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    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

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    Issue Date
    2011-10-08
    Author
    Cohen, Stephanie M.
    Mukerji, Ridhwi
    Cai, Shuang
    Damjanov, Ivan
    Forrest, M. Laird
    Cohen, Mark S.
    Publisher
    Elsevier
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2011 Elsevier Inc. All rights reserved.
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    Abstract
    Background—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.

    Methods—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.

    Results—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).

    Conclusion—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.
    URI
    http://hdl.handle.net/1808/23237
    DOI
    https://doi.org/10.1016/j.amjsurg.2011.06.027
    Collections
    • Pharmaceutical Chemistry Scholarly Works [327]
    Citation
    Cohen, S. M., Mukerji, R., Cai, S., Damjanov, I., Forrest, M. L., & Cohen, M. S. (2011). 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. American Journal of Surgery, 202(6), 646–653. http://doi.org/10.1016/j.amjsurg.2011.06.027

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    KU Libraries
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    785-864-8983

    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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