Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer
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2020
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu15949750314961732021-08-03T07:15:42Z Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer Flannery , Meghan Maureen Biomedical Research Oncology Pathology Anatomy and Physiology ovarian cancer targeted ultrasound tissue factor Ovarian cancer is the deadliest gynecologic malignancy. While manageable, and even curable if detected during early-stage disease, most patients are undiagnosed until late-stage, at which point, the 5-year survival rate is less than 30%. Although early detection is key for improving survival, there is no accurate screening tool available and current diagnostic modalities lack specificity for early disease. Transvaginal ultrasound, the imaging gold standard for routine examination of ovarian masses, is deficient in its ability to differentially detect malignancy. This study seeks to address this deficiency through a novel diagnostic modality known as targeted ultrasound. Targeted ultrasound involves the use of contrast agents detectable by ultrasound. These agents are micron-size, gas-filled bubbles stabilized by an outer shell to which cancer-specific targeting ligands are conjugated. Microbubbles are injected intravenously where they travel systemically and bind to their target of interest expressed on vascular endothelial cells (VECs). Tissue factor (TF) is a unique, tumor-specific marker expressed in many different cancers, including ovarian. TF expression has also been described on the VECs of tumor-associated vessels, and is associated with angiogenesis – an early event in tumor growth and progression. Based upon this unique, tumor-specific expression profile, the hypothesis of this study is that ovarian cancer can be detected in early-stage disease using a novel, TF-targeting ultrasound microbubble to detect tumor angiogenesis. This study is the first to describe TF expression on ovarian tumor-associated VECs. Additionally, TF-targeted microbubbles were shown to differentially bind to TF-expressing targets, both in vitro and in vivo. The findings of this study establish a foundation for furthering this research to more thoroughly validate TF as an early ovarian cancer biomarker and to examine the potential for clinical translation of TF-targeted microbubbles. 2020-11-06 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1594975031496173 http://rave.ohiolink.edu/etdc/view?acc_num=osu1594975031496173 restricted--full text unavailable until 2025-08-25 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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language |
English |
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topic |
Biomedical Research Oncology Pathology Anatomy and Physiology ovarian cancer targeted ultrasound tissue factor |
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Biomedical Research Oncology Pathology Anatomy and Physiology ovarian cancer targeted ultrasound tissue factor Flannery , Meghan Maureen Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer |
author |
Flannery , Meghan Maureen |
author_facet |
Flannery , Meghan Maureen |
author_sort |
Flannery , Meghan Maureen |
title |
Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer |
title_short |
Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer |
title_full |
Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer |
title_fullStr |
Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer |
title_full_unstemmed |
Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer |
title_sort |
development of a tissue factor-targeted ultrasound microbubble for early detection of ovarian cancer |
publisher |
The Ohio State University / OhioLINK |
publishDate |
2020 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1594975031496173 |
work_keys_str_mv |
AT flannerymeghanmaureen developmentofatissuefactortargetedultrasoundmicrobubbleforearlydetectionofovariancancer |
_version_ |
1719457588990443520 |