Author of

• 12418

  +

  P3.05 - Poster Session 3 - Preclinical Models of Therapeutics/Imaging (ID 159)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12437

    +

    P3.05-020 - Strategies for the prevention of mesothelioma in MexTAg mice (ID 3205)

    09:30 - 09:30  |  Author(s): A. Walsh
    • Abstract

    Background
    Current treatments for mesothelioma typically increase median survival by a matter of months. Progress in treatment has been hampered by lack of a suitable small animal model, which could guide clinical advances, given limited numbers of patients eligible for clinical trials. To this end we recently developed a transgenic mouse model of mesothelioma in which the viral oncogene, SV40TAg (TAg) is directed to mesothelial cells by use of the cell type specific mesothelin promoter. MexTAg mice develop mesothelioma rapidly and uniformly, but only following exposure to the natural carcinogen, asbestos. The model closely mimics the human disease and is thus ideal for both rapid analysis of novel therapeutic studies and for investigating factors that might act synergistically with asbestos to cause disease. Since all MexTAg mice develop mesothelioma following asbestos exposure the model is highly suitable for early intervention and cancer prevention studies. An effective cancer prevention strategy for the millions of people who have been exposed to asbestos could have enormous benefit worldwide. Epidemiological evidence indicates that supplementation with some dietary factors or use of common drugs such as statins and non-steroidal anti-inflammatory drugs is associated with a lower incidence of cancer.

    Methods
    not applicable

    Results
    We previously reported that dietary supplementation with a number of antioxidants did not alter the time to develop disease nor overall survival, despite the widely accepted hypothesis that asbestos catalyzed production of reactive oxygen and nitrogen species contribute to the development of this cancer. We have extended these studies to test whether vitamin D, non-steroidal anti-inflammatories, statins and some other candidate diets could alter the pattern of disease in the MexTAg model. Supplemented diets were provided at levels based on published data and began 2 weeks prior to asbestos exposure in order to maximize our chance of detecting a benefit. Preliminary data suggests a single agent or nutraceutical may not be enough to prevent the multiple pathways involved in tumorigenesis. This is somewhat supported by epidemiological data from the Wittenoom cohort of asbestos exposed workers and residents.

    Conclusion
    In conclusion, we think it is unlikely that antioxidants, anti-inflammatories or other nutrient-specific dietary supplements will moderate the rate of mesothelioma in asbestos exposed populations.