Full Project 3

完整项目 3

• 批准号: 10762318
• 负责人: BO HAN
• 金额: $ 12.52万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762318
• 关键词: 3-Dimensional; ATAC-seq; Acinar Cell; Acinus organ component; Address; African American; African American population; Black Populations; Black race; California; Cancer cell line; Caring; Cell Line; Cell Reprogramming; Cells; Chronic; Coculture Techniques; Collagen; Conditioned Culture Media; Data; Development; Disease; Disparity; Duct (organ) structure; Ductal Epithelial Cell; Early Diagnosis; Early treatment; Education; Event; Experimental Models; Extracellular Matrix; Fibronectins; Florida; Funding; Gender; Gene Expression; Genes; Goals; Heterogeneity; Hispanic; Hispanic Populations; Histone Deacetylase Inhibitor; Human; Immune; Immunofluorescence Immunologic; In Situ; Incidence; Individual; Inflammation; Inflammatory; Institution; Latino; Latino Population; Lesion; Link; Macrophage; Malignant Neoplasms; Malignant neoplasm of pancreas; Metabolic stress; Metaplasia; Methods; Microscopic; Molecular; Normal Range; Outcome; Oxidative Stress; Pancreas; Pancreatic Ductal Adenocarcinoma; Pathway interactions; Patients; Penetration; Peptide Hydrolases; Pharmaceutical Preparations; Phenotype; Pilot Projects; Process; Prognosis; Publishing; Race; Role; Sampling; Stains; Stromal Cells; System; Tissues; Trichostatin A; anticancer research; biophysical properties; biophysical techniques; cancer health disparity; chronic pancreatitis; combat; comorbidity; effective therapy; health equity; improved; inhibitor; irritation; mortality; mouse model; novel; pancreas development; pancreatic ductal adenocarcinoma model; pancreatic metaplasia; pancreatic stellate cell; pharmacologic; prevent; racial disparity; stellate cell; therapeutic target; transcriptome sequencing; treatment response; tumor microenvironment

ABSTRACT – FULL PROJECT 3 ADM Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating cancers with poor prognosis and rising incidence. To combat this deadly disease, we should direct our efforts towards preventing PDAC or halting the progression of precursor lesions to invasive disease parallel to developing novel treatments. One of the earliest known initiating events for PDAC is the process of acinar-to-ductal metaplasia (ADM). Understanding and reduction of ADM formation may reduce early PDAC development and progression. Blacks display a significantly increased incidence and mortality from PDAC compared to other races for unknown reasons. The role of race on pancreatic ADM and its contributions to the development and progression of PDAC need to be addressed. In our previously funded CaRE2 Pilot Project, we used normal pancreatic acinar tissues from Black, White and Hispanic donors to study the impact of race on acinar-to-ductal metaplasia (ADM) and found that Blacks undergo ADM to a greater extent than Whites or Hispanics. In this proposed Full Project as part of the CaRE2 renewal, we will expand on and extend our previous pilot project by including diseased tissues from CP and PDAC from White, Black, and Hispanic donors since accumulating evidence suggest that chronic pancreatitis (CP) is a major precursor to the development of PDAC. We will investigate the impact of race on the cellular and molecular events regulating the interplay between ADM and the microenvironment. Guided by our published and unpublished results, we hypothesize that the racial disparities seen in PDAC are related to differences in how the pancreas microenvironment develops during ADM, which means that ADM and its surrounding microenvironment can be used as a target to treat PDAC. We propose the following specific aims to address this hypothesis: Aim 1: The influence of race on ADM of healthy pancreas, CP, and PDAC-associated acinar tissues. Aim 2: The roles of pancreatic stellate cells and macrophages in ADM and ADM reversal Aim 3: Contributions of the race to ADM reversal and cell heterogeneity. The proposed studies will impact the field of pancreatic cancer by providing a missing link between disparities, ADM, tumor microenvironment, and potential treatments for CP and PDAC. The specific focus on the racial contributions of microenvironment remolding during pancreatic metaplasia aligns with the Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center’s overall goal to eliminate cancer health disparities among Black and Latino individuals in California, Florida, and across the U.S.

摘要-全项目3 adm