Prevention of Cancer by Coriolus versicolor Mushroom

描述（由申请人提供）：蛋白结合多糖K （PSK）是一种从芫花菇（CV）的子实体和菌丝体中提取的热液提取物，在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，并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的癌症患者用作营养补充剂。鉴于这些补充剂的广泛使用，对临床（PSK）和营养补充剂（VPS）制剂的生物活性进行比较研究是必要的，我们建议比较它们的肿瘤预防和治疗活性，并扩展我们对其基于免疫增强的作用机制的理解。该建议将解决口服PSK和VPS对小鼠结直肠癌的免疫调节活性和预防和治疗活性的假设。这一假设将通过1,2-二甲基肼（DMH）诱导的结肠直肠肿瘤和Apcmin转基因胃肠道息肉和腺瘤模型两种原位肿瘤模型进行验证。我们的长期目标是启动结肠直肠癌的临床研究，如果这些研究得到保证，使用VPS和本提案确定的免疫替代物来支持I期剂量寻找方案。我们提出了三个特定的目的来验证我们的假设：1 .确定并比较PSK和VPS对DMH诱导的小鼠大肠肿瘤前病变、腺瘤和腺癌的预防和治疗活性。2：确定并比较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联系起来。3：研究PSK和VPS活性在Apc转基因肠息肉和腺瘤形成模型中的防治作用及其与免疫增强的关系。

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.