Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment

博士 === 國立陽明大學 === 生物醫學影像暨放射科學系暨研究所 === 100 === Breast cancer is the most common malignancy in women in Taiwan, with an estimate of 8,000 new cases diagnosed in 2009. The decline of the mortality depends on earlier detection of disease, curative surgical excision, and improved treatment of disease wi...

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Main Authors: Shuo-Hui Hung, 洪碩徽
Other Authors: Ran-Chou Chen
Format: Others
Language:en_US
Published: 2012
Online Access:http://ndltd.ncl.edu.tw/handle/18974918761669270980
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description 博士 === 國立陽明大學 === 生物醫學影像暨放射科學系暨研究所 === 100 === Breast cancer is the most common malignancy in women in Taiwan, with an estimate of 8,000 new cases diagnosed in 2009. The decline of the mortality depends on earlier detection of disease, curative surgical excision, and improved treatment of disease with individualized adjuvant therapies. The advent of high resolution breast imagings, minimally invasive surgical techniques, and new chemotherapy agents, the morbidity and mortality rates were significant decreased in recent years. Despite advances in breast cancer diagnosis and treatment, several problems need to be further investigated. First, several studies have attempted to analyze available data in order to establish guidelines for the use of tumor markers for breast cancer. The American Society of Clinical Oncology panel still has not recommend monitoring any of these markers for screening, diagnosis, staging, or routine surveillance of patients free of detectable disease. Second, chemotherapy remains as the fundamental approach for many patients with breast cancer. However, it is true that all such therapeutic cytotoxic agents can damage normal, non-cancerous cells and lead to, or contribute to, chemotherapy-induced side effects. Third, the possibilities of operation related complications were reduced; however, significant morbidities such as wound hematoma, wound infection, seroma, and axillary numbness still remain as a great challenge to all breast surgeons. To investigate these problems, we designed a series of studies. In study 1, we applied a fiber-optic biosensor, based on the optical property of localized surface plasmon coupled fluorescence (LSPCF) combined with a sandwich immunoassay, as a tool to study protein-protein interactions. The detection limit of the LSPCF fiber-optic biosensor (LSPCF-FOB) was as low as ~1 pg/mL for protein-protein interactions. In this study, we found that LSPCF-FOB is capable of detecting t-PSA concentration at a few pg/mL in diluted serum and is helpful to differentiate between healthy and breast cancer-bearing women. Additionally, LSPCF-FOB was used to detect preoperative serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) level. The serum HER2 levels of patients with HER2 positive were higher than those with HER2 negative. Therefore, LSPCF-FOB is a highly sensitive and inexpensive assay with potential for early detection, and predicting aggressive behavior of breast cancer. In study 2, we used contrast enhanced ultrasound (CEUS) to monitor ultrasound triggered microbubble destruction (UTMD). Ultrasound-triggered drug loaded microbubble destruction is a promising strategy of target drug delivery to increase local drug concentration at pathologic site while reducing systemic toxicity. We concluded that sonographic signal measured from peripheral vessels is a feasible indicator of systemic microbubble concentration. Based on the concepts of pharmacokinetic, this may be used to quantify ultrasound-triggered microbubble destruction at the target site. In study 3, a new ultrasonically activated scalpel, Harmonic FOCUS (HF), was introduced as an alternative to conventional methods of hemostasis in surgical procedures for breast conserving surgery (BCS) and axillary lymph node dissection (ALND). Traditional electrocautery is associated with significant thermal injury to surrounding tissue during cutting and coagulation. It has been postulated as a factor of the risk of postoperative seroma formation, wound healing, and thermal injury to the adjacent nerve. HF produces high-frequency vibrations within the harmonic frequency range in cutting and coagulating tissues and generates lower temperature elevation and lesser spread of heat in the adjacent tissues in comparison with electrocautery. We discovered that using HF scalpel in BCS and ALND significantly reduced operative time and axillary numbness rate when compared with convention methods. In conclusion, the theory of biomedical imaging provides a tool not only for breast cancer imaging but also for medical and surgical treatment. Merging with pharmacokinetic and immunoassay provides a potential development in breast cancer diagnosis and treatment.
author2 Ran-Chou Chen
author_facet Ran-Chou Chen
Shuo-Hui Hung
洪碩徽
author Shuo-Hui Hung
洪碩徽
spellingShingle Shuo-Hui Hung
洪碩徽
Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment
author_sort Shuo-Hui Hung
title Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment
title_short Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment
title_full Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment
title_fullStr Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment
title_full_unstemmed Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment
title_sort application of localized surface plasmon coupled fluorescence biosensor and ultrasound forbreast cancer diagnosis and treatment
publishDate 2012
url http://ndltd.ncl.edu.tw/handle/18974918761669270980
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spelling ndltd-TW-100YM0057700072015-10-14T04:07:12Z http://ndltd.ncl.edu.tw/handle/18974918761669270980 Application of Localized Surface Plasmon Coupled Fluorescence Biosensor and Ultrasound forBreast Cancer Diagnosis and Treatment 運用侷域表面電漿子耦合螢光生物感知器及超音波於乳癌之診斷與治療 Shuo-Hui Hung 洪碩徽 博士 國立陽明大學 生物醫學影像暨放射科學系暨研究所 100 Breast cancer is the most common malignancy in women in Taiwan, with an estimate of 8,000 new cases diagnosed in 2009. The decline of the mortality depends on earlier detection of disease, curative surgical excision, and improved treatment of disease with individualized adjuvant therapies. The advent of high resolution breast imagings, minimally invasive surgical techniques, and new chemotherapy agents, the morbidity and mortality rates were significant decreased in recent years. Despite advances in breast cancer diagnosis and treatment, several problems need to be further investigated. First, several studies have attempted to analyze available data in order to establish guidelines for the use of tumor markers for breast cancer. The American Society of Clinical Oncology panel still has not recommend monitoring any of these markers for screening, diagnosis, staging, or routine surveillance of patients free of detectable disease. Second, chemotherapy remains as the fundamental approach for many patients with breast cancer. However, it is true that all such therapeutic cytotoxic agents can damage normal, non-cancerous cells and lead to, or contribute to, chemotherapy-induced side effects. Third, the possibilities of operation related complications were reduced; however, significant morbidities such as wound hematoma, wound infection, seroma, and axillary numbness still remain as a great challenge to all breast surgeons. To investigate these problems, we designed a series of studies. In study 1, we applied a fiber-optic biosensor, based on the optical property of localized surface plasmon coupled fluorescence (LSPCF) combined with a sandwich immunoassay, as a tool to study protein-protein interactions. The detection limit of the LSPCF fiber-optic biosensor (LSPCF-FOB) was as low as ~1 pg/mL for protein-protein interactions. In this study, we found that LSPCF-FOB is capable of detecting t-PSA concentration at a few pg/mL in diluted serum and is helpful to differentiate between healthy and breast cancer-bearing women. Additionally, LSPCF-FOB was used to detect preoperative serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) level. The serum HER2 levels of patients with HER2 positive were higher than those with HER2 negative. Therefore, LSPCF-FOB is a highly sensitive and inexpensive assay with potential for early detection, and predicting aggressive behavior of breast cancer. In study 2, we used contrast enhanced ultrasound (CEUS) to monitor ultrasound triggered microbubble destruction (UTMD). Ultrasound-triggered drug loaded microbubble destruction is a promising strategy of target drug delivery to increase local drug concentration at pathologic site while reducing systemic toxicity. We concluded that sonographic signal measured from peripheral vessels is a feasible indicator of systemic microbubble concentration. Based on the concepts of pharmacokinetic, this may be used to quantify ultrasound-triggered microbubble destruction at the target site. In study 3, a new ultrasonically activated scalpel, Harmonic FOCUS (HF), was introduced as an alternative to conventional methods of hemostasis in surgical procedures for breast conserving surgery (BCS) and axillary lymph node dissection (ALND). Traditional electrocautery is associated with significant thermal injury to surrounding tissue during cutting and coagulation. It has been postulated as a factor of the risk of postoperative seroma formation, wound healing, and thermal injury to the adjacent nerve. HF produces high-frequency vibrations within the harmonic frequency range in cutting and coagulating tissues and generates lower temperature elevation and lesser spread of heat in the adjacent tissues in comparison with electrocautery. We discovered that using HF scalpel in BCS and ALND significantly reduced operative time and axillary numbness rate when compared with convention methods. In conclusion, the theory of biomedical imaging provides a tool not only for breast cancer imaging but also for medical and surgical treatment. Merging with pharmacokinetic and immunoassay provides a potential development in breast cancer diagnosis and treatment. Ran-Chou Chen 陳潤秋 2012 學位論文 ; thesis 83 en_US