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Methylated Galectin-3 DNA as a Marker for Early Diagnosis of Prostate Cancer

甲基化 Galectin-3 DNA 作为前列腺癌早期诊断的标志物

基本信息

批准号：
7896745
负责人：
HAFIZ AHMED
金额：
$ 7.5万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7896745
关键词：
Accounting Alleles American Joint Committee on Cancer Benign Prostatic Hypertrophy Biological Biological Assay Biological Markers Biopsy Cancer Etiology Cessation of life CpG Islands Cytosine DNA Detection Development Diagnosis Diagnostic Diagnostic Neoplasm Staging Digital Rectal Examination Disease Early Diagnosis Figs - dietary Galectin 3 Gene Expression Genes Glutathione S-Transferase Goals Hypermethylation Inflammation Lead Liquid substance Malignant Neoplasms Malignant neoplasm of prostate Methods Methylation Monitoring for Recurrence Newly Diagnosed Oncogenes Patients Pattern Principal Investigator Prostate Prostate-Specific Antigen Prostatic Neoplasms Protein Family RARB gene Research Project Grants Sampling Screening for Prostate Cancer Screening for cancer Screening procedure Sensitivity and Specificity Serum Serum Markers Site Specificity Specimen Staging Telomerase Test Result Testing Therapeutic Tissues Tumor Suppressor Genes Tumor Tissue Tumor stage United States Urine Ursidae Family base bisulfite cancer diagnosis cohort design effective therapy galactose-binding protein improved member men programs promoter successful intervention tool tool development tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer is the second most common cancer in men, and the second leading cause of cancer death. However, patients with prostate cancer can be effectively treated and cured, when diagnosed in early stages (i.e. the stages when cancer is still confined to the prostate gland). Combined with the digital rectal examination, the prostate specific antigen (PSA) test has been widely used to detect prostate cancer in its early stages. An elevated PSA level may be an indication of prostate cancer. However, various conditions such as enlargement or inflammation of prostate can cause elevated levels of PSA. Conversely, PSA levels may be normal despite the presence of prostate cancer. Thus, the PSA screening method for early detection of prostate cancer is not suitable due to highly prevalent false positive and negative PSA test results. Therefore, a reliable marker for early detection of prostate cancer is urgently needed. Transcriptional silencing of tumor suppressor gene expression due to hypermethylation of the gene promoters is believed to contribute to the neoplastic progression. Thus, methylated DNAs can serve as biomarkers for early detection of cancer. But, the methylation of most genes correlates positively with tumor grade and stage and thus the detection of these methylated DNAs is not necessarily suitable to identify prostate cancer at early stages, especially at stages I and II (the critical stages for effective treatment and cure). A prostate cancer gene (PCG) has recently been found to be heavily methylated in stages I and II tumor compared to the normal and later stages of tumor tissues. The methylation in the PCG allows development of PCR-based sensitive and specific tools that clearly identify the early stages of prostate cancer in tissues as well as in biological fluids such as serum and urine. The goal of the proposed studies is to establish 'proof of concept' using a large number of tissue and urine specimens. Results from these studies will lead to the development of a non-invasive diagnostic tool not only for early detection, but also for therapeutic guidance and recurrence monitoring of prostate cancer in urine.

描述（由申请人提供）：前列腺癌是男性中第二常见的癌症，也是癌症死亡的第二大原因。然而，前列腺癌患者在早期诊断时（即癌症仍局限于前列腺的阶段）可以得到有效治疗和治愈。结合直肠指检，前列腺特异性抗原（PSA）检测已被广泛用于早期检测前列腺癌。PSA水平升高可能是前列腺癌的指征。然而，各种情况，如前列腺肿大或炎症，可导致PSA水平升高。相反，PSA水平可能是正常的，尽管存在前列腺癌。因此，用于前列腺癌早期检测的PSA筛查方法由于非常普遍的假阳性和阴性PSA测试结果而不适合。因此，迫切需要一种可靠的早期检测前列腺癌的标志物。由于基因启动子的超甲基化导致的肿瘤抑制基因表达的转录沉默被认为有助于肿瘤的进展。因此，甲基化DNA可以作为癌症早期检测的生物标志物。但是，大多数基因的甲基化与肿瘤分级和阶段正相关，因此这些甲基化DNA的检测不一定适合于在早期阶段，特别是在I和II期（有效治疗和治愈的关键阶段）鉴定前列腺癌。最近发现前列腺癌基因（PCG）在I期和II期肿瘤中与正常和晚期肿瘤组织相比被高度甲基化。PCG中的甲基化允许开发基于PCR的敏感和特异性工具，这些工具可以清楚地识别组织以及生物液体（如血清和尿液）中前列腺癌的早期阶段。拟议研究的目标是使用大量组织和尿液标本建立“概念验证”。这些研究的结果将导致开发一种非侵入性诊断工具，不仅用于早期检测，而且用于治疗指导和尿液中前列腺癌的复发监测。