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    Comparison of the cellular molecular stress responses after treatments used in bladder cancer.

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    Authors
    Shackley, David C
    Haylett, A
    Whitehurst, Colin
    Betts, C D
    O'Flynn, K
    Clarke, Noel W
    Moore, James V
    Affiliation
    CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Manchester, UK. Daveshackley@hotmail.com
    Issue Date
    2002-12
    
    Metadata
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    Abstract
    OBJECTIVE: To investigate the molecular stress responses related to the quality of recovery of normal tissue after various treatments for bladder cancer, i.e. hyperthermia, ionizing radiation, mitomycin-C and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). MATERIALS AND METHODS: The study focused particularly on intracellular fibroblast levels of heat-shock protein-47 (HSP47) and HSP72, which are associated with collagen metabolism and the development of tolerance to repeated treatment, respectively. Iso-effective treatment doses (50% clonogenic cell survival) of each method were delivered to a 3T6 murine fibroblast model. Intracellular extracts were analysed at 3, 6, 9, 12 and 24 h after treatment, using Western blot analysis to compare the levels of HSP47 and HSP72. Time-matched treatment and control groups were quantified by comparison with actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression using appropriate software. RESULTS: There were various changes in levels of HSP expression with treatment method; HSP47 levels were significantly higher after hyperthermia and radiation but not with mitomycin-C or ALA-PDT. HSP72 levels were significantly higher with all methods except ALA-PDT. CONCLUSIONS: Hyperthermia and ionizing radiation are associated with early increases in levels of HSP47 (a marker of collagen metabolism), in contrast to ALA-PDT and mitomycin-C. These findings are compatible with clinical findings where fibrosis/scarring is common with the first two but not the last two methods. In addition, all methods except ALA-PDT are associated with an increase in HSP 72 (a protein associated with cellular tolerance) and this may help to explain, at a cellular level, why resistance to repeated ALA-PDT treatments does not seem to occur.
    Citation
    Comparison of the cellular molecular stress responses after treatments used in bladder cancer. 2002, 90 (9):924-32 BJU Int.
    Journal
    BJU International
    URI
    http://hdl.handle.net/10541/81241
    PubMed ID
    12460358
    Type
    Article
    Language
    en
    ISSN
    1464-4096
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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