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: 6217490
• 负责人: THOMAS E ADRIAN
• 金额: $ 20.16万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-25 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6217490
• 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。 这种代谢 异常是肿瘤依赖性的并且在肿瘤切除后消失， 尽管失去了小岛 胰淀素是一种胰腺激素， 肌肉糖原合成和减少食物摄入。 在大多数胰腺 在癌症患者中，胰淀素水平在禁食状态下升高。 甚至 虽然糖尿病可能不是管理的主要问题， 胰腺癌患者，胰淀素的测量可能是一个 这是一个有价值的标志物，用于疾病的早期诊断，至少在 患者比例。 此外，增加的胰淀素水平似乎 由肿瘤衍生的细胞刺激肿瘤周围的胰岛引起， 胰淀素释放肽（amylin releasing peptide of阿普）。 很可能，相比之下， 与胰淀素，循环阿普水平升高，甚至更高， 胰腺癌患者的比例。 本项目的主要目标是 建议如下： 1.为了研究循环胰淀素升高的特异性， 胰腺癌，通过调查胰腺炎患者，胆 梗阻，新诊断的糖尿病，胰腺癌或其他 恶性肿瘤 2.目的：纯化阿普并测定其序列，建立ARP的放射免疫分析方法， 测量这个肽。 3.确定阿普是否是胰腺癌的更好标记物 胰淀素，通过测量在上述患者组中。 4.为了确定胰淀素和阿普作为早期指标的价值， 胰腺癌，通过测量高血糖家族中的肽， 风险发展的疾病，并通过测量他们的样本， 胰腺癌患者在癌症发生前几年收集的数据 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，本发明还提供了一种方法， 它将增进我们对这些岛屿所起作用的理解， 这种疾病。