在接受达卡巴嗪和干扰素治疗的患者中，血液血管生成 microRNA 水平与循环内皮细胞和血管生成蛋白的关系。
The association of blood angioregulatory microRNA levels with circulating endothelial cells and angiogenic proteins in patients receiving dacarbazine and interferon.
机构信息
Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
出版信息
J Transl Med. 2012 Dec 5;10:241. doi: 10.1186/1479-5876-10-241.
BACKGROUND
Blood biomarkers are needed to monitor anti-angiogenic treatments for cancer. The association of blood levels of microRNAs (miRs) implicated in angiogenesis with circulating endothelial cells (CEC) and with angiogenic proteins was examined in patients administered drugs with anti-angiogenic activity.
METHODS
Blood was collected from patients with uveal melanoma enrolled on an adjuvant therapy trial in which they were treated sequentially with dacarbazine and interferon-alfa-2b. Plasma levels of nine angioregulatory miRs, miR-16, 20a, 106a, 125b, 126, 146a, 155, 199a, and 221, were determined by quantitative real time polymerase chain reaction; CEC, by semi-automated immunomagnetic; and plasma angiogenic proteins, by enzyme linked immunosorbent assays.
RESULTS
Levels of miR-199a were positively correlated and miR-106a negatively correlated with CEC pre-therapy. Decreases in miR-126 and miR-199a and increases in miR-16 and miR-106a were observed after interferon-alfa-2b, but not after dacarbazine. CEC also increased after treatment with interferon but not after treatment with dacarbazine. Levels of miRs did not correlate with levels of vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8. Angiogenic proteins also did not change significantly with treatment.
CONCLUSIONS
Blood levels of specific angioregulatory miRs are associated with CEC, and changes in specific angioregulatory miRs parallel increases in CEC after treatment with interferon-alfa-2b. Blood levels of specific angioregulatory miRs are not associated with levels of angiogenic proteins. miRs warrant further evaluation as blood biomarkers of angiogenesis.
背景
需要血液生物标志物来监测癌症的抗血管生成治疗。本研究旨在探讨接受具有抗血管生成活性药物治疗的患者血液中与血管生成相关的 microRNAs（miRs）与循环内皮细胞（CEC）和血管生成蛋白的相关性。
方法
采集葡萄膜黑色素瘤患者的血液，这些患者参加了一项辅助治疗试验，他们先后接受达卡巴嗪和干扰素-α-2b 治疗。通过实时定量聚合酶链反应（PCR）测定血浆中 9 种血管调节 miR（miR-16、20a、106a、125b、126、146a、155、199a 和 221）的水平；通过半自动免疫磁珠法测定 CEC；通过酶联免疫吸附试验（ELISA）测定血浆血管生成蛋白。
结果
miR-199a 的水平与治疗前的 CEC 呈正相关，miR-106a 与 CEC 呈负相关。干扰素-α-2b 治疗后观察到 miR-126 和 miR-199a 降低，miR-16 和 miR-106a 增加，但达卡巴嗪治疗后无此改变。干扰素治疗后 CEC 也增加，但达卡巴嗪治疗后无此改变。miR 水平与血管内皮生长因子、碱性成纤维细胞生长因子和白细胞介素-8 的水平无关。治疗后血管生成蛋白也没有明显变化。
结论
特定的血管生成调节 miR 的血液水平与 CEC 相关，并且在干扰素-α-2b 治疗后，特定的血管生成调节 miR 的变化与 CEC 的增加平行。特定的血管生成调节 miR 的血液水平与血管生成蛋白的水平无关。miR 作为血管生成的血液生物标志物值得进一步评估。
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