Analysis of estrogens in serum and plasma from postmenopausal women: past present, and future.
Analysis of estrogens in serum and plasma from postmenopausal women: past present, and future.
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DOI：
10.1016/j.steroids.2010.01.012
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发表时间：
2010-04
期刊：
影响因子：
2.7
通讯作者：
Blair, Ian A.
中科院分区：
文献类型：
--
作者：
Blair, Ian A.
关键词：
先前的研究表明，选择乳腺癌高风险女性接受化学预防药物治疗可以提高获益/风险比。然而，实施这一策略的进一步努力将需要开发新模型来预测特定个体的乳腺癌风险。血浆或血清雌激素升高的绝经后妇女患乳腺癌的风险增加。因此，对绝经后妇女雌激素生物合成中涉及的各种酶的作用进行了详细综述。此外，还检查了不同雌激素代谢物作为乳腺癌病因学危险因素的潜在遗传毒性和/或增殖作用。不幸的是，目前用于分析血浆和血清雌激素的许多生物分析方法已被证明是有问题的。如果有可靠的方法来量化绝经后妇女血浆或血清中的雌二醇及其主要代谢物，风险评估将可能取得重大进展。高效液相色谱 (HPLC) 与放射免疫分析 (RIA) 相结合，目前为分析绝经后妇女血清样本中的雌酮和雌二醇提供了最灵敏、最有效的免疫分析方法。然而，在解释乳腺癌流行病学研究时，许多其他免疫测定观察到的个体间特异性差异引起了重大问题。克服使用基于 RIA 的方法所涉及的固有测定问题几乎是不可能的，特别是对于多种雌激素。为了可靠地测量血浆或血清中的多种雌激素，有必要将稳定同位素稀释方法与液相色谱-串联质谱 (LC-MS/MS) 结合使用。当与现代三重四极杆质谱仪和纳流液相色谱结合使用时，预电离的雌激素衍生物可以获得极高的灵敏度。使用[13C6]-雌酮作为内标，已证明可以在柱上分析亚fg（低摩尔）量的雌酮作为其预电离的Girard T (GT)衍生物。这表明，未来将有可能对血清和血浆中的多种雌激素代谢物进行常规 LC-MS 检测，其浓度甚至低于目前的定量下限 0.4 pg/mL (1.6 pmol/L)。预电离衍生化策略易于实施，这使得在目前采用 LC-MS/MS 方法的实验室中轻松引入高灵敏度稳定同位素稀释方法成为可能。这将有助于保存重要的血浆和血清样本，因为可以使用低样本量进行高灵敏度分析。
Previous studies have shown that the selection of women who are at high breast cancer risk for treatment with chemoprevention agents leads to an enhanced benefit/risk ratio. However, further efforts to implement this strategy will require the development of new models to predict the breast cancer risk of particular individuals. Postmenopausal women with elevated plasma or serum estrogens are at increased risk for breast cancer. Therefore, the roles of various enzymes involved in the biosynthesis of estrogens in postmenopausal women have been reviewed in detail. In addition, the potential genotoxic and/or proliferative effects of the different estrogen metabolites as risk factors in the etiology of breast cancer have been examined. Unfortunately, much of the current bioanalytical methodology employed for the analysis of plasma and serum estrogens has proved to be problematic. Major advances in risk assessment would be possible if reliable methodology were available to quantify estradiol and its major metabolites in the plasma or serum of postmenopausal women. High performance liquid chromatography (HPLC) coupled with radioimmunoassay (RIA) currently provides the most sensitive and best validated immunoassay method for the analysis for estrone and estradiol in serum samples from postmenopausal women. However, inter-individual differences in specificity observed with many other immunoassays have caused significant problems when interpreting epidemiologic studies of breast cancer. It is almost impossible to overcome the inherent assay problems involved in using RIA-based methodology, particularly for multiple estrogens. For reliable measurements of multiple estrogens in plasma or serum, it will be necessary to employ stable isotope dilution methodology in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) Extremely high sensitivity can be obtained with pre-ionized estrogen derivatives when employed in combination with a modern triple quadrupole mass spectrometer and nanoflow LC. Using [13C6]-estrone as the internal standard it has proved possible to analyze estrone as its pre-ionized Girard T (GT) derivative in sub-fg (low amol) amounts on column. This suggests that in the future it will be possible to routinely conduct LC-MS assays of multiple estrogen metabolites in serum and plasma at even lower concentrations than the current lower limit of quantitation of 0.4 pg/mL (1.6 pmol/L). The ease with which the pre-ionization derivatization strategy can be implemented will make it possible to readily introduce high sensitivity stable isotope dilution methodology in laboratories that are currently employing LC-MS/MS methodology. This will help conserve important plasma and serum samples as it will be possible to conduct high sensitivity analyses using low sample volumes.
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影响因子：
13.3
作者：
Blamey, R;Collins, J;Volpe, A
通讯作者：
Volpe, A
影响因子：
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作者：
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作者：
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DOI：
10.1158/1055-9965.epi-08-0262
发表时间：
2008-08
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
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作者：
Eliassen AH;Missmer SA;Tworoger SS;Hankinson SE
通讯作者：
Hankinson SE
DOI：
10.1006/bbrc.2002.6658
发表时间：
2002-03-29
影响因子：
3.1
作者：
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通讯作者：
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