Chemical cytometry for neoplasia prognosis-Barrett's esophagus

描述（由申请人提供）：本申请是对RFA-CA-06-003《新兴技术在癌症研究中的应用》的回应。该RFA：“邀请申请研究项目，以评估新兴分子技术的有用性，这些技术已准备好初步应用于癌症研究中的临床或生物学问题。项目的设计应证明该技术是稳健的，并产生可重复的测量结果。项目的设计还应收集初步数据，以支持在未来以临床或生物学为重点的项目中使用技术。“该应用程序结合了华盛顿大学化学和病理学系以及弗雷德哈钦森癌症研究中心的研究人员的努力。这些研究人员将进行一项试点研究，以评估癌症研究的新技术，化学细胞术。该技术监测单细胞中的蛋白质和生物胺表达，并将用于研究从西雅图巴雷特食管队列患者活检中分离的细胞。我们将系统地确定巴雷特食管活检组织中细胞组成的变化。我们将从活检组织中分离的单个隐窝中解剖20个细胞，并对这些细胞进行化学细胞计数。这项研究将提供理解蛋白质表达的变化沿着一个隐窝和在发展过程中的干细胞成其分化形式。我们将对从单次活检获得的三个隐窝中分离的细胞进行化学细胞术。这些隐窝将密切相关，研究将提供有关克隆内变异的信息。我们将对从同一患者的三次活检获得的隐窝中分离的细胞进行化学细胞术。本研究将提供有关克隆间变异的信息。我们将生成5名患者的指纹，这将提供患者间差异的信息。作为这些研究的结果，我们将确定需要进行分析以表征瘤形成的细胞或隐窝的数量。基于这些结果，我们将提出一项后续资助，用于系统验证化学细胞术对腺癌进展的预后，以及开发适合大规模临床分析的平台。

DESCRIPTION (provided by applicant): This application is in response to RFA-CA-06-003, Applications of emerging technologies for Cancer Research. This RFA:" invites applications for research projects to evaluate the usefulness of emerging molecular technologies that are ready for initial application to clinical or biological questions in cancer research. Projects should be designed to demonstrate that the technology is robust and yields reproducible measurements. Projects should also be designed to gather preliminary data to support the use of the technology in a future project(s) with a clinical or biological focus." The application combines the efforts of researchers in the Departments of Chemistry and Pathology at the University of Washington and at the Fred Hutchinson Cancer Research Center. These researchers will perform a pilot study to evaluate new technology for cancer research, chemical cytometry. This technology monitors protein and biogenic amine expression in single cells, and will be evaluated for the study of cells isolated from biopsies obtained from patients in the Seattle Barrett's Esophagus Cohort. We will systematically determine the variance in cellular composition within Barrett's esophagus biopsies We will dissect 20 cells from a single crypt isolated from a biopsy and perform chemical cytometry on those cells. This study will provide understanding of the variance in protein expression along a crypt and during development of a stem cell into its differentiated form. We will perform chemical cytometry on cells isolated from three crypts obtained from a single biopsy. These crypts will be closely related and the study will provide information on the intraclonal variation. We will perform chemical cytometry on cells isolated from crypts obtained from three biopsies from the same patient. This study will provide information on the interclonal variation. We will generate fingerprints from 5 patients, which will provide information on the between-patient variance. As a result of these studies, we will have identified the number of cells or crypts necessary to be assayed to characterize the neoplasia. Based on these results, we will propose a follow-up grant for the systematic validation of chemical cytometry for prognosis of the progression to adenocarcinoma, and for the development of a platform appropriate for large-scale clinical analysis.