Zinc-Based Early Detection of Prostate Cancer

基于锌的前列腺癌早期检测

• 批准号: 7913731
• 负责人: CHRISTOPHER J. FREDERICKSON
• 金额: $ 6.25万
• 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 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7913731
• 关键词: Acinus organ component; Adenocarcinoma; Antibodies; Area; Area Under Curve; Atrophic; Biopsy; Cancer Detection; Carrier Proteins; Cells; Clinical; Companions; Consensus; Core Biopsy; Data; Detection; Diagnosis; Disease; Drops; Fluorescence; Freezing; Gland; Glass; Growth; Histology; Histopathology; Hospitals; Image; Inflammatory; Label; Life; Liquid substance; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Massage; Measurement; Measures; Medical History; Microscopy; Molecular; Needle biopsy procedure; 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; Quartz; Reporting; Roentgen Rays; Sample Size; Sampling; Schedule; Screening for Prostate Cancer; Sensitivity and Specificity; Small Business Innovation Research Grant; Sorting - Cell Movement; Staging; Staining method; Stains; Study Subject; Subcategory; Testing; Tissues; Urethra; Work; Zinc; base; cohort; design; digital imaging; effective therapy; 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，我们表明我们在表达的前列腺液中对游离锌的测量是前列腺癌的有希望的临床指标。实际上，在我们的两项初步研究和一项先前发表的研究中，前列腺流体锌评分在接收器工作曲线（AUROC）下为.79，.92和.99，用于检测活检证实的前列腺腺癌。我们的测试是无创的，在直肠前列腺检查期间，只需要从尿道肉类获得几滴前列腺液，并短暂前列腺按摩。锌的测量快速，便宜，容易且精确。我们的II期研究有两个组成部分。在研究IIA中，我们将增加样本量，以更好地估计测试的敏感性和特异性。我们将从预期的大约100名患有前列腺腺癌和约100名预期无癌症的男性的男性的样本中收集前列腺液样品。在所有男性中对腺癌的组织病理学确认或缺乏腺癌的缺乏后，将进行接收器的工作曲线分析，以确定曲线下的灵敏度，特异性和整体面积（AUROC）以检测腺癌的检测。这项研究将表明锌检测对于检测前列腺癌的有用程度。这项研究的受试者将是（i）计划进行前列腺切除术（II）的男性，该男性安排了安排饱和（64 Core）针头活检的男性（III）男性和计划进行常规活检的男性。在研究IIB中，我们将确定哪些前列腺疾病状况伴随着锌隔离和分泌的丧失。因此，我们将从研究IIA中的受试者的前列腺中采取组织切片，用H＆E染色它们，以及（在某些情况下）抗病蛋白质的抗体。具有特定前列腺病理学的区域，例如PIA（增殖性炎症性萎缩），PIN（前列腺上皮内肿瘤）或腺癌的区域将在切片的数字图像上标记，然后在相邻切片中进行X射线荧光和Zinc Histofluororecophy的邻近切片，并释放元素的分布。通过数字叠加将经典组织学与锌图的比较将表明锌隔离（因此分泌）如何在病理的每种不同类型和阶段发生变化。文献中的数据表明，锌固醇和分泌在销钉中被抑制，并在靠近腺癌的健康表现acini中抑制，这表明田间作用。如果通过我们的工作确认，这将解释甚至相对较小的腺癌如何显着抑制腺体的锌分泌。每年在美国，大约有1,500,000个前列腺活检，只有大约30万次癌症。尽管如此，大约有30,000名男性死于癌症，无法进行有效治疗。我们认为，我们的锌测试可以允许更早，更确定对潜在侵略性癌症的检测，从而挽救生命。公共卫生Naravtive：此II期SBIR旨在确定锌对前列腺癌的敏感性和特异性。该测试测量按摩表达的前列腺液中的锌，仅需60秒即可获得流体和60秒的时间，就可以在桌面上进行5000美元的仪器进行测量。该测试旨在补充其他测试，包括PSA和DRE。由于锌属于癌症，但不属于BPH，因此锌试验有可能区分这两种情况。