Browsing by Subject "breast"
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Item Engineering functionalized gold nanoparticles as a molecular-specific contrast agent to enhance optoacoustic detection of breast cancer cells(2008-12-02) Mohammad Eghtedari; Massoud Motamedi; Vicente Resto; Nicholas A Kotov; Malcolm Brodwick; Gracie VargasMolecular targeting of malignant tumors is a promising field of research that could potentially revolutionize the diagnosis and treatment of many types of cancer including breast. Delivering molecular specific contrast agents to breast cancer cells would enhance the sensitivity and specificity of imaging methods to detect cancer foci at earlier stages, when complete cure is possible. Optoacoustic tomography (OAT) is a non-invasive imaging modality that can be used to produce an image of the distribution of light absorbing components deep within a turbid medium such as human breast. OAT could potentially be used to image breast tumors based on their enhanced angiogenesis; however, its sensitivity and specificity would be limited due to the lack of abnormal angiogenesis at the early stages of tumor growth.\r\nGold nanoparticles generate strong acoustic signal upon pulse laser irradiation and thus are detectable at low concentrations using optoacoustic technique. The goal of this dissertation is to engineer functionalized gold nanoparticles and employ them as a contrast agent for optoacoustic detection of cancer cells.\r\nTo achieve this goal: 1) gold nanoparticles were fabricated in different shape and sizes and their physicochemical properties were optimized for both tumor targeting and optoacoustic detection; 2) the biological properties of fabricated gold nanoparticles were evaluated in vitro and in vivo by determining their stability, toxicity, biodistribution, and molecular targeting properties; 3) the performance of gold nanoparticles to target cancer cells and function as a contrast agent for OAT were assessed in vitro using breast phantoms and then in vivo using animal models.\r\nItem Role of MMP2, MMP3 and MMP9 in the development of breast cancer brain and lung metastasis in a syngeneic rat model(Texas A&M University, 2005-11-01) Mendes, Odete RodriguesIn order to study the expression of MMP2, MMP 3 and MMP9 in breast cancer brain and lung metastasis, we used a syngeneic rat model of distant metastasis of ENU1564, a carcinogen-induced mammary adenocarcinoma cell line. At six weeks post inoculation we observed development of micro-metastasis in the brain and lung. Immunohistochemistry and Western blotting analyses showed that MMP 2, -3 and -9 protein expression is consistently significantly higher in neoplastic brain tissue compared to normal brain tissue. Lung metastases express abundant MMP2, -3 and -9 in neoplastic cell cytoplasm. In situ zymography revealed gelatinase activity within the brain metastasis. Gel zymography showed an increase in MMP2 and MMP3 activity in brain metastasis. Furthermore, we were able to significantly decrease the development of breast cancer brain and lung metastasis in animals by treatment with PD 166793, a selective synthetic MMP inhibitor. In addition, PD 166793 decreased the in vitro invasive cell behavior of ENU1546. TIMP2 overexpression also decreased the development of breast cancer lung metastasis in our model. Our results suggest that MMP2, -3 and -9 may be involved in the process of metastasis of breast cancer to the brain and lung. Because astrocytes have been associated with breast cancer brain metastasis we evaluated the role of astrocytes and ERK2 pathway in MMP2 up-regulation in BC brain metastasis. A significant decrease in brain metastases development, and orthotopic tumor size and weight were observed in animals inoculated with ENU1564-TIMP2 cells. These were associated with decreased MMP2 activity, as demonstrated by gel zymography. Rat astrocyte-conditioned media increased expression of MMP2 in ENU15645 cells and increased in vitro cell invasion of ENU1564 and ENU1564-TIMP2 cells. Blockage of ERK1/2 phosphorylation by treatment with PD98059 decreased the expression of MMP2 in cancer cells grown in rat astrocyte-conditioned media. We determine that MMP2 plays a role in in vivo development of breast cancer brain metastases. Additionally, we conclude that astrocytes are associated with expression of MMP2 in cancer cells via ERK1/2 signaling pathway.