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    Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation.

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    Authors
    Chan, K C
    Knox, W F
    Gandhi, A
    Slamon, D J
    Potten, Christopher S
    Bundred, Nigel J
    Affiliation
    Department of Surgery, University Hospital of South Manchester, Manchester, UK.
    Issue Date
    2001-03
    
    Metadata
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    Abstract
    BACKGROUND: Ductal carcinoma in situ (DCIS) expresses c-erbB-2 receptor and epidermal growth factor receptor (EGFR). The aim of this study was to determine whether blocking of c-erbB-2 receptor with a humanized monoclonal antibody, 4D5 (HerceptinTM), or of EGFR with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (IressaTM), would decrease epithelial proliferation in DCIS. METHODS: DCIS tissue from 18 women undergoing surgery was implanted into 16 to 20 athymic nude mice per experiment (eight xenografts per mouse). Treatment commenced 2 weeks after implantation and consisted either of twice-weekly intraperitoneal injections of 4D5 10 mg/kg or of daily gavage with ZD1839 at 100-200 mg/kg for 14 days; appropriate controls were included. Xenografts were removed on days 14, 21 and 28. Proliferation was assessed by counting 1000 epithelial cells after Ki67 immuno- staining. RESULTS: ZD1839 inhibited proliferation compared with that in controls after 14 days (P < 0.01), whereas 4D5 did not. CONCLUSION: Proliferation in DCIS was decreased by EGFR tyrosine kinase inhibition but not by c-erbB-2 receptor blockade. ZD1839, an orally active and selective EGFR-TKI, has potential as adjuvant therapy in DCIS.
    Citation
    Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation. 2001, 88 (3):412-8 Br J Surg
    Journal
    The British Journal of Surgery
    URI
    http://hdl.handle.net/10541/85562
    DOI
    10.1046/j.1365-2168.2001.01686.x
    PubMed ID
    11260109
    Type
    Article
    Language
    en
    ISSN
    0007-1323
    ae974a485f413a2113503eed53cd6c53
    10.1046/j.1365-2168.2001.01686.x
    Scopus Count
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    All Paterson Institute for Cancer Research

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