Noninvasive Detection of Prostate Cancer with a Label-Free Imaging System

使用无标记成像系统无创检测前列腺癌

• 批准号: 9388033
• 负责人: Jing Yong Ye
• 金额: $ 19.84万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9388033
• 关键词: Address; Alpha Cell; Benign Prostatic Hypertrophy; Biological Assay; Biological Markers; Biosensor; Cancer Patient; Cancerous; Cell Line; Cells; Characteristics; Chronic; Clinic; Core Biopsy; Crystallization; Cytology; Detection; Development; Diagnosis; Diagnostic; Digital Rectal Examination; Disease; Elements; Epithelial Cells; Harvest; Image; Imagery; Immunofluorescence Immunologic; Individual; Infection; Inflammation; Label; Lead; Legal patent; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Massage; Methods; Microscopy; Monitor; Nanostructures; Normal Cell; Optics; Patients; Persons; Property; Prostate; Prostate carcinoma; Prostate-Specific Antigen; Prostatic; Refractive Indices; Sampling; Screening for Prostate Cancer; Sensitivity and Specificity; Specificity; Specimen; Spectrum Analysis; Structure; Surface; System; Technology; Testing; Therapeutic; Time; Urine; base; cancer cell; cancer diagnosis; cell type; cellular imaging; clinical practice; design and construction; imaging platform; imaging system; improved; interest; men; molecular marker; novel; novel strategies; photonics; prostate biopsy; prostate cancer cell; prostate cancer cell line; response; sensor; stem; treatment effect

Project Summary: The prostate-specific antigen (PSA) has been widely used as a biomarker in current clinical practice to screen men for prostate cancer, although issues associated with this method including high false-positive rate are well known. This is because in addition to prostate cancer, infection and chronic inflammation or benign prostatic hyperplasia (BPH) may also cause elevations in PSA levels. Therefore, there is tremendous interest in developing other approaches with higher specificity for improved detection of prostate cancer in recent years. Despite the significant progress in developing a number of new molecular biomarkers, none of them has been successful enough to replace PSA test so far. On the other hand, using exfoliated prostate cancer cells isolated from urine specimens for diagnosing the carcinoma of the prostate has long been proposed. Although the examination at cellular levels provides excellent specificities in contrast to PSA tests, past attempts at diagnosing prostate cancer via traditional urine cytology were abandoned due to unacceptably low sensitivities. The challenge in increasing sensitivity mainly stems from lacking sensitive and specific markers that allow visualization and differentiation of malignant prostate cancer cells through immunofluorescence labeling. Instead of using immunofluorescence labeling, a new approach has been proposed in this project to use cell refractive indices (RI) as a native contrast parameter for label-free, noninvasive detection of prostate cancer, because RI properties directly reflect certain macromolecular constituents and their nanostructures of a cell, which are different between cancer and normal cells. A novel imaging system based on a patented photonic crystal biosensor will be designed and constructed for label-free detection of malignant prostate cancer cells from urine with unparalleled sensitivity and specificity. Successful development of the proposed technology will allow reducing unnecessary multicore prostate biopsy due to false- positive PSA results and address the unmet urgent demand of a noninvasive, accurate approach for prostate cancer screening. Furthermore, the proposed technology is highly transformative, which may potentially lead to other widespread applications, such as detection of other cancer or diseases and monitoring therapeutic treatment effects.

项目总结： 前列腺特异性抗原(PSA)在目前的临床实践中被广泛用作生物标志物 筛查男性前列腺癌，尽管与这种方法相关的问题包括高假阳性 利率是众所周知的。这是因为除了前列腺癌，感染和慢性炎症或 良性前列腺增生症(BPH)也可能导致PSA水平升高。因此，有 非常有兴趣开发其他具有更高特异性的方法来改进检测 前列腺癌是近年来发生的一种癌症。尽管在开发一些新的分子方面取得了重大进展 生物标记物，到目前为止还没有一个足够成功的方法来取代PSA检测。另一方面 用从尿液标本中分离的前列腺癌细胞诊断前列腺癌 长期以来，人们一直在提议进行前列腺手术。尽管细胞水平的检查提供了极好的 与PSA检测相比，过去通过传统尿液诊断前列腺癌的尝试具有特异性 由于灵敏度低得令人无法接受，细胞学被放弃了。提高敏感度的挑战 主要原因是缺乏敏感和特异的标记物来可视化和区分 恶性前列腺癌细胞的免疫荧光标记。 代替使用免疫荧光标记，该项目提出了一种新的方法来 使用细胞折射率(RI)作为自然对比度参数，进行无标记、无创检测 前列腺癌，因为RI特性直接反映了某些大分子成分和它们的 细胞的纳米结构，这在癌症细胞和正常细胞之间是不同的。一种新型成像系统 基于专利的光子晶体生物传感器将被设计和制造用于无标记检测 从尿液中分离出恶性前列腺癌细胞具有无与伦比的敏感性和特异性。成功 拟议技术的开发将允许减少不必要的多核前列腺活检 假阳性PSA结果并解决未得到满足的非侵入性、准确的方法的迫切需求 用于前列腺癌筛查。此外，拟议的技术具有高度的变革性，这可能 可能导致其他广泛应用，例如检测其他癌症或疾病以及 监测治疗效果。