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

 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子在慢性胰腺炎中的作用及其与糖尿病和胰腺癌发展的关系。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纤维化的发展中起着关键作用。我们的临床前激素研究集中在神经介肽U（NMU），这是一种对胰岛素分泌具有抑制作用的神经肽。其对巨噬细胞和细胞因子的有效作用及其在伤害感受中的作用也是令人感兴趣的。这些观察结果可能会提供进一步了解慢性胰腺炎的自然史，以及了解胰腺癌背景下糖尿病发展的机制。为了应对这次RFA，我们组建了一支强大的科学团队，在临床胰腺炎、免疫学和发育生物学方面拥有广泛的互补专业知识。我们的建议在几个具体方面对RFA做出了高度回应。(1)作为一个临床中心，我们有经验和能力制定和执行标准化的多中心方案，用于招募慢性胰腺炎、糖尿病和胰腺癌患者队列。在本提案中，我们具体描述了一个慢性胰腺炎患者前瞻性纵向队列的方案，该队列伴有血液、尿液、粪便和胰泌素刺激的胰腺液的注释生物库。我们还有2个血液储存库;一个用于胰腺炎患者，另一个用于胰腺癌患者，可与联盟共享以支持回顾性研究。(2)我们将开发和验证细胞因子谱，可能有助于慢性胰腺炎的诊断和预测相关并发症的可能性。这些也可能导致目标，以支持临床试验，以阻止纤维化。(3)创新和 验证基于血清的NMU测定，可帮助诊断3c型糖尿病和胰腺癌诱导的糖尿病。这可能会导致新的诊断测试，以检测胰腺癌的早期阶段。与其他中心合作进一步研究和验证这些新观察结果的机会仍然是一个令人兴奋的机会，可以加速研究，改变慢性胰腺炎的管理及其相关的胰源性糖尿病并发症和胰腺癌的发展。

 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.