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Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma.

Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Research Abstract Details 

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  • Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Abstract Text:

    zeng bian zhuZeng Bian Zhu,yabing chenYabing Chen,sharmila k makhijaSharmila K Makhija,baogen luBaogen Lu,minghui wangMinghui Wang,angel a riveraAngel A Rivera,masato yamamotoMasato Yamamoto,shuyi wangShuyi Wang,gene p siegalGene P Siegal,david t curielDavid T Curiel,jay m mcdonaldJay M McDonald,

    Cholangiocarcinoma is a highly malignant neoplasm with no effective treatment. Conditionally replicative adenoviruses (CRAds) represent a promising new modality for the treatment of cancer in general. A key contribution in this regard was the introduction of tumor-selective viral replication for amplification of the initial inoculum in the neoplastic cell population. Under ideal conditions following cellular infection, the viruses replicate selectively in the infected tumor cells and kill the cells by cytolysis, leaving normal cells unaffected. However, to date there have been two limitations to the clinical application of these CRAd agents, i.e. poor viral infectivity and tumor specificity. Here we report the construction of three new CRAd agents, CRAd-S.RGD, CRAd-S.F5/3 and CRAd-S.pk7, in which the tumor specificity is regulated by a tumor-specific promoter, the survivin promoter, and the viral infectivity is enhanced by incorporating a capsid modification (RGD, F5/3 or pk7) in the adenovirus fiber region. These CRAd agents effectively target cholangiocarcinoma cells, induce strong cytoxicity in these cells in vitro and inhibit tumor growth in a murine xenograft model in vivo. In addition, the survivin promoter has extremely low activity both in the non-transformed cell line, HMEC, and in human liver tissue. Our results suggest that the survivin-based CRAds are promising agents for targeting cholangiocarcinoma with low host toxicity. Such results should provide important insights into the identification of novel therapeutic strategies for cholangiocarcinoma.

    Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Publishing Authors By Initials

    zb zhuZB Zhu,y chenY Chen,sk makhijaSK Makhija,b luB Lu,m wangM Wang,aa riveraAA Rivera,m yamamotoM Yamamoto,s wangS Wang,gp siegalGP Siegal,dt curielDT Curiel,jm mcdonaldJM McDonald,

    For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

    PUBMED ID PMID:

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    Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: International journal of oncology

    VOLUME: 29

    Page Numbers: 1319-29

    Journal Abbreviation: Int. J. Oncol.

    ISSN: 1019-6439

    DAY: 3

    MONTH: Nov

    YEAR: 2006

    Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 9306042

    Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Keywords Mesh Terms:

    KEYWORDS: Xenograft Model Antitumor Assays

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma. Information

    Substance Name: Neoplasm Proteins

    Registry Number: 0

    Grant and Affiliation Information for Survivin promoter-based conditionally replicative adenoviruses target cholangiocarcinoma.

    AFFILIATION: Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL 35291, USA.

    Country: Greece

    Greece Research PublicationGreece Research Publication

    AGENCY: United States NIDDK

    GRANT: R01 DK063615-01

    ACRONYM: DK

    MEDLINETA: Int J Oncol

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