Subcutaneous Delivery of Nanoconjugated Doxorubicin and Cisplatin for Locally Advanced Breast Cancer Demonstrates Improved Efficacy and Decreased Toxicity at Lower Doses Than Standard Systemic Combination Therapy In Vivo
Identifieur interne : 003326 ( Pmc/Curation ); précédent : 003325; suivant : 003327Subcutaneous Delivery of Nanoconjugated Doxorubicin and Cisplatin for Locally Advanced Breast Cancer Demonstrates Improved Efficacy and Decreased Toxicity at Lower Doses Than Standard Systemic Combination Therapy In Vivo
Auteurs : Stephanie M. Cohen [États-Unis] ; Ridhwi Mukerji [États-Unis] ; Shuang Cai [États-Unis] ; Ivan Damjanov [États-Unis] ; M. Laird Forrest [États-Unis] ; Mark S. Cohen [États-Unis]Source :
- American journal of surgery [ 0002-9610 ] ; 2011.
Abstract
Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. We hypothesize that nanocarrier-conjugated doxorubicin and cisplatin will have improved tumor efficacy with decreased systemic toxicity over standard drugs, even at lower doses.
Female Nu/Nu mice were injected in the breast with human MDA-MB-468LN cells and treated with either standard or nanocarrier-conjugated combination therapy (doxorubicin+cisplatin) at 50% or 75% MTD, and monitored for efficacy and toxicity over 12-weeks.
Efficacy results for mice treated with HA-conjugated doxorubicin/cisplatin at 50% MTD include:[complete responses(CR)=5, partial responses(PR)=2, and stable disease(SD)=1]and for HA-conjugated dox/cis at 75% MTD:[CR=7,PR=1; all CR’s confirmed histologically]. In comparison, mice given standard dox/cis(50% MTD)demonstrated:[progressive disease(PD)=6, SD=1, and PR=1] and for standard dox/cis(75% MTD):[PD=5,SD=3; p<0.0001 on multivariate ANOVA]. At 75% MTD, standard drug-treated mice had significant weight loss compared to nanocarrier drug-treated mice(p<0.001).
Subcutaneous nanocarrier-delivery of doxorubicin and cisplatin demonstrated significantly improved efficacy with decreased toxicity compared to standard agent combination therapy at all doses tested achieving complete pathologic tumor response.
Url:
DOI: 10.1016/j.amjsurg.2011.06.027
PubMed: 21982998
PubMed Central: 5198781
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Cohen</name><affiliation wicri:level="2"><nlm:aff id="A1">University of Kansas Medical Center, Department of Surgery, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Surgery, Kansas City</wicri:cityArea></affiliation></author><author><name sortKey="Mukerji, Ridhwi" sort="Mukerji, Ridhwi" uniqKey="Mukerji R" first="Ridhwi" last="Mukerji">Ridhwi Mukerji</name><affiliation wicri:level="2"><nlm:aff id="A1">University of Kansas Medical Center, Department of Surgery, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Surgery, Kansas City</wicri:cityArea></affiliation></author><author><name sortKey="Cai, Shuang" sort="Cai, Shuang" uniqKey="Cai S" first="Shuang" last="Cai">Shuang Cai</name><affiliation wicri:level="2"><nlm:aff id="A2">University of Kansas, Department of Pharmaceutical Chemistry, Lawrence, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas, Department of Pharmaceutical Chemistry, Lawrence</wicri:cityArea></affiliation></author><author><name sortKey="Damjanov, Ivan" sort="Damjanov, Ivan" uniqKey="Damjanov I" first="Ivan" last="Damjanov">Ivan Damjanov</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Kansas Medical Center, Department of Pathology, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Pathology, Kansas City</wicri:cityArea></affiliation></author><author><name sortKey="Forrest, M Laird" sort="Forrest, M Laird" uniqKey="Forrest M" first="M. 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Cohen</name><affiliation wicri:level="2"><nlm:aff id="A1">University of Kansas Medical Center, Department of Surgery, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Surgery, Kansas City</wicri:cityArea></affiliation></author><author><name sortKey="Mukerji, Ridhwi" sort="Mukerji, Ridhwi" uniqKey="Mukerji R" first="Ridhwi" last="Mukerji">Ridhwi Mukerji</name><affiliation wicri:level="2"><nlm:aff id="A1">University of Kansas Medical Center, Department of Surgery, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Surgery, Kansas City</wicri:cityArea></affiliation></author><author><name sortKey="Cai, Shuang" sort="Cai, Shuang" uniqKey="Cai S" first="Shuang" last="Cai">Shuang Cai</name><affiliation wicri:level="2"><nlm:aff id="A2">University of Kansas, Department of Pharmaceutical Chemistry, Lawrence, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas, Department of Pharmaceutical Chemistry, Lawrence</wicri:cityArea></affiliation></author><author><name sortKey="Damjanov, Ivan" sort="Damjanov, Ivan" uniqKey="Damjanov I" first="Ivan" last="Damjanov">Ivan Damjanov</name><affiliation wicri:level="2"><nlm:aff id="A3">University of Kansas Medical Center, Department of Pathology, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Pathology, Kansas City</wicri:cityArea></affiliation></author><author><name sortKey="Forrest, M Laird" sort="Forrest, M Laird" uniqKey="Forrest M" first="M. Laird" last="Forrest">M. Laird Forrest</name><affiliation wicri:level="2"><nlm:aff id="A2">University of Kansas, Department of Pharmaceutical Chemistry, Lawrence, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas, Department of Pharmaceutical Chemistry, Lawrence</wicri:cityArea></affiliation></author><author><name sortKey="Cohen, Mark S" sort="Cohen, Mark S" uniqKey="Cohen M" first="Mark S." last="Cohen">Mark S. Cohen</name><affiliation wicri:level="2"><nlm:aff id="A1">University of Kansas Medical Center, Department of Surgery, Kansas City, KS</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kansas</region></placeName><wicri:cityArea>University of Kansas Medical Center, Department of Surgery, Kansas City</wicri:cityArea></affiliation></author></analytic><series><title level="j">American journal of surgery</title><idno type="ISSN">0002-9610</idno><idno type="eISSN">1879-1883</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. We hypothesize that nanocarrier-conjugated doxorubicin and cisplatin will have improved tumor efficacy with decreased systemic toxicity over standard drugs, even at lower doses.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Female Nu/Nu mice were injected in the breast with human MDA-MB-468LN cells and treated with either standard or nanocarrier-conjugated combination therapy (doxorubicin+cisplatin) at 50% or 75% MTD, and monitored for efficacy and toxicity over 12-weeks.</p></sec><sec id="S3"><title>Results</title><p id="P3">Efficacy results for mice treated with HA-conjugated doxorubicin/cisplatin at 50% MTD include:[complete responses(CR)=5, partial responses(PR)=2, and stable disease(SD)=1]and for HA-conjugated dox/cis at 75% MTD:[CR=7,PR=1; all CR’s confirmed histologically]. In comparison, mice given standard dox/cis(50% MTD)demonstrated:[progressive disease(PD)=6, SD=1, and PR=1] and for standard dox/cis(75% MTD):[PD=5,SD=3; p<0.0001 on multivariate ANOVA]. At 75% MTD, standard drug-treated mice had significant weight loss compared to nanocarrier drug-treated mice(p<0.001).</p></sec><sec id="S4"><title>Conclusion</title><p id="P4">Subcutaneous nanocarrier-delivery of doxorubicin and cisplatin demonstrated significantly improved efficacy with decreased toxicity compared to standard agent combination therapy at all doses tested achieving complete pathologic tumor response.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0370473</journal-id><journal-id journal-id-type="pubmed-jr-id">471</journal-id><journal-id journal-id-type="nlm-ta">Am J Surg</journal-id><journal-id journal-id-type="iso-abbrev">Am. J. Surg.</journal-id><journal-title-group><journal-title>American journal of surgery</journal-title></journal-title-group><issn pub-type="ppub">0002-9610</issn><issn pub-type="epub">1879-1883</issn></journal-meta><article-meta><article-id pub-id-type="pmid">21982998</article-id><article-id pub-id-type="pmc">5198781</article-id><article-id pub-id-type="doi">10.1016/j.amjsurg.2011.06.027</article-id><article-id pub-id-type="manuscript">NIHMS320864</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Subcutaneous Delivery of Nanoconjugated Doxorubicin and Cisplatin for Locally Advanced Breast Cancer Demonstrates Improved Efficacy and Decreased Toxicity at Lower Doses Than Standard Systemic Combination Therapy In Vivo</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Cohen</surname><given-names>Stephanie M.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Mukerji</surname><given-names>Ridhwi</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Cai</surname><given-names>Shuang</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Damjanov</surname><given-names>Ivan</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Forrest</surname><given-names>M. Laird</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Cohen</surname><given-names>Mark S.</given-names></name><degrees>MD, FACS</degrees><xref ref-type="aff" rid="A1">a</xref></contrib></contrib-group><aff id="A1"><label>a</label>University of Kansas Medical Center, Department of Surgery, Kansas City, KS</aff><aff id="A2"><label>b</label>University of Kansas, Department of Pharmaceutical Chemistry, Lawrence, KS</aff><aff id="A3"><label>c</label>University of Kansas Medical Center, Department of Pathology, Kansas City, KS</aff><author-notes><corresp id="cor1">Corresponding Author: Mark S. Cohen, MD, FACS, Associate Professor and Vice Chair for Research, University of Kansas Medical Center, Department of Surgery, Mail Stop 2005, 3901 Rainbow Blvd., Kansas City, KS 66160, Phone: (913) 588-6112, Fax: (913) 588-4593</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>25</day><month>12</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>08</day><month>10</month><year>2011</year></pub-date><pub-date pub-type="ppub"><month>12</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>12</month><year>2016</year></pub-date><volume>202</volume><issue>6</issue><fpage>646</fpage><lpage>653</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.amjsurg.2011.06.027</pmc-comment>
<abstract><sec id="S1"><title>Background</title><p id="P1">Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. We hypothesize that nanocarrier-conjugated doxorubicin and cisplatin will have improved tumor efficacy with decreased systemic toxicity over standard drugs, even at lower doses.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Female Nu/Nu mice were injected in the breast with human MDA-MB-468LN cells and treated with either standard or nanocarrier-conjugated combination therapy (doxorubicin+cisplatin) at 50% or 75% MTD, and monitored for efficacy and toxicity over 12-weeks.</p></sec><sec id="S3"><title>Results</title><p id="P3">Efficacy results for mice treated with HA-conjugated doxorubicin/cisplatin at 50% MTD include:[complete responses(CR)=5, partial responses(PR)=2, and stable disease(SD)=1]and for HA-conjugated dox/cis at 75% MTD:[CR=7,PR=1; all CR’s confirmed histologically]. In comparison, mice given standard dox/cis(50% MTD)demonstrated:[progressive disease(PD)=6, SD=1, and PR=1] and for standard dox/cis(75% MTD):[PD=5,SD=3; p<0.0001 on multivariate ANOVA]. At 75% MTD, standard drug-treated mice had significant weight loss compared to nanocarrier drug-treated mice(p<0.001).</p></sec><sec id="S4"><title>Conclusion</title><p id="P4">Subcutaneous nanocarrier-delivery of doxorubicin and cisplatin demonstrated significantly improved efficacy with decreased toxicity compared to standard agent combination therapy at all doses tested achieving complete pathologic tumor response.</p></sec></abstract><kwd-group><kwd>Nanocarriers</kwd><kwd>Drug-delivery</kwd><kwd>Combination chemotherapy</kwd><kwd>Hyaluronic acid</kwd><kwd>Breast cancer</kwd><kwd>Locoregional therapy</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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