Structural requirements for immunostimulation by plant lipids

植物脂质免疫刺激的结构要求

• 批准号: 8289478
• 负责人: AKIRA KAWAMURA
• 金额: $ 11.29万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-13 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8289478
• 关键词: Academy; Acquired Immunodeficiency Syndrome; Animal Model; Applications Grants; Asians; Biological Assay; Biological Factors; Cancer Patient; Cells; Chemicals; Chemistry; Core Facility; Data; Development; Diamond; Drug Formulations; Elements; Evaluation; Fatty Acids; Glycosides; Goals; Grant; Group Meetings; Head; Herbal Medicine; Immune; Immune system; Immunization; Immunologic Adjuvants; Immunology; Investigation; Japan; Journals; Label; Length; Libraries; Lipids; Manuscripts; Medical; Metabolic; Minority; Molecular; Molecular Probes; National Center for Complementary and Alternative Medicine; National Institute of Allergy and Infectious Disease; National Institute of General Medical Sciences; Natural Products Chemistry; Neutropenia; New York; Outcome; Paper; Pattern; Pharmaceutical Chemistry; Pharmaceutical Preparations; Plants; Publications; Quality of life; Radiation therapy; Radioisotopes; Recombinant Granulocyte Colony Stimulating Factor; Research; Research Personnel; Research Project Grants; Safety; Sampling; Science; Screening procedure; Secure; Series; Staging; Structure; Structure-Activity Relationship; Therapeutic; Toxic effect; Universities; Writing; acyl group; analog; base; cancer immunotherapy; cancer therapy; chemotherapy; college; design; drug development; improved; in vivo; innovation; lipoteichoic acid; meetings; novel; pharmacophore; programs; public health relevance; small molecule; stereochemistry; symposium; therapeutic evaluation

DESCRIPTION (provided by applicant): Chemotherapy and radiotherapy cause severe damages to the immune system of cancer patients. Although chemotherapy-induced neutropenia can be alleviated with recombinant granulocyte colony-stimulating factor, therapeutic options to treat damages caused by standard cancer therapy are limited, which underscores the importance of the development of new drugs to improve the quality of life (QOL) of cancer patients. Our recent study indicates that a series of diacylglyceryl glycosides (DGGs) are potent immunostimulants in an oriental herbal formulation called Juzen-taiho-to (JTT), which is clinically used to rebuild the immune system of cancer patients in Japan. The proposed study has two aims; namely, (i) structural elucidation of the series of DGGs in JTT and characterization of the structure-activity relationship of these compounds. Once the structural requirements for the immunostimulation by DGGs are clarified, it would become possible to fully explore their therapeutic potential with rationally designed new immunostimulants based on the simple DGG framework. The proposed research, therefore, opens an exciting possibility that QOL of cancer patients can be improved with a cocktail of chemically defined, orally available small molecules. PUBLIC HEALTH RELEVANCE: This research project will characterize the chemical components of an herbal immune booster, which has long been used clinically for cancer patients in Japan. The study is expected to open an exciting possibility to rebuild the immune system of cancer patients, thereby improving their quality of life, with orally available small molecules with long proven safety and efficacy.

描述（申请人提供）：化疗和放疗对癌症患者的免疫系统造成严重损害。尽管重组粒细胞集落刺激因子可以缓解化疗引起的中性粒细胞减少症，但治疗标准癌症治疗造成的损害的治疗选择有限，这凸显了开发新药以改善癌症患者生活质量（QOL）的重要性。我们最近的研究表明，一系列二酰基甘油糖苷 (DGG) 是一种名为 Juzen-taiho-to (JTT) 的东方草药配方中的有效免疫刺激剂，该配方在日本临床上用于重建癌症患者的免疫系统。拟议的研究有两个目的；即，(i) JTT 中一系列 DGG 的结构解析以及这些化合物的构效关系的表征。一旦明确了 DGG 免疫刺激的结构要求，就有可能通过基于简单的 DGG 框架合理设计的新型免疫刺激剂来充分探索其治疗潜力。因此，拟议的研究开启了一个令人兴奋的可能性，即可以通过化学成分确定的口服小分子混合物来改善癌症患者的生活质量。 公共健康相关性：该研究项目将表征草药免疫增强剂的化学成分，这种草药长期以来一直在日本临床上用于治疗癌症患者。这项研究有望为重建癌症患者的免疫系统提供令人兴奋的可能性，从而改善他们的生活质量，口服小分子的安全性和有效性已得到长期证明。