Protein-bound polysaccharide K (PSK), a hot water extract from the fruiting body and mycelia of the Coriolus versicolor (CV) mushroom, has significant adjuvant activity in combination with oral fluorouracil chemotherapy for the treatment of gastric cancer and is approved for this indication in Japan. Recently, hot water extracts from the CV mushroom have been used as nutritional supplements by cancer patients in the US. Given the extensive use of these supplements, comparative studies into the bioactivity of the clinical (PSK) and nutritional supplement (VPS) preparations are warranted and we propose to compare their tumor preventative, and therapeutic activities, as well as extend our understanding of their mechanism of action based on immune augmentation. This proposal will address the hypothesis that the oral administration of PSK and VPS results in immunomodulatory activity and preventative and therapeutic activity in mice for colorectal cancer. This hypothesis will be tested using two autochthonous tumor models: 1,2-dimethylhydrazine (DMH) induced colorectal tumors and the Apcmin transgenic model of gastrointestinal polyps and adenomas. Our long-term objective is to initiate clinical studies in colorectal cancer, if warranted by these studies, using VPS and the immune surrogates identified by this proposal to support the phase I dose-finding protocols.
Three Specific Aims are proposed to test our hypothesis: 1: Determine and compare the preventative and therapeutic activity of PSK and VPS for DMH induced preneoplastic lesions, adenomas and adenocarcinomas of the large intestine in mice. 2: Determine and compare the immune augmenting properties of PSK and VPS and correlate these parameters with tumor preventative and therapeutic activity. 3: Study the preventative and therapeutic activity of PSK and VPS activity in an Apc transgenic model of intestinal polyp and adenoma formation and its association with immune augmentation.
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