Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.

Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.
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DOI:
10.1002/ijc.23717
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发表时间:
2008-10-15
影响因子:
6.4
通讯作者:
Low, Philip S.
Low, Philip S.
中科院分区:
医学1区
文献类型:
--
作者:
He, Wei;Kularatne, Surnith A.;Kalli, Kimberly R.;Prendergast, Franklyn G.;Amato, Robert J.;Klee, George G.;Hartmann, Lynn C.;Low, Philip S.

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循环肿瘤细胞 (CTC) 的定量可以提供有关恶性肿瘤阶段、疾病进展发作和治疗反应的信息。为了更准确地定量 CTC,我们合成了 2 种高亲和力肿瘤特异性配体(叶酸-AlexaFluor 488 和 DUPA-FITC)的荧光缀合物,其结合肿瘤细胞的效率比荧光抗体高 20 倍以上。在这里,我们确定这些肿瘤特异性染料是否可用于定量癌症患者外周血样本中的 CTC。通过优化的密度梯度离心方案从卵巢癌和前列腺癌患者的外周血中分离出富含 CTC 的级分,并用上述荧光配体进行标记。然后通过流式细胞术对 CTC 进行定量。 20 名卵巢癌患者中,有 18 名检测到 CTC(平均 222 CTC/ml;中位数 15 CTC/ml;最多 3,118 CTC/ml),而 16 名性别匹配的正常志愿者中的 CTC 数量可以忽略不计(平均 0.4 CTC/ml;中位数 0.3 CTC/ml;最多 1.5 CTC/ml;p < 0.001, χ2)。 13 名前列腺癌患者中的 10 名也检测到了 CTC(平均 26 CTC/ml,中位数 14 CTC/ml,最多 94 CTC/ml),但在 18 名性别匹配的健康捐赠者中未检测到(平均 0.8 CTC/ml,中位数 1,最大 3 CTC/ml;p < 0.0026,χ2)。由于 CTC 标记效率较低,肿瘤特异性荧光抗体在定量 CTC 方面的效率要低得多。使用肿瘤特异性荧光配体标记外周血中的CTC,可以提供一种简单、准确且灵敏的方法来确定血液中循环的癌细胞数量。
Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ ml; p < 0.001, χ2). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, χ2). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.
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影响因子: 45.3
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发表时间: 2004-08-19
影响因子: 158.5
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发表时间: 1988-06-30
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影响因子: 64.8
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