Zinc-Based Early Detection of Prostate Cancer

基于锌的前列腺癌早期检测

• 批准号: 7487719
• 负责人: CHRISTOPHER J. FREDERICKSON
• 金额: $ 84.35万
• 依托单位: NEUROBIOTEX, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487719
• 关键词: Acinus organ component; Adenocarcinoma; Antibodies; Area; Area Analyses; Area Under Curve; Atrophic; Biopsy; Cancer Detection; Carrier Proteins; Cells; Clinical; Companions; Condition; Consensus; Core Biopsy; Data; Detection; Diagnosis; Disease; Drops; Fluorescence; Freezing; Gland; Glass; Growth; Histology; Histopathology; Hospitals; Image; Inflammatory; Invasive; Label; Life; Liquid substance; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Massage; Measurement; Measures; Medical History; Microscopy; Molecular; Numbers; Operative Surgical Procedures; Outcome; Pathologist; Pathology; Patients; Phase; Phase II Clinical Trials; Pilot Projects; Procedures; Prostate; Prostate Adenocarcinoma; Prostatectomy; Prostatic; Prostatic Diseases; Prostatic Intraepithelial Neoplasias; Proteins; Public Health; Publishing; Puncture biopsy; Quartz; Reporting; Roentgen Rays; Sample Size; Sampling; Schedule; Score; Screening for Prostate Cancer; Sensitivity and Specificity; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Sorting - Cell Movement; Staging; Staining method; Stains; Statistically Significant; Study Subject; Subcategory; Testing; Tissues; Urethra; Work; Zinc; base; cohort; design; digital imaging; falls; insight; instrument; man; men; meter; rectal; virtual; zinc-binding protein

DESCRIPTION (provided by applicant): In Phase I we showed that our measurement of free zinc in expressed prostatic fluid is a promising clinical indicator of prostate cancer. Indeed, in our two pilot studies and one prior published study, prostatic fluid zinc scores gave areas under the receiver operating curve (AUROC) of .79, .92, and .99 for detecting biopsy-confirmed prostatic adenocarcinoma. Our test is non-invasive, requiring only a few drops of prostatic fluid obtained from the urethral meatus during a rectal prostate examination with brief prostate massage. The zinc measurement is fast, cheap, easy, and exquisitely accurate. Our Phase II study has two components. In Study IIA we will increase our sample size to better estimate the sensitivity and specificity of our test. We will collect samples of prostatic fluid from a carefully selected sample of approximately 100 men expected to have prostate adenocarcinoma and approximately 100 men expected to be cancer free. Upon histopathological confirmation of adenocarcinoma or the absence of adenocarcinoma in all men, a receiver operating curve analysis will be conducted to determine the sensitivity, specificity and overall area under the curve (AUROC) for the detection of adenocarcinoma by the measurement of zinc in prostatic fluid. This study will show how useful the zinc test is for detecting prostate cancer. The subjects in this study will be (i) men scheduled for prostatectomy (ii) men scheduled for cysto-prostatectomy (iii) men scheduled for saturation (64 core) needle biopsy and (iv) men scheduled for conventional biopsy. In Study IIB we will establish which prostatic disease conditions are accompanied by the loss of zinc sequestering and secretion. Thus, we will take tissue sections from the prostate glands of the subjects in Study IIA, stain them with H&E and (in some cases) antibodies to disease- defining proteins. Regions with specific prostatic pathology such as PIA (proliferative inflammatory atrophy), PIN (prostatic intraepithelial neoplasia) or adenocarcinoma will be marked on digital images of the sections, then adjacent sections will be imaged in X-RAY fluorescence and zinc histofluorescence microscopy to show the distribution of elemental and free zinc , respectively. Comparison of the classical histology with the zinc maps by digitally superimposing them will show how zinc sequestration (and therefore secretion) changes in each of the different types and stages of pathology. Data in the literature indicate that zinc sequestration and secretion are suppressed in PIN and suppressed in healthy-appearing acini that are near an adenocarcinoma, suggesting a field effect. If confirmed by our work, this would explain how even relatively small adenocarcinomas markedly suppress zinc secretion of the gland. Every year in the US about 1,500,000 prostate biopsies are done, revealing only about 300,000 cancers. Still, about 30,000 men die from cancers too advanced for effective treatment. We believe our zinc test could allow earlier and more certain detection of potentially aggressive cancers, thus saving lives. PUBLIC HEALTH NARAVTIVE: This Phase II SBIR is designed to determine the sensitivity and specificity of a zinc test for prostate cancer. The test measures zinc in massage-expressed prostatic fluid, and it only takes about 60 sec to get the fluid and about 60 sec to make the measurement on a table-top, $5000 instrument. The test is intended to supplement other tests, including the PSA and DRE. Because the zinc falls in cancer but does not fall in BPH, the zinc tests has the potential to distinguish these two conditions.

描述（由申请人提供）：在第一阶段，我们表明我们对表达的前列腺液中游离锌的测量是前列腺癌的一个有前途的临床指标。事实上，在我们的两项试点研究和一项先前发表的研究中，前列腺液锌评分给出的受试者工作曲线下面积 (AUROC) 分别为 0.79、0.92 和 0.99，用于检测活检证实的前列腺腺癌。我们的测试是非侵入性的，只需在直肠前列腺检查过程中从尿道口获取几滴前列腺液并进行短暂的前列腺按摩。锌的测量快速、便宜、简单且极其准确。我们的第二阶段研究有两个组成部分。在研究 IIA 中，我们将增加样本量，以更好地估计我们测试的敏感性和特异性。我们将从精心挑选的大约 100 名预计患有前列腺癌的男性和大约 100 名预计无癌症的男性样本中收集前列腺液样本。在组织病理学证实所有男性均患有腺癌或不存在腺癌后，将进行受试者工作曲线分析，以确定通过测量前列腺液中的锌检测腺癌的敏感性、特异性和曲线下总面积 (AUROC)。这项研究将展示锌测试对于检测前列腺癌有多么有用。本研究的受试者为 (i) 计划进行前列腺切除术的男性 (ii) 计划进行膀胱前列腺切除术的男性 (iii) 计划进行饱和（64 芯）针刺活检的男性和 (iv) 计划进行传统活检的男性。在研究 IIB 中，我们将确定哪些前列腺疾病伴有锌螯合和分泌的丧失。因此，我们将从研究 IIA 中受试者的前列腺中取出组织切片，用 H&E 和（在某些情况下）疾病定义蛋白的抗体对它们进行染色。具有特定前列腺病理学的区域，例如PIA（增殖性炎症萎缩）、PIN（前列腺上皮内瘤变）或腺癌，将在切片的数字图像上标记，然后将相邻切片在X射线荧光和锌组织荧光显微镜下成像，以分别显示元素和游离锌的分布。通过数字叠加将经典组织学与锌图进行比较，将显示锌隔离（以及分泌）在每种不同类型和病理阶段的变化。文献中的数据表明，锌的螯合和分泌在 PIN 中受到抑制，在腺癌附近的外观健康的腺泡中也受到抑制，这表明存在场效应。如果我们的工作得到证实，这将解释即使是相对较小的腺癌也能显着抑制腺体的锌分泌。美国每年进行约 1,500,000 例前列腺活检，仅发现约 300,000 种癌症。尽管如此，仍有约 30,000 名男性死于晚期癌症，无法进行有效治疗。我们相信我们的锌检测可以更早、更确定地检测出潜在的侵袭性癌症，从而挽救生命。公共卫生叙述：该 II 期 SBIR 旨在确定前列腺癌锌检测的敏感性和特异性。该测试测量按摩前列腺液中的锌，仅需约 60 秒即可获得液体，并在价值 5000 美元的台式仪器上进行测量约 60 秒。该测试旨在补充其他测试，包括 PSA 和 DRE。由于锌在癌症中下降，但在良性前列腺增生中却不会下降，因此锌测试有可能区分这两种疾病。