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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Zinn, Kurt R."). Showing records 1 – 3 of 3 total matches.

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1. Khotskaya, Yekaterina B. Role of syndecan-1 as key regulator of multiple myeloma pathogenesis.

Degree: PhD, 2009, University of Alabama – Birmingham

Syndecan-1 (CD138), a transmembrane heparan sulfate-bearing proteoglycan, is expressed at high levels on most myeloma cells and is shed into the microenvironment. In patients, high levels of serum syndecan-1 are indicative of poor prognosis and elevation of shed syndecan-1 in animal models dramatically enhances tumor growth, angiogenesis and metastasis. Because syndecan-1 is a key regulator of myeloma pathogenesis, we hypothesized that reduction of syndecan-1 levels expressed by the myeloma cells will block their growth and dissemination. Syndecan-1 knockout and knockdown variants of two human myeloma cell lines, CAG and RPMI-8226, were developed using short hairpin RNA (shRNA) technology. In vitro, knock out of syndecan-1 from the myeloma cell surface resulted in a loss of cell viability via initiation of apoptosis. In contrast, syndecan-1 knockdown cells expressing 14-28% normal syndecan-1 levels were phenotypically similar to the control cells and did not reveal significant growth differences when compared to the control cells in vitro. In contrast, when these knockdown cells were injected into severe combined immunodeficient (SCID) mice in vivo, they formed tumors poorly as compared to cells expressing wild-type levels of syndecan-1. Tumor immunohistology revealed that the VEGF levels were dramatically lower in the knockdown tumors as compared to the controls. Moreover, knockdown of syndecan-1 resulted in grossly underdeveloped vasculature in these tumors. Importantly, most syndecan-1 knockdown cells also failed to grow when injected intravenously into SCID mice, suggesting that post-intravasation steps of the metastatic cascade may be syndecan-1 dependent. Few tumors that arose from knockdown cells in animals injected intravenously formed at extra-osseous sites, further implicating syndecan-1 as a critical molecule for homing of myeloma cells to bone. Taken together, these results indicate that syndecan-1 expression is required for robust myeloma tumor development and growth in vivo via regulation of angiogenesis and metastasis, and that therapies aimed at reducing expression of this proteoglycan may benefit myeloma patients.

1 online resource (xi, 114 p. : ill., digital, PDF file)

Pathology

Joint Health Sciences

Multiple myeloma syndecan-1 angiogenesis heparan sulfate proteoglycan metastasis

UNRESTRICTED

Advisors/Committee Members: Sanderson, Ralph D., Lopez, Richard<br>, Welch, Danny R.<br>, Woods, Anne<br>, Zayzafoon, Majd<br>, Zinn, Kurt R..

Subjects/Keywords: Gene Expression Regulation, Neoplastic<; br>; Melanoma  – metabolism<; br>; Neoplasm Proteins  – biosynthesis<; br>; Neovascularization, Pathologic  – metabolism<; br>; Syndecan-1  – biosynthesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Khotskaya, Y. B. (2009). Role of syndecan-1 as key regulator of multiple myeloma pathogenesis. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,766

Chicago Manual of Style (16th Edition):

Khotskaya, Yekaterina B. “Role of syndecan-1 as key regulator of multiple myeloma pathogenesis.” 2009. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,766.

MLA Handbook (7th Edition):

Khotskaya, Yekaterina B. “Role of syndecan-1 as key regulator of multiple myeloma pathogenesis.” 2009. Web. 29 Mar 2020.

Vancouver:

Khotskaya YB. Role of syndecan-1 as key regulator of multiple myeloma pathogenesis. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2009. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,766.

Council of Science Editors:

Khotskaya YB. Role of syndecan-1 as key regulator of multiple myeloma pathogenesis. [Doctoral Dissertation]. University of Alabama – Birmingham; 2009. Available from: http://contentdm.mhsl.uab.edu/u?/etd,766

2. Warram, Jason M. (Jason Morgan). Strategies for combined screening and imaging of breast cancer.

Degree: PhD, 2011, University of Alabama – Birmingham

Successful treatment of breast cancer directly correlates with tumor stage and grade at diagnosis. Early diagnosis leads to a five-year relative survival rate of 96.8% as opposed to only a 22.5% five-year survival rate when diagnosed at late stage. Cancerspecific mechanisms need to be extended to enable cancer detection in an individual patient, in particular, the metastatic burden that currently cannot be assessed by conventional imaging. This approach for cancer detection would remove the biases of patient characteristics, permit immediate diagnostic feedback, improve sensitivity for early detection of small metastatic lesions, and be cost effective. Toward this goal, the cancer-specific diagnostic adenovirus (Ad) vector (Ad5/3-Id1-SEAP-Id1-mCherry) was produced that includes a human secreted embryonic alkaline phosphatase (SEAP) reporter for blood-based screening and a fluorescent reporter (mCherry) for localized imaging. Importantly, the cancer-specific promoter Id1 was selected to drive both reporters due to the correlation between aggressive cancer phenotypes and high Id1 expression. Safety and efficacy issues have limited the use of recombinant Ad for routine clinical applications. To overcome this impediment, ultrasound microbubbles (MB) were developed to improve Ad delivery to the tumor vasculature. This was achieved by targeting the Ad packaged MB to receptors overexpressed in the tumor, namely αVβ3 integrin, P-selectin, and VEGFR2. During in vitro assessment, both SEAP and mCherry reporter expression was shown to correlate with cancer cell phenotype. In a tumorbearing mouse model, SEAP reporter expression was found to be 14-fold over background when as little as 2.5% of tumor cells were infected. Triple-targeted MBs displayed enhanced affinity for tumor vasculature when assessed in vitro and in vivo. Packaging of the targeted MBs with diagnostic Ad was confirmed and the approach was tested in a tumor-bearing mouse model. Groups receiving the targeted Ad packaged MBs displayed a 4-fold increase in SEAP reporter expression over groups receiving equivalent unpackaged Ad dosing. In addition, the mCherry fluorescence reporter was localized in the tumor. Safe delivery of a non-invasive diagnostic reporter system using FDA approved MBs has the potential for immediate application, allowing this diagnostic system to impact populations currently in need of more advanced and sensitive detection modalities.

1 online resource (xi, 111 p. : ill., digital, PDF file)

Pathology

Joint Health Sciences;

breast cancer screening gene therapy microbubbles ultrasound contrast agent adenovirus delivery

UNRESTRICTED

Advisors/Committee Members: Sanderson, Ralph D., Borovjagin, Anton V.<br>, Feng, Xu<br>, Frost, Andra R.<br>, Lopez, Richard D.<br>, Ponnazhagan, Selvarangan<br>, Zinn, Kurt R..

Subjects/Keywords: Adenoviridae  – genetics<; br>; Breast Neoplasms  – diagnosis<; br>; Gene Therapy<; br>; Mass Screening  – methods<; br>; Microbubbles<; br>; Neoplasm Metastasis<; br>; Promoter Regions, Genetic  – genetics<; br>; Vascular Endothelial Growth Factor Receptor-2  – immunology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Warram, J. M. (. M. (2011). Strategies for combined screening and imaging of breast cancer. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,881

Chicago Manual of Style (16th Edition):

Warram, Jason M (Jason Morgan). “Strategies for combined screening and imaging of breast cancer.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,881.

MLA Handbook (7th Edition):

Warram, Jason M (Jason Morgan). “Strategies for combined screening and imaging of breast cancer.” 2011. Web. 29 Mar 2020.

Vancouver:

Warram JM(M. Strategies for combined screening and imaging of breast cancer. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,881.

Council of Science Editors:

Warram JM(M. Strategies for combined screening and imaging of breast cancer. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,881

3. Szafran, April Adams. The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer.

Degree: PhD, 2008, University of Alabama – Birmingham

The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography and SPECT-CT imaging. Through analysis of histologic sections, bioluminescent images, and markers of bone resorption, therapy studies revealed that murine death receptor 5 agonist mTRA8 and its humanized version hTRA8 significantly reduce tumor burden in mice with experimental metastatic lesions in osseous tissues when combined with zoledronic acid. In a second study, mTRA8 resulted in a significant amount of tumor regression in an in vivo model of lung metastasis. From this work we have concluded that Death Receptor 5 agonist therapy is a promising treatment for breast cancer metastasis in animal models of this human disease and should be evaluated in a clinical setting.

1 online resource (xi, 102 p. : ill., digital, PDF file)

Pathology;

Joint Health Sciences;

breast cancer apoptosis molecular imaging metastasis drug therapy

UNRESTRICTED

Advisors/Committee Members: Zinn, Kurt R., Buchsbaum, Donald J.<br>, Feng, Xu<br>, Grubbs, Clinton<br>, Lorenz, Robinna<br>, Selander, Katri.

Subjects/Keywords: Antibodies, Monoclonal  – pharmacology<; br>; Antineoplastic Combined Chemotherapy<; br>; Protocols  – pharmacology<; br>; Bone Neoplasms<; br>; Breast Neoplasms<; br>; Diphosphonates  – pharmacology<; br>; Imidazoles  – pharmacology<; br>; Mammary Neoplasms, Experimental  – pathology<; br>; Receptors, TNF-Related Apoptosis-Inducing Ligand  – agonists

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Szafran, A. A. (2008). The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,927

Chicago Manual of Style (16th Edition):

Szafran, April Adams. “The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer.” 2008. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,927.

MLA Handbook (7th Edition):

Szafran, April Adams. “The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer.” 2008. Web. 29 Mar 2020.

Vancouver:

Szafran AA. The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2008. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,927.

Council of Science Editors:

Szafran AA. The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer. [Doctoral Dissertation]. University of Alabama – Birmingham; 2008. Available from: http://contentdm.mhsl.uab.edu/u?/etd,927

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