A Clinical Center to Study Immunological and Hormonal Biomarkers for the Diagnosis, Prediction and Treatment of Chronic Pancreatitis and its associated development to Diabetes and Pancreas Cancer

研究用于诊断、预测和治疗慢性胰腺炎及其与糖尿病和胰腺癌相关发展的免疫和激素生物标志物的临床中心

• 批准号: 9150617
• 负责人: Aida Habtezion
• 金额: $ 41.22万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9150617
• 关键词: Acute; Address; Beta Cell; Biological Assay; Biological Markers; Biology; Blood; Cachexia; Cells; Clinical; Clinical Trials; Collaborations; Detection; Development; Developmental Biology; Diabetes Mellitus; Diagnosis; Diagnostic tests; Disease; Early Diagnosis; Endocrine system; Enrollment; Enteroendocrine Cell; Enzyme-Linked Immunosorbent Assay; Exocrine pancreatic insufficiency; Feces; Fibrosis; Gastroenterology; Goals; Health; Hormonal; Hormones; Human; Immune; Immune response; Immune system; Immunology; Inflammatory; Insulin; Lead; Liquid substance; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Methods; Molecular; Natural History; Neuromedin U; Neuropeptides; Nociception; Output; Pancreas; Pancreatic Diseases; Pancreatic Ductal Adenocarcinoma; Pancreatitis; Pathogenesis; Patients; Prevention; Production; Protocols documentation; Recruitment Activity; Recurrence; Relapse; Research; Resources; Retrospective Studies; Rodent; Role; Sampling; Secretin; Serum; Signal Transduction; Staging; Urine; acute pancreatitis; base; biobank; candidate marker; chronic pain; chronic pancreatitis; cohort; cytokine; disability; experience; glucagon-like peptide 1; high risk; in vivo; insight; insulin secretion; interest; islet; macrophage; member; novel; novel diagnostics; outcome forecast; pre-clinical; prevent; prospective; repository; response; stellate cell

 DESCRIPTION (provided by applicant): This application to join the Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreas Cancer (CSCPDPC), seeks to examine the role of the immune system and of hormonal factors in chronic pancreatitis and its relationship to the development of diabetes and pancreas cancer. Our pre-clinical immunological studies suggest a pivotal role for macrophages, cytokines and stellate cells in predicting the development of fibrosis. Our pre-clinical hormonal studies focus on neuromedin U (NMU), which is a neuropeptide with an inhibitory effect on insulin secretion. It is also of interest for its potentil effect on macrophages and cytokines and its role in nociception. These observations may provide further insight into the natural history of chronic pancreatitis, and mechanisms for understanding the development of diabetes in the context of pancreas cancer. In response to this RFA, we have formed a strong scientific team with broad complementary expertise in clinical pancreatitis, immunology, and developmental biology. Our proposal is highly responsive to the RFA in several specific ways. (1) As a Clinical Center, we have the experience and capacity to develop and execute standardized multi-center protocols for enrolling cohorts of patients with chronic pancreatitis, diabetes and pancreas cancer. In this proposal, we specifically delineate a protocol for a prospective longitudinal cohort of patients with chronic pancreatitis accompanied with an annotated bio-repository of blood, urine, stool, and secretin stimulated pancreas fluid. We also have available 2 repositories of blood; one for patients with pancreatitis and the other of pancreas cancer, that are available for sharing with the consortium to support retrospective studies. (2) We will develop and validate cytokine profiles that may facilitate diagnosis of chronic pancreatitis and predict likelihood of associated complications. These may also lead to targets to support clinical trials to halt fibrosis. (3) We will develop and validate a serum-based assay of NMU that may help diagnose type 3c diabetes mellitus and pancreatic cancer-induced diabetes. This may lead to novel diagnostic tests to detect pancreatic cancer at earlier stages. The opportunity to further investigate and validate these novel observations in collaboration with other centers remains an exciting opportunity to accelerate research that could change chronic pancreatitis management and its associated complications of pancreatogenic diabetes and pancreas cancer development.

 描述（由申请人提供）：本申请加入慢性胰腺炎、糖尿病和胰腺癌研究联盟 (CSCPDPC)，旨在研究免疫系统和激素因素在慢性胰腺炎中的作用及其与发展的关系我们的临床前免疫学研究表明巨噬细胞、细胞因子和星状细胞在预测糖尿病和胰腺癌的发展中发挥着关键作用。我们的临床前激素研究重点是神经调节素 U (NMU)，它是一种对胰岛素分泌具有抑制作用的神经肽，它对巨噬细胞和细胞因子的潜在作用及其在伤害感受中的作用也令人感兴趣。进一步深入了解慢性胰腺炎的自然史，以及了解胰腺癌背景下糖尿病的发展机制。针对此 RFA，我们组建了一支拥有广泛互补专业知识的强大科学团队。我们的提案在几个具体方面对 RFA 做出了高度响应 (1) 作为临床中心，我们拥有开发和执行标准化多中心方案的经验和能力。慢性胰腺炎、糖尿病和胰腺癌患者在这项提案中，我们专门为慢性胰腺炎患者的前瞻性纵向队列制定了一项方案，并附有带注释的血液、尿液、粪便和促胰液素生物储存库。我们还有 2 个可用的血液储存库；一个用于胰腺炎患者，另一个用于胰腺癌，可与联盟共享以支持回顾性研究 (2) 我们将开发和验证可能的细胞因子谱。促进慢性胰腺炎和诊断预测相关并发症的可能性，这些也可能导致支持临床试验的目标，以阻止纤维化。 验证基于血清的 NMU 检测可能有助于诊断 3c 型糖尿病和胰腺癌诱发的糖尿病，这可能会导致新的诊断测试在早期阶段检测胰腺癌，从而有机会进一步合作研究和验证这些新的观察结果。与其他中心的合作仍然是一个令人兴奋的机会，可以加速研究，从而改变慢性胰腺炎的治疗及其胰源性糖尿病和胰腺癌发展的相关并发症。