The association of blood angioregulatory microRNA levels with circulating endothelial cells and angiogenic proteins in p
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RESEARCH
Open Access
The association of blood angioregulatory microRNA levels with circulating endothelial cells and angiogenic proteins in patients receiving dacarbazine and interferon Pierre L Triozzi1*, Susan Achberger1, Wayne Aldrich1, Arun D Singh2, Ronald Grane1 and Ernest C Borden1
Abstract 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. Keywords: Biomarker, Tumor angiogenesis, Vascular endothelial growth factor, Basic fibroblast growth factors, Interleukin-8, Melanoma
Background A number of drugs with anti-angiogenic effects are in common use to treat cancer, and a number are under investigation. Although many methods have been tested in preclinical and clinical studies, there are no established methods of serially monitoring patients receiving antiangiogenic therapies. Several studies have focused on known protein mediators of angiogenic processes. * Correspondence: [email protected] 1 Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA Full list of author information is available at the end of the article
Changes in blood levels of, e.g., vascular endothelial growth factor (VEGF), basic fibroblast growth factors (bFGF), and interleukin- (IL-) 8, have been observed in response to anti-angiogenic drugs. The results have been conflicting, due in part to the different clinical situations investigated. Their use may also be confounded by increases ass
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