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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Selander, Katri"). Showing records 1 – 2 of 2 total matches.

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1. Cody, James Joseph. A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer.

Degree: PhD, 2008, University of Alabama – Birmingham

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by inhibiting bone resorption through the action of OPG. We have constructed an armed CRAd (Ad5-[delta]24-sOPG-Fc-RGD) by replacing viral E3B genes with a fusion of the ligand-binding domains of OPG and the Fc portion of human IgG1, for improved secretion. Conditional replication is conferred by a 24 base pair deletion within E1A ([delta]24), which prevents the binding of E1A to cellular Rb and limits replication in normal cells. The incorporation of an RGD peptide sequence within the fiber knob confers transductional selectivity by directing infection to cells expressing [alpha]v integrins. A panel of control viruses has also been constructed. We first confirmed the expression of sOPG-Fc and the remaining E3 genes from our experimental viruses, and showed that expression from E3B inhibits neither the oncolytic potency nor the selectivity of replication of an RGD-modified CRAd. We demonstrated that infection of breast cancer cells by Ad-[delta]24-sOPG-Fc-RGD both kills the infected cells by oncolysis and inhibits the formation of osteoclasts in an in vitro co-culture model. The efficacy of Ad-[delta]24-sOPG-Fc-RGD was evaluated in a model of breast cancer bone metastasis in which athymic mice are injected intratibially with human breast cancer cells stably expressing luciferase, allowing the progression of osteolytic lesions to be monitored in live animals. The results of these studies demonstrated that our armed CRAd reduces tumor burden in the bone and inhibits osteoclast formation more effectively than an unarmed CRAd. We have therefore shown the enhanced therapeutic efficacy of the dual-action, armed CRAd in treating bone metastases of breast cancer.

xiv, 118 p. :$bill., digital, PDF file.

Pathology

Joint Health Sciences

conditionally replicating adenovirus bone metastasis breast cancer osteoprotegerin virotherapy gene therapy

UNRESTRICTED

Advisors/Committee Members: Douglas, Joanne T., Curiel, David T. <br>, Selander, Katri <br>, Siegal, Gene P. <br>, Welch, Danny R..

Subjects/Keywords: Adenoviridae  – genetics <; br>; Bone Neoplasms  – secondary <; br>; Breast Neoplasms <; br>; Gene Expression Regulation, Neoplastic <; br>; Neoplasm Metastasis  – genetics <; br>; Neoplasm Metastasis  – therapy <; br>; Virus Replication  – genetics

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

APA (6th Edition):

Cody, J. J. (2008). A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,320

Chicago Manual of Style (16th Edition):

Cody, James Joseph. “A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer.” 2008. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,320.

MLA Handbook (7th Edition):

Cody, James Joseph. “A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer.” 2008. Web. 29 Mar 2020.

Vancouver:

Cody JJ. A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2008. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,320.

Council of Science Editors:

Cody JJ. A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer. [Doctoral Dissertation]. University of Alabama – Birmingham; 2008. Available from: http://contentdm.mhsl.uab.edu/u?/etd,320

2. 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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