Pathogenic Factors And Determinants Of Prognosis In Pati

帕蒂的致病因素和预后决定因素

• 批准号: 6546655
• 负责人: ROBERT JENSEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6546655
• 关键词: Zollinger Ellison syndrome; clinical research; endocrine disorder; endocrine neoplasm; epidermal growth factor; gastrins; gastrointestinal neoplasms; gene expression; growth factor receptors; hepatocyte growth factor; human subject; intestine neoplasm; loss of heterozygosity; molecular oncology; molecular pathology; multiple endocrine neoplasia; neoplasm /cancer genetics; neoplastic growth; neoplastic process; oncogenes; orphan disease /drug; pancreatic islet neoplasm; pathologic process; prognosis; statistics /biometry; tumor suppressor genes

Recent studies demonstrate gastrinomas, similar to carcinoid tumors and all other pancreatic endocrine tumors (PET's) except insulinomas, frequently (60-90%) are malignant and some may have an aggressive course. The molecular pathogenesis, not only for the tumors themselves, but also for determining their growth behavior is almost completely unknown. Recent studies demonstrate that in contrast to many other more common cancers neither oncogenes nor common tumor suppressor genes (p53, retinoblastoma, VHL gene, etc.) are generally altered in gastrinomas, carcinoids or other PET's. Recent analyses at NIH have identified a cohort of 25% of patients in whom gastrinomas pursued an aggressive clinical course. Both clinical and laboratory characteristics that distinguish patients with an aggressive course are being sought by statistical analysis as well as correlations with possible molecular changes in the gastrinoma that may correlate with prognosis and tumor growth. Our recent studies demonstrate that the tumor suppressor gene, p16, which is involved in maintaining cell cycle control, is frequently (50%) altered in gastrinomas, entirely due to methylation of CG-rich islands in the promoter region. Furthermore, alterations are found in the MEN1 gene in 40%. At present we are investigating the importance of overexpression of growth factors (EGFR, HGFR, and VEFR)in gastrinomas, alterations in the HER-2/neu oncogene and LOH in chromosome one in PET's because alterations in each of these correlate with aggressive growth in a number of nonendocrine tumors. The identification of molecular alteration that correlate with tumor growth will allow identification of patients with tumors that warrant more aggressive treatment.

最近的研究表明，胃泌素瘤，类似于类癌肿瘤和所有其他胰腺内分泌肿瘤（PET），除了胰岛素瘤，经常（60-90%）是恶性的，有些可能有一个侵略性的过程。不仅是肿瘤本身的分子发病机制，而且决定其生长行为的分子发病机制几乎完全未知。最近的研究表明，与许多其他更常见的癌症相比，癌基因和常见的肿瘤抑制基因（p53，视网膜母细胞瘤，VHL基因等）都没有表达。在胃泌素瘤、类癌或其他PET中通常发生改变。NIH最近的分析确定了一组25%的患者，其中胃泌素瘤进行了积极的临床过程。通过统计分析以及与胃泌素瘤中可能与预后和肿瘤生长相关的分子变化的相关性，正在寻找区分具有侵袭性过程的患者的临床和实验室特征。我们最近的研究表明，参与维持细胞周期控制的肿瘤抑制基因p16在胃泌素瘤中经常（50%）改变，完全是由于启动子区域富含CG的岛屿甲基化。此外，在40%的MEN 1基因中发现了改变。目前，我们正在研究胃泌素瘤中生长因子（EGFR、HGFR和VEFR）过表达、HER-2/neu癌基因改变和PET中1号染色体洛的重要性，因为这些改变都与许多非内分泌肿瘤的侵袭性生长相关。与肿瘤生长相关的分子改变的鉴定将允许鉴定患有需要更积极治疗的肿瘤的患者。