Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 98-130) Also available in print.

published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Metastasis is the most fearsome aspect of breast cancer (BC) a common disease in women, because it drives mortality. Although BC can invade almost any organ, it is most often found to invade the bone (31-79%), the brain (3-12%), the liver (8-18%) and the lung (11-13%). The site of distant metastasis is often associated with cause of death and length of survival. This dissertation examines whether the presence of select lifestyle and clinical factors can predict metastatic spread to the lung and/or the liver for a particular woman with advanced breast cancer. A systematic review of the literature identified tobacco use as a risk factor for lung metastasis in women with BC and suggested that obesity, hormone replacement therapy prior to BC diagnosis, hormonal therapy post diagnosis, and post-mastectomy radiation therapy may have an impact on this association. The review also uncovered that liver disease (i.e. hepatic steatosis, chronic hepatitis B infection, cirrhosis) is associated with the occurrence of liver metastasis in patients with colorectal cancer and that hyperglycemic and oxidative stress conditions as well as alcohol consumption were found to be associated with liver metastasis in colorectal or BC patients. We conducted a retrospective hospital-based case-control study of the association of select lifestyle and clinical factors with metastases detected in the lung and the liver among women diagnosed with stages II-IV BC and seen at the Columbia University Medical Center from 2008 to 2013. Select relevant clinical variables were extracted from the hospital patient charts and lifestyle factors from patients’ responses to a questionnaire developed for the purposes of this research. We examined whether smoking and / or post-mastectomy radiation therapy to the breast and/or the chest area were associated with an increased risk of 1st site lung metastasis in our sample of women with metastatic BC. We found that lifestyle factors such as smoking history or BMI at diagnosis did not affect the likelihood of 1st site lung metastasis in our sample of women. We also investigated whether a history of alcohol intake or chronic liver disease was associated with risk of developing a 1st site liver metastasis. Our analyses suggested that lifestyle factors such as alcohol intake or obesity might not affect the likelihood of 1st site liver metastasis in women with metastatic BC. We also report that a history of chronic liver disease significantly increased the odds of 1st site liver metastasis. Given our findings around adjuvant post mastectomy radiation therapy and chronic liver disease, we suggest collecting adjuvant treatment or relevant comorbid information in larger cohort studies. A better understanding of the relationship between these factors and the sites of metastasis has the potential to increase our understanding of the metastatic process. If we can find ways to identify women at high risk of metastatic disease, or develop preventive or therapeutic measures against lung or liver metastasis, we can hope to reduce mortality from metastases.

Magnetic resonance imaging (MRI) is the leading imaging technique for disease diagnostics. MRI contrast agents facilitate MRI technique to obtain tissue-specific image with improved sensitivity and signal-to-noise ratio. However, the applications of current MRI contrast agents are hampered by their uncontrolled blood circulation time, low relaxivity, and low specificity. To address such need, I have developed a series of analitical methods to determine and evaluate the strong metal binding affinity and metal selectivity of developed protein-based contrast agents (ProCAs). In addition, we have successed designed contrast agents ProCA3 series based on key determinats for metal binding sites and relaxivity. We have dementrated that one of the ProCA3 variants, ProCA32, has a high Gd3+ affinity less than 10-21 M and high metal selectivity with relxivity of more than 30 mM-1s-1 per Gd and 60 mM-1s-1 per particle. Moreover, we have demonstrated that ProCA3 variants have proper blood circulation time, high relaxivity, high metal selectivity and low toxicity, which facilitate MR imaging of multiple organs, such as liver, kidney, and blood vessels, as well as tumors. ProCA32 is also able to image liver metastases a tumor size less than 0.25 mm, which is more than fourty times more sensitive than that of clinical diagnostics of liver metastases using MRI and our developed methodology. We have further created ProCA3 variants with targeting peptide moieties such as ProCA3.bomb or ProCA3.affi to against cancer biomarkers such as GRPR and HER2 with capability to imaging tumor biomarker expressions in vivo at molecular level. We have shown that ProCA3 has an excellent safety profile and pharmacokinetics for MRI in animals. With our additional effect in protein expression, modification, and scale up production of these developed protein contrast agents, ProCA3 is expected to be a promising MRI contrast for the diagnostics for disease, such as metastatic tumor and blood vessel abnormalities, and tumor biomarkers.

published_or_final_version / Medicine / Master / Doctor of Medicine

published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18127号 / 医博第3847号 / 新制||医||1001(附属図書館) / 30985 / 京都大学大学院医学研究科医学専攻 / (主査)教授 千葉 勉, 教授 松田 道行, 教授 野田 亮 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Radyodiagnostik Anabilim Dalı, 2004. / Bibliyografya var.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19587号 / 医博第4094号 / 新制||医||1014(附属図書館) / 32623 / 京都大学大学院医学研究科医学専攻 / (主査)教授 松原 和夫, 教授 妹尾 浩, 教授 浅野 雅秀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM