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(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，血管加压素(VP)相关多肽和VP受体将为更好地检测、诊断和最终治疗乳腺癌和DCIS提供敏感和可靠的靶点。我们最近的数据显示，VP基因的表达是所有或大多数乳腺癌和DCIS的共同特征。这种表达不仅产生了表面标志物GRSA，还产生了VP、VP相关糖肽(VAG)和ProVP作为潜在的疾病血液标志物。加压素受体的表达似乎也是因为VP是乳腺癌的一种自分泌生长因子。 目标针对：(I)建立有效的血浆和组织ELISA法，用于检测导管和小叶浸润性乳腺癌；(Ii)评估这种ELISA法对检测残余侵袭性疾病和可能预测生存的价值；(Iii)确定是否可以像在组织中一样，利用同样的ELISA法检测血浆中的DCIS；(Iv)确定一种似乎是乳腺癌特有的异常VP受体(AbnV2R)在乳腺癌和DCIS中的分布和丰度，以确定它是否可用作乳腺癌检测和治疗的新标记物。 这些研究将使用RIA以及ELISA法、RT-PCR法、克隆和DNA测序、免疫组织化学、抗体生成、密度定量Western分析和流式细胞术。 我们研究的一个成功的终点将是产生广泛可用的和敏感的方法来检测和定位所有或大多数个人的疾病。另一个成功的终点将是发现这些相同的方法可以成功地监测当前的治疗方法，并可能导致新的和更有效的治疗方法。