微气泡
医学
卵巢癌
组织因子
体内
癌症研究
病理
浆液性液体
超声波
卵巢癌
恶性肿瘤
癌症
内科学
生物
放射科
生物技术
凝结
作者
Meghan M. Newcomer,Kalpana Deepa Priya Dorayappan,Vincent Wagner,Adrian A. Suarez,Corinne Calo,Eileen Kalmar,G. Larry Maxwell,David M. O’Malley,David E. Cohn,Michael F. Tweedle,Karuppaiyah Selvendiran
标识
DOI:10.1016/j.ygyno.2023.04.008
摘要
Introduction Ovarian cancer (OC) is the deadliest gynecologic malignancy, with an overall 5-year survival rate of less than 30%. The existing paradigm for OC detection involves a serum marker, CA125, and ultrasound examination, neither of which is sufficiently specific for OC. This study addresses this deficiency through the use of a targeted ultrasound microbubble directed against tissue factor (TF). Methods TF expression was examined in both OC cell lines and patient-derived tumor samples via western blotting and IHC. In vivo microbubble ultrasound imaging was analyzed using high grade serous ovarian carcinoma orthotopic mouse models. Results While TF expression has previously been described on angiogenic, tumor-associated vascular endothelial cells (VECs) of several tumor types, this is first study to show TF expression on both murine and patient-derived ovarian tumor-associated VECs. Biotinylated anti-TF antibody was conjugated to streptavidin-coated microbubbles and in vitro binding assays were performed to assess the binding efficacy of these agents. TF-targeted microbubbles successfully bound to TF-expressing OC cells, as well as an in vitro model of angiogenic endothelium. In vivo, these microbubbles bound to the tumor-associated VECs of a clinically relevant orthotopic OC mouse model. Conclusion Development of a TF-targeted microbubble capable of successfully detecting ovarian tumor neovasculature could have significant implications towards increasing the number of early-stage OC diagnoses. This preclinical study shows potential for translation to clinical use, which could ultimately help increase the number of early OC detections and decrease the mortality associated with this disease.
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