Systems Biochemistry in Lung Cancer: Toward a Mechanistic Understanding of NSCLC

肺癌的系统生物化学：了解非小细胞肺癌的机制

基本信息

批准号：
9025455
负责人：
Teresa Whei-Mei Fan
金额：
$ 133.71万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-19 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9025455
关键词：
Address Analytical Biochemistry Animal Model Animals Arginine Benign Biochemical Biochemical Pathway Biochemistry Bioinformatics Cancer Biology Cancer Gene Mutation Cell Culture Techniques Cell model Cells Cessation of life Clinical Trials Collaborations Congresses Data Death Rate Detection Development Disease Early Diagnosis Epithelial Cells Fibroblasts Food Interactions Future Generations Genes Glucans Glucose Glutamine Goals Human Hypoxia Immune Immune system Immunomodulators Implant In Situ Individual Informatics Investigation Knowledge Label Laboratories Link Lung Lung Neoplasms Macrophage Activation Malignant Neoplasms Malignant neoplasm of lung Mass Spectrum Analysis Mediating Metabolic Metabolic Pathway Metabolism Modeling Molecular Mus Mutation Analysis Natural Products Nature Non-Small-Cell Lung Carcinoma North America Nutrient Pathway Analysis Patients Pattern Physicians Plasma Process Property Proteomics Refractory Resected Resolution Risk Role Sampling Scientist Slice Staging Structure of parenchyma of lung Survival Rate System Technology Testing Time Tissues Tumor-Derived Xenograft procedure arginase base cancer cell cancer subtypes cell transformation cohort exosome host neoplasm interaction human subject human tissue immune activation immunoregulation improved insight interest macrophage meetings metabolic phenotype metabolomics mouse model neoplastic cell novel strategies oncology outcome forecast pre-clinical programs research study response stable isotope subcutaneous tool transcriptomics treatment strategy tumor tumor immunology tumor metabolism tumor microenvironment tumor progression

项目摘要

DESCRIPTION (provided by applicant): Deaths from lung cancer are the highest of all cancers in North America and elsewhere and, because of the long incubation time, are likely to remain so for the foreseeable future. Furthermore, although the 5-year survival rate of stage I lung cancer is 60-70%, later stage disease has a very poor prognosis. Accurate detection of asymptomatic early stage lung cancer in individuals at risk is currently unreliable. A better understanding of the basic biochemistry of lung cancers is a prerequisite to mechanism-based reliable early detection of the disease, and to improved approaches to treatment. The very complexity of the transformed cells, and the variable host-tumor interactions, makes the problem refractory to any single approach. A systems biochemistry approach in which lung cancers are studied at the mechanistic level in the laboratory, in mouse models and in human subjects offers the opportunity to address the complexity of cancer development and progression. The use of stable isotope resolved metabolomics provides the necessary direct biochemical information about lung cancer with minimal processing that is not otherwise available. This program will address the problem in a 3-pronged approach, based on the following integrated projects: Project 1: Cellular Systems Biochemistry. Microenvironmental nutrient availability and immune modulation in lung cancer cells. Project 2; Preclinical Systems Biochemistry. Using SIRM in Human NSCLC xenograft mouse to determine biochemical mechanisms of immunomodulator ¿-glucan. Project 3: Translational Systems Biochemistry. Molecular mechanisms of NSCLC and response to ¿-glucan by SIRM. The three projects will use a common mechanistic approach to understanding cancer biochemistry namely stable isotope resolved metabolomics (SIRM) that we have been developing over the last eight years. The analytical requirements will be met in the SIRM Analytical Core, which also supplies the necessary sample handling and bioinformatics support for the three projects. Core A provides overall administrative support.

描述（由申请人提供）：在北美和其他地方，肺癌的死亡率是所有癌症中最高的，并且由于潜伏期长，在可预见的未来很可能仍然如此。然而，尽管 5 年生存率I 期肺癌的发病率为 60-70%，晚期疾病的预后非常差，目前对高危个体中无症状早期肺癌的准确检测尚不可靠。肺癌的生物化学是基于机制的可靠的疾病早期检测和改进治疗方法的先决条件，转化细胞的复杂性以及可变的宿主-肿瘤相互作用使得任何单一方法都难以解决该问题。在实验室、小鼠模型和人类受试者中对肺癌进行机制水平研究的系统生物化学方法为解决癌症发生和进展的复杂性提供了机会。稳定同位素解析代谢组学的使用提供了机会。通过最少的处理获得有关肺癌的必要直接生化信息，该计划将基于以下综合项目，通过三管齐下的方法解决该问题：项目 1：细胞系统营养可用性和免疫调节。项目 2；在人类 NSCLC 异种移植小鼠中使用 SIRM 来确定免疫调节剂的生化机制 ¿ -葡聚糖。项目 3：非小细胞肺癌的分子机制和反应 ¿ SIRM 的葡聚糖。这三个项目将使用一种常见的机制方法来理解癌症生物化学，即我们在过去八年中开发的稳定同位素解析代谢组学 (SIRM)，SIRM 分析核心将满足分析要求。还为这三个项目提供必要的样品处理和生物信息学支持，核心 A 提供全面的行政支持。