The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials.
The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials.
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最有希望的替代终点生物标志物，用于在短期 II 期临床试验中筛选前列腺腺癌候选化学预防化合物。
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
R. Veltri
中科院分区：
文献类型：
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作者：
D. Bostwick;Burke Hb;T. Wheeler;Chung Lw;R. Bookstein;Pretlow Tg;Nagle Rb;R. Montironi;M. Lieber;R. Veltri
临床化学预防试验需要替代终点生物标志物（seb），以避免使用癌症发病率降低作为终点的研究周期过长和成本过高，特别是对于相对缓慢生长的肿瘤，如前列腺腺癌。SEBs与肿瘤的发展有直接关系，在易感个体的异常细胞中发生的频率较高。如果在短期研究中可以通过特定的干预方案来改变SEBs，那么进行长期研究的理由可能会得到加强。共识小组确定了一组在组织或血清中测量的小而易于管理的生物标志物，作为最有希望的前列腺癌化学预防，包括：(1)前列腺特异性抗原（PSA）；(2)形态学标记，如核的大小和圆度；(3)增殖标志物，如mb -1和PCNA；(4)核DNA含量（倍性）；(5)癌基因c-erbB-2 （HER-2/neu）表达；(6)血管生成;(7)高级别前列腺上皮内瘤变（PIN）。关于这些和其他生物标志物的信息是有限的，需要进一步调查。此外，选择这些因素主要是因为它们已被证明或建议用作预后因素，作为seb可能用处不大。人们一致认为，同时研究多个标记物而不是单个标记物，可以比较它们的相对效用，包括评估量化的便利性、敏感性、特异性以及阳性和阴性预测值。
Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.