Structural requirements for immunostimulation by plant lipids

植物脂质免疫刺激的结构要求

• 批准号: 8126345
• 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/8126345
• 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（由申请人提供）：化学疗法和放疗对癌症患者的免疫系统造成严重损害。尽管化学疗法诱导的中性粒细胞减少症可以通过重组粒细胞菌落刺激因子来缓解，但治疗由标准癌症治疗引起的损害的治疗选择有限，这强调了新药开发新药以改善癌症患者的生活质量（QOL）的重要性。我们最近的研究表明，在一种称为Juzen-Taiho-to（JTT）的东方草药配方中，一系列二酰基糖基糖苷（DGGS）是有效的免疫刺激剂，该配方临床用于重建日本癌症患者的免疫系统。拟议的研究有两个目标。即（i）JTT中DGG系列的结构阐明以及这些化合物的结构活性关系的表征。一旦澄清了DGG对免疫刺激的结构要求，就可以根据简单的DGG框架，通过合理设计的新免疫刺激剂充分探索其治疗潜力。因此，拟议的研究开辟了令人兴奋的可能性，即可以通过化学定义的，口服的小分子来改善癌症患者的质量。 公共卫生相关性：该研究项目将表征草药免疫促进剂的化学成分，该促进剂长期以来一直临床用于日本的癌症患者。预计这项研究将为重建癌症患者的免疫系统开放一种令人兴奋的可能性，从而改善了他们的生活质量，口服的小分子具有长期证明的安全性和有效性。