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KREFTSATS-Særutlysning kreftmidler, historikk

Retinoids, antioxidants and cancer

Tildelt: kr 7,0 mill.





2004 - 2007


Retinol and its metabolites (vitamin A, retinoids) orchestrates proliferation and differentiation through its nuclear retinoic acid receptors. Antioxidants have also recently been implied in regulation of cell signalling and gene transcription. There exis t convincing evidence that diets high in vegetables and fruit decrease the risk of cancer in a number of organs. Provitamin A carotenoids and antioxidants in fruits and vegetables are strong candidates for explaining this anti-cancer effect. Retinoids a nd antioxidants efficiently regulates gene expression in cell cultures, but much less is known about their role in living organism. We have therefore develop techniques for assessing their roles in intact experimental animals. These transgenic reporter m ice allows non-invasive imaging of gene expression in living mice. We will now develop these reporter mice further and study role of retinoic acid and antioxidants on gene expression during tumor development. We will also develop caspase reportermice sin ce retinoids and antioxidants modulate these important activators of apoptosis in vitro. In collaboration with scientists at the Norwegian Radium Hospital we study gene profiling of oxidative stress-related genes in patients with head and neck squamous cell carcinoma (HNSCC) and the association between plasma redox status and survival in patients with HNSCC since a pilot study suggested a strong association between HNSCC survival and plasma total glutathione and carotenoids. We will also test the abilit y of dietary antioxidants to improve oxidatice stress in a group of smoking middle-aged men. We have performed total antioxidant analysis of several thousand foods. By using this antioxidannt table we are now testing association between dietary antioxida nts and cancer risk in three large epidemiological studies (Nurses' Health Study, Health Professionals' Follow-up Study, Iowa Women Health Study) in collaboration with Walter Willett and David Jacobs.


KREFTSATS-Særutlysning kreftmidler, historikk