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Home  /   Forum   /   BioPharma   /   Insmed, in de gaten houden

BioPharma« Terug naar discussie overzicht

Insmed, in de gaten houden

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20.047 Posts
Pagina: «« 1 ... 485 486 487 488 489 ... 1003 »» | Laatste | Omlaag ↓
  9. [verwijderd] 13 april 2006 16:35
    Van het Yahoo forum

    Yahoo! Message Boards: INSM Add to My Yahoo


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    < Previous | Next > [ First | Last | Msg List ] Msg #: Reply
    Recommend this Post - This post has 3 recommendations Ignore this User | Report Abuse
    Re: Implications for INSM-rIGFBP-3 find
    by: skip1cf (40/Beverly Hills, CA)
    Long-Term Sentiment: Strong Buy 04/13/06 09:33 am
    Msg: 86141 of 86154

    ...Great pick; pay also attention to last page!

    Recombinant human insulin-like growth factor binding protein-3 (rhIGFBP-3) as a potential therapeutic agent for the treatment of Herceptin-resistant breast cancer.
    Lori Jerome1, Qingnan Yu1, Sylvie Belanger1, Laura Shiry2, Mark Pegram3 and Brian Leyland-Jones1. 1Oncology, McGill University, Montreal, QC, Canada; 2Preclinical
    Development, Insmed Incorporated, Richmond, VA and 3Medicine – Hematology and Oncology, UCLA, Los Angeles, CA.
    #270
    INTRODUCTION
    •Human epidermal growth factor receptor-2 (HER-2/ erbB2) is a 185kDa transmembrane protein with tyrosine kinase activity.
    •HER-2 is overexpressed in 20-30% of human breast cancers and is associated with enhanced tumor aggressiveness and a high risk of relapse and death.
    •Herceptin (Trastuzumab) is a humanized monoclonal antibody that targets HER-2 and has demonstrated clinical activity against HER-2-overexpressing breast tumors.
    •Resistance to Herceptin is common and evidence suggests that the insulin-like growth factor receptor (IGF-IR) may be involved.
    •Preliminary data have shown that interference with IGFIR signaling via co-treatment with recombinant human IGF-binding protein-3 (rhIGFBP-3) restores the growthsuppressive effect of Herceptin in otherwise resistant breast cancer cell lines (Lu et al. 2001JNCI 93:1852-7).
    •This study was designed to further explore the ability of rhIGFBP-3 to sensitize breast tumors to Herceptin using cell lines with enforced (transfected; MCF-7/HER2-18
    and SKBR3/IGF-IR) or acquired (BT474/HerR) drug resistance.
    •HER-2-overexpressing breast cancer cell lines were exposed to a range of Herceptin and/or rhIGFBP-3 concentrations in the presence of 10% FBS for 72 hours and cell survival was measured by MTT assay.
    •Total and activated IGF-IR and HER-2 levels were determined by Western blotting using antibodies from Santa Cruz (anti-IGF-IRβ C20), Upstate (antierbB2/ HER-2 and anti-phospho-erbB2/HER-2 Y1248) and Cell Signaling (anti-phospho-IGF-IR). Anti-β-tubulin (Sigma) and anti-PTP1D/SHP2 (Transduction Laboratories) served as loading controls.
    METHODS
    1. Resistance to Herceptin correlates with increased IGF-IR levels in transfected breast cancer cells (MCF- 7/HER2-18 and SKBR3/IGF-IR) and in a cell line with acquired drug resistance (BT474/HerR).
    2. Treatment with rhIGFBP-3 markedly inhibited growth of Herceptin-resistant breast cancer cells in a dosedependent manner (Fig 2).
    3. When combined with Herceptin, rhIGFBP-3 elicited a strong dose-dependent increase in Herceptin sensitivity of SKBR3/IGF-IR and BT474/HerR (Fig 3).
    4. The degree of inhibition of IGF-I-induced IGF-IR phosphorylation by rhIGFBP-3 (Fig 4) correlated with the extent of Herceptin sensitization (Fig 3).
    CONCLUSIONS
    rhIGFBP-3 displayed potent single-agent and combinatorial activity with Herceptin in HER-2- overexpressing breast carcinoma cells.
    Ongoing in vivo experiments are directed at evaluating the anti-tumor activity of rhIGFBP-3 with models incorporating these cell lines.
    ACKNOWLEDGEMENTS
    SKBR3, SKBR3/IGF-IR and MCF-7/HER2-18 were generously provided by Dr. Michael Pollak, Department of Oncology, Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
    www.insmed.com/SABCS%2003.pdf

    Long Scf



    Posted as a reply to: Msg 86140 by climbergeorge70

20.047 Posts
Pagina: «« 1 ... 485 486 487 488 489 ... 1003 »» | Laatste |Omhoog ↑

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