A Biomarker Study of COX-2 Inhibitors in IPMN

描述（由申请人提供）：寻找胰腺癌成功化疗的努力令人失望。一些患者患胰腺癌的风险增加，或者可能有癌前胰腺病变，这使他们更容易发生胰腺癌。在这些个体中，化学预防措施可能会阻止胰腺癌的未来发展。胰腺导管内乳头状粘液性肿瘤（IPMN）是胰腺癌的前兆。这些癌前病变在胰腺导管系统内形成并分泌粘液物质。IPMN的恶性潜能被认为是其发育不良程度的函数。我们的初步数据表明，考克斯-2的表达和活性（PGE 2水平）可能确实与异型增生的程度。环氧合酶-2似乎在胰腺肿瘤发生中起重要作用。考克斯-2抑制剂在IPMN中的作用尚未确定。我们正在进行塞来昔布（考克斯-2抑制剂）在IPMN患者中的生物标志物研究。由于IPMN是导管内病变，我们建议检查IPMN活检和塞来昔布治疗前后的胰腺导管液，以确定考克斯-2抑制剂对考克斯-2活性（PGE 2水平）、考克斯-2表达、异型增生分期以及增殖、凋亡和血管生成指数的影响。我们还将通过细胞阻滞/免疫细胞化学ELISA和SELDI研究塞来昔布对IPMN恶性进展新标志物表达的影响。重要的是，这些研究可能提供临床证据，支持考克斯-2抑制剂用于IPMN和其他胰腺癌前病变患者中胰腺癌发生高风险的化学预防的多机构研究。

DESCRIPTION (provided by applicant): Efforts at finding a successful chemotherapy for pancreatic cancer have been disappointing. Some patients are at increased risk of pancreatic cancer or may have pre-malignant pancreatic lesions which predispose them to later pancreatic cancer development. In these individuals, chemopreventative measures may block future development of pancreatic cancer. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are precursors of pancreatic cancer. These precancerous lesions form inside the pancreatic ductal system and secrete a mucinous material. The malignant potential of IPMNs is thought to be a function of their degree of dysplasia. Our preliminary data suggests COX-2 expression and activity (PGE2 level) may indeed be associated with degree of dysplasia. Cyclooxygenase-2 appears to play a significant role in pancreatic tumorigenesis. The role of COX-2 inhibitors in IPMN has not been determined. We are conducting a biomarker study of celecoxib (COX-2 inhibitor) in patients with IPMN. Since IPMNs are intraductal lesions, we propose to examine IPMN biopsies and pancreatic ductal fluid pre- and post-celecoxib treatment to determine the effect of COX-2 inhibitors on COX-2 activity (PGE2 levels), COX-2 expression, dysplastic stage, and indices of proliferation, apoptosis and angiogenesis. We will also investigate celecoxib's effects on the expression of novel markers of IPMN malignant progression by cell block/immunocytochemistry ELISA and SELDI. Importantly, these studies may provide clinical evidence in support of a multi-institutional study of COX-2 inhibitors for chemoprevention in patients with IPMN and other precancerous pancreatic lesions at high risk for the development of pancreatic cancer.