Prevention of Cancer by Coriolus versicolor Mushroom

描述（由申请方提供）：蛋白结合多糖K（PSK）是一种从云芝（CV）蘑菇的子实体和菌丝体中提取的热水提取物，与口服氟尿嘧啶化疗联合治疗胃癌时具有显著的辅助活性，在日本被批准用于该适应症。最近，CV蘑菇的热水提取物已被美国癌症患者用作营养补充剂。鉴于这些补充剂的广泛使用，有必要对临床（PSK）和营养补充剂（VPS）制剂的生物活性进行比较研究，我们建议比较它们的肿瘤预防和治疗活性，并扩展我们对它们基于免疫增强的作用机制的理解。该提案将解决以下假设：口服PSK和VPS导致小鼠结肠直肠癌的免疫调节活性以及预防和治疗活性。该假设将使用两种自体肿瘤模型进行检验：1，2-二甲基肼（DMH）诱导的结直肠肿瘤和胃肠道息肉和腺瘤的Apcmin转基因模型。我们的长期目标是启动结直肠癌的临床研究，如果这些研究有必要，使用VPS和本提案确定的免疫替代物来支持I期剂量探索方案。本研究拟从三个方面来验证我们的假设：1.比较PSK和VPS对DMH诱发的小鼠大肠癌前病变、腺瘤和腺癌的预防和治疗作用。第二章：确定和比较PSK和VPS的免疫增强特性，并将这些参数与肿瘤预防和治疗活性相关联。第三章：研究PSK和VPS活性在肠息肉和腺瘤形成的Apc转基因模型中的预防和治疗活性及其与免疫增强的相关性。

DESCRIPTION (provided by applicant): 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.