VP peptides and receptors in diagnosis of breast cancer.

VP 肽和受体在乳腺癌诊断中的应用。

• 批准号: 6966384
• 负责人: WILLIAM G NORTH
• 金额: $ 13.75万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6966384
• 关键词: autoradiography; bioimaging /biomedical imaging; biomarker; breast neoplasms; clinical research; diagnosis design /evaluation; enzyme linked immunosorbent assay; flow cytometry; glycopeptides; hormone inhibitor; hormone receptor; human subject; immunocytochemistry; laboratory mouse; neoplasm /cancer diagnosis; nucleic acid sequence; patient oriented research; polymerase chain reaction; radioimmunoassay; radiotracer; receptor expression; vasopressins; western blottings

DESCRIPTION (provided by applicant):The objective of this project is to improve diagnostic techniques for breast cancer and breast ductal carcinoma in situ (DCIS). The hypothesis being tested is that vasopressin (VP)-related peptides, and VP receptors will provide sensitive and reliable targets for better detection, diagnosis, and eventual treatment of breast cancer and DCIS. Our recent data show VP gene expression is a feature common to all or most breast cancers and DCIS. This expression gives rise not only to a surface marker, GRSA, but also to VP, VP-related glycopeptide (VAG) and ProVP as potential blood markers of disease. Vasopressin receptors also seem to be expressed because VP is an autocrine growth factor for breast cancer. Goals are directed towards: (i) developing effective plasma and tissue ELISA assays for detecting ductal and lobular invasive breast cancer; (ii) assessing the value of such ELISA assays for detecting residual invasive disease and possibly forecasting survival; (iii) ascertaining if the same ELISA assays can be utilized for detecting DCIS in plasma as they most probably can in tissues; and (iv) determining the distribution and abundance in breast cancer and DCIS of an abnormal VP receptor (abnV2R) that is seemingly unique to breast cancer to ascertain if it can be used as a new marker for detection and treatment of breast cancer. These investigations will employ, RIA as well as ELISA assay, RT-PCR, cloning, and DNA sequencing, immunohistochemistry, antibody generation, Western analysis with densitometric quantitation, and flow cytometry. One successful end-point of our studies would be the generation of widely available and sensitive methods for detecting and localizing disease in all, or most, individuals. Another successful end-point would be the finding that these same methods can successfully monitor current treatments, and potentially lead to new and more effective ones.

描述（由申请人提供）：该项目的目标是改进乳腺癌和乳腺导管原位癌（DCIS）的诊断技术。正在测试的假设是加压素 (VP) 相关肽和 VP 受体将为更好地检测、诊断和最终治疗乳腺癌和导管原位癌提供敏感且可靠的靶标。我们最近的数据显示 VP 基因表达是所有或大多数乳腺癌和 DCIS 的共同特征。这种表达不仅产生表面标记物 GRSA，而且还产生 VP、VP 相关糖肽 (VAG) 和 ProVP 作为疾病的潜在血液标记物。加压素受体似乎也有表达，因为 VP 是乳腺癌的自分泌生长因子。 目标是： (i) 开发有效的血浆和组织 ELISA 检测方法来检测导管和小叶浸润性乳腺癌； (ii) 评估此类 ELISA 检测对于检测残留侵袭性疾病并可能预测生存的价值； (iii) 确定是否可以使用相同的 ELISA 检测方法来检测血浆中的 DCIS，就像在组织中检测 DCIS 一样； (iv) 确定乳腺癌和导管原位癌中异常 VP 受体 (abnV2R) 的分布和丰度，该受体似乎是乳腺癌所特有的，以确定它是否可以用作乳腺癌检测和治疗的新标志物。 这些研究将采用 RIA 以及 ELISA 测定、RT-PCR、克隆和 DNA 测序、免疫组织化学、抗体生成、光密度定量蛋白质印迹分析和流式细胞术。 我们研究的一个成功终点是产生一种广泛可用且敏感的方法来检测和定位所有或大多数个体的疾病。另一个成功的终点是发现这些相同的方法可以成功地监测当前的治疗方法，并可能导致新的、更有效的治疗方法。