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    Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model

    Access Status
    Open access via publisher
    Authors
    Broadhead, M.
    Dass, Crispin
    Choong, P.
    Date
    2011
    Type
    Journal Article
    
    Metadata
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    Citation
    Broadhead, M. and Dass, C. and Choong, P. 2011. Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model. British Journal of Cancer. 105: pp. 1503-1511.
    Source Title
    British Journal of Cancer
    DOI
    10.1038/bjc.2011.410
    ISSN
    00070920
    URI
    http://hdl.handle.net/20.500.11937/19073
    Collection
    • Curtin Research Publications
    Abstract

    Background: Pigment epithelium-derived factor (PEDF) is an endogenous glycoprotein with a potential role as a therapeutic for osteosarcoma. Animal studies have demonstrated the biological effects of PEDF on osteosarcoma; however, these results are difficult to extrapolate for human use due to the chosen study design and drug delivery methods. Methods: In this study we have attempted to replicate the human presentation and treatment of osteosarcoma using a murine orthotopic model of osteosarcoma. The effects of PEDF on osteosarcoma cell lines were evaluated in vitro prior to animal experimentation. Orthotopic tumours were induced by intra-tibial injection of SaOS-2 osteosarcoma cells. Treatment with PEDF was delayed until after the macroscopic appearance of primary tumours. Pigment epithelium-derived factor was administered systemically via an implanted intraperitoneal micro-osmotic pump. Results: In vitro, PEDF inhibited proliferation, induced apoptosis and inhibited cell cycling of osteosarcoma cells. Pigment epithelium-derived factor promoted adhesion to Collagen I and inhibited invasion through Collagen I. In vivo, treatment with PEDF caused a reduction in both primary tumour volume and burden of pulmonary metastases. Systemic administration of PEDF did not cause toxic effects on normal tissues. Conclusion: Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma.

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      Broadhead, M.; Choong, P.; Dass, Crispin (2012)
      The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, ...
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      Alcantara, M.; Nemazannikova, N.; Elahy, M.; Dass, Crispin (2014)
      Objective: Pigment epithelium-derived factor (PEDF) has proven anti-osteosarcoma activity. However, the mechanism(s) underpinning its ability to reduce primary bone tumour (osteosarcoma) metastasis is unknown. Methods: ...
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      Alcantara, M.; Nemazannikova, N.; Elahy, Mina; Dass, Crispin (2014)
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