Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer
The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic ex...
Gespeichert in:
| Veröffentlicht in: | Molecular cancer therapeutics 2014-07, Vol.13 (7), p.1750-1757 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1757 |
|---|---|
| container_issue | 7 |
| container_start_page | 1750 |
| container_title | Molecular cancer therapeutics |
| container_volume | 13 |
| creator | Gharpure, Kshipra M Chu, Kevin S Bowerman, Charles J Miyake, Takahito Pradeep, Sunila Mangala, Selanere L Han, Hee-Dong Rupaimoole, Rajesha Armaiz-Pena, Guillermo N Rahhal, Tojan B Wu, Sherry Y Luft, J Christopher Napier, Mary E Lopez-Berestein, Gabriel DeSimone, Joseph M Sood, Anil K |
| description | The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer. |
| doi_str_mv | 10.1158/1535-7163.MCT-13-0930 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4090269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>24755199</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-ed84f4d5e2677d1418c7b5fff467ba106dff912ad524499cbbeacfea4e5cd3453</originalsourceid><addsrcrecordid>eNpVkV9r2zAUxcXoWLtuH2FFX8Cpri3Z1sughHYJ9M8o6ctehCxdJSqOFCQntN9-drOV7emKq3N-F84h5BuwGYBoL0FUomigrmZ381UBVcFkxT6Qs3HfFq0AfvL2PmpOyeecnxmDVpbwiZyWvBECpDwj6Q6HFEPcekNtNDjoF-ypD_Tn4_J-RYMOcafT4E2Pmepg6fWvRUmz7zEYH9Z0ow9I82vAtPZ5lI2awQ_7bUwUnUMzTKx40MnrQI0OBtMX8tHpPuPXP_OcPN1cr-aL4vbhx3J-dVsYDjAUaFvuuBVY1k1jgUNrmk4453jddBpYbZ2TUGorSs6lNF2H2jjUHIWxFRfVOfl-5O723RatwTAk3atd8ludXlXUXv3_E_xGreNBcSZZWcsRII4Ak2LOCd27F5iaSlBTwGoKWI0lKKjUVMLou_j38Lvrb-rVb7kdh2Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Gharpure, Kshipra M ; Chu, Kevin S ; Bowerman, Charles J ; Miyake, Takahito ; Pradeep, Sunila ; Mangala, Selanere L ; Han, Hee-Dong ; Rupaimoole, Rajesha ; Armaiz-Pena, Guillermo N ; Rahhal, Tojan B ; Wu, Sherry Y ; Luft, J Christopher ; Napier, Mary E ; Lopez-Berestein, Gabriel ; DeSimone, Joseph M ; Sood, Anil K</creator><creatorcontrib>Gharpure, Kshipra M ; Chu, Kevin S ; Bowerman, Charles J ; Miyake, Takahito ; Pradeep, Sunila ; Mangala, Selanere L ; Han, Hee-Dong ; Rupaimoole, Rajesha ; Armaiz-Pena, Guillermo N ; Rahhal, Tojan B ; Wu, Sherry Y ; Luft, J Christopher ; Napier, Mary E ; Lopez-Berestein, Gabriel ; DeSimone, Joseph M ; Sood, Anil K</creatorcontrib><description>The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer.</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>DOI: 10.1158/1535-7163.MCT-13-0930</identifier><identifier>PMID: 24755199</identifier><language>eng</language><publisher>United States</publisher><subject>Administration, Metronomic ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - chemistry ; Cell Line, Tumor ; Enhancer of Zeste Homolog 2 Protein ; Female ; Gene Silencing - drug effects ; Humans ; Mice ; Mice, Nude ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Polycomb Repressive Complex 2 - antagonists & inhibitors ; Polycomb Repressive Complex 2 - genetics ; Polycomb Repressive Complex 2 - metabolism ; Randomized Controlled Trials as Topic ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - genetics ; Taxoids - administration & dosage ; Taxoids - chemistry</subject><ispartof>Molecular cancer therapeutics, 2014-07, Vol.13 (7), p.1750-1757</ispartof><rights>2014 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-ed84f4d5e2677d1418c7b5fff467ba106dff912ad524499cbbeacfea4e5cd3453</citedby><cites>FETCH-LOGICAL-c411t-ed84f4d5e2677d1418c7b5fff467ba106dff912ad524499cbbeacfea4e5cd3453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3354,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24755199$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gharpure, Kshipra M</creatorcontrib><creatorcontrib>Chu, Kevin S</creatorcontrib><creatorcontrib>Bowerman, Charles J</creatorcontrib><creatorcontrib>Miyake, Takahito</creatorcontrib><creatorcontrib>Pradeep, Sunila</creatorcontrib><creatorcontrib>Mangala, Selanere L</creatorcontrib><creatorcontrib>Han, Hee-Dong</creatorcontrib><creatorcontrib>Rupaimoole, Rajesha</creatorcontrib><creatorcontrib>Armaiz-Pena, Guillermo N</creatorcontrib><creatorcontrib>Rahhal, Tojan B</creatorcontrib><creatorcontrib>Wu, Sherry Y</creatorcontrib><creatorcontrib>Luft, J Christopher</creatorcontrib><creatorcontrib>Napier, Mary E</creatorcontrib><creatorcontrib>Lopez-Berestein, Gabriel</creatorcontrib><creatorcontrib>DeSimone, Joseph M</creatorcontrib><creatorcontrib>Sood, Anil K</creatorcontrib><title>Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer.</description><subject>Administration, Metronomic</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Cell Line, Tumor</subject><subject>Enhancer of Zeste Homolog 2 Protein</subject><subject>Female</subject><subject>Gene Silencing - drug effects</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Polycomb Repressive Complex 2 - antagonists & inhibitors</subject><subject>Polycomb Repressive Complex 2 - genetics</subject><subject>Polycomb Repressive Complex 2 - metabolism</subject><subject>Randomized Controlled Trials as Topic</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>Taxoids - administration & dosage</subject><subject>Taxoids - chemistry</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV9r2zAUxcXoWLtuH2FFX8Cpri3Z1sughHYJ9M8o6ctehCxdJSqOFCQntN9-drOV7emKq3N-F84h5BuwGYBoL0FUomigrmZ381UBVcFkxT6Qs3HfFq0AfvL2PmpOyeecnxmDVpbwiZyWvBECpDwj6Q6HFEPcekNtNDjoF-ypD_Tn4_J-RYMOcafT4E2Pmepg6fWvRUmz7zEYH9Z0ow9I82vAtPZ5lI2awQ_7bUwUnUMzTKx40MnrQI0OBtMX8tHpPuPXP_OcPN1cr-aL4vbhx3J-dVsYDjAUaFvuuBVY1k1jgUNrmk4453jddBpYbZ2TUGorSs6lNF2H2jjUHIWxFRfVOfl-5O723RatwTAk3atd8ludXlXUXv3_E_xGreNBcSZZWcsRII4Ak2LOCd27F5iaSlBTwGoKWI0lKKjUVMLou_j38Lvrb-rVb7kdh2Q</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Gharpure, Kshipra M</creator><creator>Chu, Kevin S</creator><creator>Bowerman, Charles J</creator><creator>Miyake, Takahito</creator><creator>Pradeep, Sunila</creator><creator>Mangala, Selanere L</creator><creator>Han, Hee-Dong</creator><creator>Rupaimoole, Rajesha</creator><creator>Armaiz-Pena, Guillermo N</creator><creator>Rahhal, Tojan B</creator><creator>Wu, Sherry Y</creator><creator>Luft, J Christopher</creator><creator>Napier, Mary E</creator><creator>Lopez-Berestein, Gabriel</creator><creator>DeSimone, Joseph M</creator><creator>Sood, Anil K</creator><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>5PM</scope></search><sort><creationdate>20140701</creationdate><title>Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer</title><author>Gharpure, Kshipra M ; Chu, Kevin S ; Bowerman, Charles J ; Miyake, Takahito ; Pradeep, Sunila ; Mangala, Selanere L ; Han, Hee-Dong ; Rupaimoole, Rajesha ; Armaiz-Pena, Guillermo N ; Rahhal, Tojan B ; Wu, Sherry Y ; Luft, J Christopher ; Napier, Mary E ; Lopez-Berestein, Gabriel ; DeSimone, Joseph M ; Sood, Anil K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-ed84f4d5e2677d1418c7b5fff467ba106dff912ad524499cbbeacfea4e5cd3453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Administration, Metronomic</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Cell Line, Tumor</topic><topic>Enhancer of Zeste Homolog 2 Protein</topic><topic>Female</topic><topic>Gene Silencing - drug effects</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Polycomb Repressive Complex 2 - antagonists & inhibitors</topic><topic>Polycomb Repressive Complex 2 - genetics</topic><topic>Polycomb Repressive Complex 2 - metabolism</topic><topic>Randomized Controlled Trials as Topic</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>Taxoids - administration & dosage</topic><topic>Taxoids - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gharpure, Kshipra M</creatorcontrib><creatorcontrib>Chu, Kevin S</creatorcontrib><creatorcontrib>Bowerman, Charles J</creatorcontrib><creatorcontrib>Miyake, Takahito</creatorcontrib><creatorcontrib>Pradeep, Sunila</creatorcontrib><creatorcontrib>Mangala, Selanere L</creatorcontrib><creatorcontrib>Han, Hee-Dong</creatorcontrib><creatorcontrib>Rupaimoole, Rajesha</creatorcontrib><creatorcontrib>Armaiz-Pena, Guillermo N</creatorcontrib><creatorcontrib>Rahhal, Tojan B</creatorcontrib><creatorcontrib>Wu, Sherry Y</creatorcontrib><creatorcontrib>Luft, J Christopher</creatorcontrib><creatorcontrib>Napier, Mary E</creatorcontrib><creatorcontrib>Lopez-Berestein, Gabriel</creatorcontrib><creatorcontrib>DeSimone, Joseph M</creatorcontrib><creatorcontrib>Sood, Anil K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gharpure, Kshipra M</au><au>Chu, Kevin S</au><au>Bowerman, Charles J</au><au>Miyake, Takahito</au><au>Pradeep, Sunila</au><au>Mangala, Selanere L</au><au>Han, Hee-Dong</au><au>Rupaimoole, Rajesha</au><au>Armaiz-Pena, Guillermo N</au><au>Rahhal, Tojan B</au><au>Wu, Sherry Y</au><au>Luft, J Christopher</au><au>Napier, Mary E</au><au>Lopez-Berestein, Gabriel</au><au>DeSimone, Joseph M</au><au>Sood, Anil K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>13</volume><issue>7</issue><spage>1750</spage><epage>1757</epage><pages>1750-1757</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer.</abstract><cop>United States</cop><pmid>24755199</pmid><doi>10.1158/1535-7163.MCT-13-0930</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-7163 |
| ispartof | Molecular cancer therapeutics, 2014-07, Vol.13 (7), p.1750-1757 |
| issn | 1535-7163 1538-8514 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4090269 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Administration, Metronomic Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - chemistry Cell Line, Tumor Enhancer of Zeste Homolog 2 Protein Female Gene Silencing - drug effects Humans Mice Mice, Nude Nanoparticles - administration & dosage Nanoparticles - chemistry Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Polycomb Repressive Complex 2 - antagonists & inhibitors Polycomb Repressive Complex 2 - genetics Polycomb Repressive Complex 2 - metabolism Randomized Controlled Trials as Topic RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics Taxoids - administration & dosage Taxoids - chemistry |
| title | Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T11%3A32%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Metronomic%20docetaxel%20in%20PRINT%20nanoparticles%20and%20EZH2%20silencing%20have%20synergistic%20antitumor%20effect%20in%20ovarian%20cancer&rft.jtitle=Molecular%20cancer%20therapeutics&rft.au=Gharpure,%20Kshipra%20M&rft.date=2014-07-01&rft.volume=13&rft.issue=7&rft.spage=1750&rft.epage=1757&rft.pages=1750-1757&rft.issn=1535-7163&rft.eissn=1538-8514&rft_id=info:doi/10.1158/1535-7163.MCT-13-0930&rft_dat=%3Cpubmed_cross%3E24755199%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/24755199&rfr_iscdi=true |