ARACHIDONATE METABOLISM--A BIOMARKER IN PROSTATE CANCER

花生四烯酸代谢——前列腺癌的生物标志物

• 批准号: 2545393
• 负责人: FRED H FAAS
• 金额: $ 8.2万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2545393
• 关键词: African American; acyltransferase; arachidonate; bioassay; biomarker; biopsy; blood lipid; caucasian American; dehydroepiandrosterone; diet; enzyme activity; fatty acid metabolism; human subject; neoplasm /cancer invasiveness; nutrition related tag; phospholipase A2; prognosis; prostaglandin E; prostaglandins; prostate neoplasms; prostate specific antigen; prostate surgery; racial /ethnic difference; radioimmunoassay; testosterone; testosterone 5 alpha reductase

Prostate cancer is a leading cause of death in men. In autopsy studies it is equally prevalent in all populations. Yet, clinical prostate cancer is less common than expected from the high autopsy incidence and more common in African-Americans as compared to White Americans. The key question is what factors contribute to activation of indolent to invasive cancer and might these behave differently in various populations. The long-term objective of the present study is to identify a biochemical marker that will be a predictor for prostate malignancy and ultimately a predictor to distinguish patients with indolent from those with invasive prostate cancer. We think the decrease in arachidonic acid (AA) levels in prostate cancer is due to increased AA turnover resulting in increased prostaglandin (PG) production. PGE/2 may be important in the early development and/or growth of prostate cancer. Lysophospholipid acyltransferase (LPAT) and phospholipase A/2 activities form an acylation- deacylation cycle important in phospholipid fatty acid remodeling, providing AA to tissues and releasing AA for PG production. Our hypothesis is that our recently demonstrated marked increase in LPAT activity, a biomarker of the increased AA metabolism in prostate cancer, will be a predictor of the presence of and invasiveness of prostate cancer. Our specific aim is to measure prostatic LPAT activity, AA levels, and 5alpha-reductase activity in a cohort of patients with benign prostatic hyperplasia, and suspected or documented prostate cancer. These measurements will be correlated with the presence or absence of malignancy and with the invasiveness of the disease. The biochemical analyses will be performed in prostatic tissue obtained from patients undergoing needle biopsy of the prostate, radical prostatectomy and transurethral resection of the prostate. Correlations will also be made between the prostatic LPAT activity, AA levels, and 5alpha-reductase activity; and racial status, serum and RBC fatty acid composition, serum PSA, testosterone, and DHEA-S, dietary factors and other demographic data.

前列腺癌是男性死亡的主要原因。 在尸检研究中 在所有人群中同样普遍。 然而，临床前列腺癌是 高尸检发病率和更常见的不太普遍 与美国人相比，非裔美国人。 关键问题是 哪些因素导致激活侵入性癌症和 在各种人群中，这些行为可能会有所不同。 长期 本研究的目的是确定一个生化标志物 将成为前列腺恶性肿瘤的预测因子，并最终成为预测因子 区分懒惰的患者与侵入性前列腺的患者 癌症。 我们认为前列腺中花生四烯酸（AA）水平的降低 癌症是由于AA更新增加而导致增加 前列腺素（PG）生产。 PGE/2在早期可能很重要 前列腺癌的发展和/或生长。 溶血磷脂 酰基转移酶（LPAT）和磷脂酶A/2活性形成酰化 - 脱酰化周期在磷脂脂肪酸重塑中很重要， 向组织提供AA，并释放AA以生产PG。 我们的 假设是我们最近证明的LPAT明显增加 活性是前列腺癌中AA代谢增加的生物标志物， 将是前列腺存在和侵入性的预测指标 癌症。 我们的具体目的是测量前列腺LPAT活动，AA 一组良性患者中的水平和5阿尔法还原酶活性 前列腺增生，可疑或有记录的前列腺癌。 这些 测量将与存在或不存在恶性肿瘤有关 并具有疾病的侵入性。 生化分析将 可以在从接受针的患者获得的前列腺组织中进行 前列腺活检，根治性前列腺切除术和尿道切除术 前列腺。 前列腺之间也将建立相关性 LPAT活性，AA水平和5Alpha-还原酶活性；和种族 状态，血清和RBC脂肪酸组成，血清PSA，睾丸激素和 DHEA-S，饮食因素和其他人口统计数据。