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    Transferrin-Liposome-Mediated Systemic p53 Gene Therapy in Combination with Radiation Results in Regression of Human Head and Neck Cancer Xenografts

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    XuLiang_HGT_10(18)2941.pdf (1.093Mb)
    Issue Date
    1999-12-10
    Author
    Xu, Liang
    Pirollo, Kathleen F.
    Tang, Wen-Hua
    Rait, Antonina
    Chang, Esther H.
    Publisher
    Mary Ann Liebert
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    The use of cationic liposomes as nonviral vehicles for the delivery of therapeutic molecules is becoming increasingly prevalent in the field of gene therapy. We have previously demonstrated that the use of the transferrin ligand (Tf) to target a cationic liposome delivery system resulted in a significant increase in the transfection efficiency of the complex [Xu, L., Pirollo, K.F., and Chang, E.H. (1997). Hum. Gene Ther. 8, 467-475]. Delivery of wild-type (wt) p53 to a radiation-resistant squamous cell carcinoma of the head and neck (SCCHN) cell line via this ligand-targeted, liposome complex was also able to revert the radiation resistant phenotype of these cells in vitro. Here we optimized the Tf/liposome/DNA ratio of the complex (LipT) for maximum tumor cell targeting, even in the presence of serum. The efficient reestablishment of wtp53 function in these SCCHN tumor cells in vitro, via the LipT complex, restored the apoptotic pathway, resulting in a significant increase in radiation-induced apoptosis that was directly proportional to the level of exogenous wtp53 in the tumor cells. More significantly, intravenous administration of LipT-p53 markedly sensitized established SCCHN nude mouse xenograft tumors to radiotherapy. The combination of systemic LipT-p53 gene therapy and radiation resulted in complete tumor regression and inhibition of their recurrence even 6 months after the end of all treatment. These results indicate that this tumor-specific, ligand-liposome delivery system for p53 gene therapy, when used in concert with conventional radiotherapy, can provide a new and more effective means of cancer treatment.
    Description
    This is the published version, also available here: http://dx.doi.org/10.1089/10430349950016357.
    URI
    http://hdl.handle.net/1808/17358
    DOI
    https://doi.org/10.1089/10430349950016357
    Collections
    • Molecular Biosciences Scholarly Works [598]
    Citation
    Liang Xu, Kathleen F. Pirollo, Wen-Hua Tang, Antonina Rait, and Esther H. Chang. Human Gene Therapy. December 1999, 10(18): 2941-2952. http://dx.doi.org/10.1089/10430349950016357.

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    KU Libraries
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    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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