(10.) The Gut Microbiome and Responses to Neoadjuvant Chemoradiation in Rectal Cancer Patients

(10.) 直肠癌患者的肠道微生物群和对新辅助放化疗的反应

基本信息

批准号：
9250105
负责人：
GRACE Y. CHEN
金额：
$ 20.23万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9250105
关键词：
Achievement Address Affect Bacteria Cancer Etiology Cancer Patient Chemicals Chemosensitization Colon Carcinoma Colorectal Cancer Combination Drug Therapy Data Development Disease Epithelial Evaluation Excision Feces Fluorouracil Foundations Future Goals Health Histologic Immune response In complete remission Inflammation Inflammatory Response Injury Intestinal Mucosa Intestines Lead Malignant Neoplasms Mass Spectrum Analysis Morbidity - disease rate Mucous Membrane Mus Neoadjuvant Therapy Operative Surgical Procedures Pathogenesis Pathologic Pathway interactions Patient-Focused Outcomes Patients Pelvis Population Predisposition Radiation Rectal Cancer Rectum Recurrence Resected Ribosomal RNA Role Sampling Specimen T-Lymphocyte Subsets Therapeutic Effect Tumor Immunity United States Woman Work cancer recurrence cancer risk cancer therapy cancer type chemoradiation chemotherapy gut microbiome gut microbiota high risk improved intestinal homeostasis men metabolomics metaproteomics microbiome microbiota mortality prospective public health relevance repaired response standard care treatment response tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer is the third most common type of cancer in the United States and the second leading cause of cancer-related mortality among men and women combined. Rectal cancers are located in the rectum deep in the pelvis, and it is estimated that there will be approximately 40,000 new cases of rectal cancer in 2015. The treatment of locally advanced rectal cancers is different from colon cancer in that the standard approach is neoadjuvant chemotherapy, specifically with 5-FU, combined with radiation prior to surgery. This approach was shown to reduce the rate of local recurrence that can cause substantial morbidity and mortality. The achievement of pathologic complete response after neoadjuvant chemo-radiation has also been associated with improved patient outcomes. Both chemotherapy and radiation can cause changes in the intestinal mucosa, in particular changes in intestinal epithelial barrier function and induction of inflammatory responses. In addition chemotherapy and radiation can also affect the composition of the gut microbiome, which, in turn, can affect immune responses that are important for chemotherapy efficacy. Thus, we hypothesize that the composition of the gut microbiome and changes in the activities of the gut microbiome during neoadjuvant therapy are associated with tumor responses. In the proposed work, we will obtain stool samples from locally advanced rectal cancer patients before, during, and after completion of neoadjuvant chemo-radiation and determine the composition and functional activities of the microbiome through 16S bacterial sequencing and mass spectrometry, respectively. The overall goal will be to determine if there are specific bacterial populations or functions that are important for achieving complete pathologic response as assessed by histologic evaluation of tumor specimens surgically removed after completion of neoadjuvant therapy. These studies will lay the foundation for future work to improve tumor responses to chemo-radiation and patient outcomes by manipulation of the gut microbiome.

描述（由适用提供）：大肠癌是美国第三大常见的癌症类型，也是男性和女性中与癌症相关死亡率的第二大主要原因。直肠癌位于骨盆深处的直肠癌，据估计，2015年将有大约40,000例新的直肠癌新病例。局部晚期直肠癌的治疗与结肠癌不同，因为标准方法是NeoAdjuvant Chemothy疗法，特别是在5-FU中与5-FU，共同融合了curguty。这种方法被证明可降低可能导致大量发病率和死亡率的局部复发率。新辅助化学辐射后，病理完全反应的实现也与改善患者结局有关。化学疗法和放射线都会引起肠粘膜的变化，特别是肠上皮屏障功能的变化以及炎症反应的诱导。另外，化学疗法和放射线也会影响肠道微生物组的组成，这反过来又会影响对化学疗法效率很重要的免疫复杂。这就是我们假设肠道微生物组的组成以及新辅助治疗期间肠道微生物组活性的变化与肿瘤反应有关。在拟议的工作中，我们将在新辅助化学辐射之前，期间和之后从局部晚期直肠癌患者那里获得粪便样品，并分别通过16S细菌测序和质谱法确定微生物组的组成和功能活性。总体目标是确定是否存在特定的细菌群体或功能对于实现完全病理反应很重要的，如通过组织学评估新辅助治疗后通过手术切除的肿瘤物种评估。研究将为将来的工作奠定基础，以通过操纵肠道微生物组来改善肿瘤对化学辐射和患者结局的反应。