AMYLIN AND ITS RELEASING FACTOR IN THE EARLY DIAGNOSIS OF PANCREATIC CANCER

胰淀素及其释放因子在胰腺癌早期诊断中的作用

• 批准号: 6269799
• 负责人: THOMAS E ADRIAN
• 金额: $ 19.8万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-15 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6269799
• 关键词: bile obstruction; blood chemistry; blood glucose; cancer complication; clinical research; diabetes mellitus; early diagnosis; human population study; human subject; insulin; laboratory rabbit; method development; neoplasm /cancer diagnosis; pancreas hormone; pancreas neoplasms; pancreatitis; peptide hormone biosynthesis; protein purification; protein sequence; radioimmunoassay

Pancreatic cancer is associated with profound insulin resistance, resulting in diabetes in up to 80% of patients. This metabolic abnormality is tumor dependent and disappears after tumor resection, despite the loss of islets. Amylin is a pancreatic hormone that inhibits muscle glycogen synthesis and reduces food intake. In most pancreatic cancer patients, amylin levels are elevated in the fasting state. Even though diabetes may not be a major problem for the management of patients with pancreatic cancer, measurement of amylin may be a valuable marker for the early diagnosis of the disease, at least in a proportion of patients. Furthermore, the increased amylin levels appear to result from stimulation of peri-tumoral islets by a tumor-derived peptide (amylin releasing peptide of ARP). It is likely that, compared with amylin, circulating ARP levels are elevated in an even higher proportion of pancreatic cancer patients. The major goals of this proposal are as follows: 1. To investigate the specificity of elevated circulating amylin in pancreatic cancer, by investigating patients with pancreatitis, biliary obstruction, newly diagnosed diabetes, pancreatic cancer or other malignancies. 2. To purify and sequence ARP and develop a radioimmunoassay to measure this peptide. 3. To establish whether ARP is a better marker for pancreatic cancer than amylin, by measurement in the above groups of patients. 4. To determine the value of amylin and ARP as early indicators of pancreatic cancer, by measuring the peptides in families with a high risk of developing the disease, and by measuring them in samples from pancreatic cancer patient collected several years prior to their cancer diagnosis. This study may aid in the development of an early screening technique for detecting pancreatic cancer at an early, curable stage. In addition, it will improve our understanding of the role played by the islets in this disease.

胰腺癌与严重的胰岛素抵抗有关， 导致高达80%的患者患有糖尿病。这种新陈代谢 异常是肿瘤依赖的，在肿瘤切除后消失， 尽管失去了小岛。胰淀素是一种胰腺激素，能抑制 肌肉糖原合成，减少食物摄入量。在大多数胰腺 癌症患者禁食状态下胰淀素水平升高。连 尽管糖尿病可能不是管理的主要问题 胰腺癌患者，胰淀素的测定可能是一种 对疾病的早期诊断有价值的标志，至少在 患者比例。此外，胰淀素水平的增加也出现了 肿瘤来源的胰岛对肿瘤周围胰岛的刺激 肽(ARP的胰淀素释放肽)。很可能，与之相比 有了胰淀素，循环中的ARP水平甚至更高 胰腺癌患者的比例。这次会议的主要目标是 建议书如下： 1.探讨慢性胰腺炎患者循环胰淀素升高的特异性 胰腺癌，通过调查胰腺炎、胆道炎患者 梗阻、新诊断的糖尿病、胰腺癌或其他 恶性肿瘤。 2.纯化和测序ARP并建立放射免疫分析方法 量一量这种多肽。 3.确定ARP是否是胰腺癌更好的标记物 比胰淀素，通过测量在上述患者组。 4.确定胰淀素和ARP作为早期指标的价值 胰腺癌，通过测量高血糖家系中的多肽 患上这种疾病的风险，并通过测量来自 胰腺癌患者在癌症前几年收集的资料 诊断。 这项研究可能有助于早期筛查技术的发展 用于在早期、可治愈阶段检测胰腺癌。此外, 这将使我们更好地了解小岛在 这种病。