</forename><surname>Xu</surname></persName><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0009" corresp="yes"><persName><forename type="first">Jianfeng</forename><surname>Zhou</surname></persName><email>jfzhou@tjh.tjmu.edu.cn</email><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Ding</forename><surname>Ma</surname></persName><email>dma@tjh.tjmu.edu.cn</email><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation></author><idno type="istex">285B94518A3F588C196E86E5ACDCF1C62B9610A1</idno><idno type="ark">ark:/67375/VQC-1FVMFMT5-F</idno><idno type="DOI">10.1007/s10495-006-9421-4</idno><idno type="article-id">9421</idno><idno type="article-id">NO00009421</idno></analytic><monogr><title level="j">Apoptosis</title><title level="j" type="sub">Devoted to the Rapid Publication of Innovative Basic and Clinically-Oriented Investigations into Programmed Cell Death</title><title level="j" type="abbrev">Apoptosis</title><idno type="pISSN">1360-8185</idno><idno type="eISSN">1573-675X</idno><idno type="journal-ID">true</idno><idno type="journal-SPIN">APPT</idno><idno type="issue-article-count">15</idno><idno type="volume-issue-count">12</idno><imprint><publisher>Kluwer Academic Publishers</publisher><pubPlace>Boston</pubPlace><date type="published" when="2006-10-01"></date><biblScope unit="volume">11</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1789">1789</biblScope><biblScope unit="page" to="1800">1800</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Checkpoint kinase 1</term></item><item><term>Polo-like kinase 1</term></item><item><term>Cell cycle</term></item><item><term>Apoptosis</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Medicine & Public Health</head><item><term>Cancer Research</term></item><item><term>Virology</term></item><item><term>Oncology</term></item><item><term>Biochemistry, general</term></item><item><term>Cell Biology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-10-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-1FVMFMT5-F/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus springer-journals not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//Springer-Verlag//DTD A++ V2.4//EN" URI="http://devel.springer.de/A++/V2.4/DTD/A++V2.4.dtd" name="istex:docType"></istex:docType><istex:document><Publisher><PublisherInfo><PublisherName>Kluwer Academic Publishers</PublisherName><PublisherLocation>Boston</PublisherLocation></PublisherInfo><Journal><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>10495</JournalID><JournalPrintISSN>1360-8185</JournalPrintISSN><JournalElectronicISSN>1573-675X</JournalElectronicISSN><JournalSPIN>APPT</JournalSPIN><JournalTitle>Apoptosis</JournalTitle><JournalSubTitle>Devoted to the Rapid Publication of Innovative Basic and Clinically-Oriented Investigations into Programmed Cell Death</JournalSubTitle><JournalAbbreviatedTitle>Apoptosis</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Type="Primary">Medicine & Public Health</JournalSubject><JournalSubject Type="Secondary">Cancer Research</JournalSubject><JournalSubject Type="Secondary">Virology</JournalSubject><JournalSubject Type="Secondary">Oncology</JournalSubject><JournalSubject Type="Secondary">Biochemistry, general</JournalSubject><JournalSubject Type="Secondary">Cell Biology</JournalSubject></JournalSubjectGroup></JournalInfo><Volume><VolumeInfo TocLevels="0" VolumeType="Regular"><VolumeIDStart>11</VolumeIDStart><VolumeIDEnd>11</VolumeIDEnd><VolumeIssueCount>12</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular"><IssueInfo TocLevels="0"><IssueIDStart>10</IssueIDStart><IssueIDEnd>10</IssueIDEnd><IssueArticleCount>15</IssueArticleCount><IssueHistory><CoverDate><Year>2006</Year><Month>10</Month></CoverDate></IssueHistory><IssueCopyright><CopyrightHolderName>Springer Science + Business Media, LLC</CopyrightHolderName><CopyrightYear>2006</CopyrightYear></IssueCopyright></IssueInfo><Article ID="NO00009421"><ArticleInfo ArticleType="OriginalPaper" ContainsESM="No" Language="En" NumberingStyle="Unnumbered" TocLevels="0"><ArticleID>9421</ArticleID><ArticleDOI>10.1007/s10495-006-9421-4</ArticleDOI><ArticleSequenceNumber>10</ArticleSequenceNumber><ArticleTitle Language="En">Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells</ArticleTitle><ArticleCategory>Report</ArticleCategory><ArticleFirstPage>1789</ArticleFirstPage><ArticleLastPage>1800</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2006</Year><Month>1</Month><Day>1</Day></RegistrationDate><OnlineDate><Year>2006</Year><Month>8</Month><Day>21</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer Science + Business Media, LLC</CopyrightHolderName><CopyrightYear>2006</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Qinglei</GivenName><FamilyName>Gao</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Xiaoyuan</GivenName><FamilyName>Huang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Duozhuang</GivenName><FamilyName>Tang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Yang</GivenName><FamilyName>Cao</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Gang</GivenName><FamilyName>Chen</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Yunping</GivenName><FamilyName>Lu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Liang</GivenName><FamilyName>Zhuang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Shixuan</GivenName><FamilyName>Wang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Gang</GivenName><FamilyName>Xu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Jianfeng</GivenName><FamilyName>Zhou</FamilyName></AuthorName><Contact><Email>jfzhou@tjh.tjmu.edu.cn</Email></Contact></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Ding</GivenName><FamilyName>Ma</FamilyName></AuthorName><Contact><Email>dma@tjh.tjmu.edu.cn</Email></Contact></Author><Affiliation ID="Aff1"><OrgDivision>Cancer Biology Research Center</OrgDivision><OrgName>TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology</OrgName><OrgAddress><Street>1095 Jie-Fang Avenue, WuHan</Street><City>HuBei</City><Postcode>430030</Postcode><Country Code="CN">P. R. China</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En"><Heading>Abstract</Heading><Para>The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.</Para></Abstract><KeywordGroup Language="En"><Heading>Keywords</Heading><Keyword>Checkpoint kinase 1</Keyword><Keyword>Polo-like kinase 1</Keyword><Keyword>Cell cycle</Keyword><Keyword>Apoptosis</Keyword></KeywordGroup><ArticleNote Type="Dedication"><SimplePara>Qinglei Gao and Xiaoyuan Huang contributed equally to this work.</SimplePara></ArticleNote></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells</title></titleInfo><name type="personal"><namePart type="given">Qinglei</namePart><namePart type="family">Gao</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xiaoyuan</namePart><namePart type="family">Huang</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Duozhuang</namePart><namePart type="family">Tang</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yang</namePart><namePart type="family">Cao</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gang</namePart><namePart type="family">Chen</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yunping</namePart><namePart type="family">Lu</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liang</namePart><namePart type="family">Zhuang</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Shixuan</namePart><namePart type="family">Wang</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gang</namePart><namePart type="family">Xu</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Jianfeng</namePart><namePart type="family">Zhou</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><affiliation>E-mail: jfzhou@tjh.tjmu.edu.cn</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ding</namePart><namePart type="family">Ma</namePart><affiliation>Cancer Biology Research Center, TongJi Hospital, TongJi Medical College, Huazhong University of Science & Technology, 1095 Jie-Fang Avenue, WuHan, 430030, HuBei, P. R. China</affiliation><affiliation>E-mail: dma@tjh.tjmu.edu.cn</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Kluwer Academic Publishers</publisher><place><placeTerm type="text">Boston</placeTerm></place><dateIssued encoding="w3cdtf">2006-10-01</dateIssued><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.</abstract><note>Report</note><subject lang="en"><genre>Keywords</genre><topic>Checkpoint kinase 1</topic><topic>Polo-like kinase 1</topic><topic>Cell cycle</topic><topic>Apoptosis</topic></subject><relatedItem type="host"><titleInfo><title>Apoptosis</title><subTitle>Devoted to the Rapid Publication of Innovative Basic and Clinically-Oriented Investigations into Programmed Cell Death</subTitle></titleInfo><titleInfo type="abbreviated"><title>Apoptosis</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2006-10-01</dateIssued><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><subject><genre>Medicine & Public Health</genre><topic>Cancer Research</topic><topic>Virology</topic><topic>Oncology</topic><topic>Biochemistry, general</topic><topic>Cell Biology</topic></subject><identifier type="ISSN">1360-8185</identifier><identifier type="eISSN">1573-675X</identifier><identifier type="JournalID">10495</identifier><identifier type="JournalSPIN">APPT</identifier><identifier type="IssueArticleCount">15</identifier><identifier type="VolumeIssueCount">12</identifier><part><date>2006</date><detail type="volume"><number>11</number><caption>vol.</caption></detail><detail type="issue"><number>10</number><caption>no.</caption></detail><extent unit="pages"><start>1789</start><end>1800</end></extent></part><recordInfo><recordOrigin>Springer Science + Business Media, LLC, 2006</recordOrigin></recordInfo></relatedItem><identifier type="istex">285B94518A3F588C196E86E5ACDCF1C62B9610A1</identifier><identifier type="ark">ark:/67375/VQC-1FVMFMT5-F</identifier><identifier type="DOI">10.1007/s10495-006-9421-4</identifier><identifier type="ArticleID">9421</identifier><identifier type="ArticleID">NO00009421</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer Science + Business Media, LLC, 2006</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer Science + Business Media, LLC, 2006</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-1FVMFMT5-F/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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