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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Zayzafoon, Majd"). Showing records 1 – 2 of 2 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 January 23, 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. 23 Jan 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 Jan 23]. 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. Ashley, Jason Waid. Significance and regulation of CD68 expression in the osteoclast.

Degree: PhD, 2011, University of Alabama – Birmingham

The mucin-like Lysosome Associated Membrane Protein (LAMP) family member CD68 is a primarily myeloid lineage restricted transmembrane protein that is expressed in macrophages and osteoclasts. While the existence and expression pattern of human CD68 and mouse CD68 (sometimes called macrosialin) are well-known, and these molecules are routinely used as histological markers of tissue macrophages, the functional significance of CD68 expression remains an unanswered question. Our overall goal is to determine the significance and characterize the function of CD68 in osteoclasts and explore the effects of Receptor Activator of Nuclear Factor κB (RANK) signaling on CD68 posttranslational modification. To achieve this goal, I used homologous recombination to generate a mouse line that lacks expression of CD68. Mice that lack CD68 expression have increased trabecular bone and dysfunctional, morphologically aberrant osteoclasts demonstrating the importance of CD68 expression for proper osteoclast function. Next, altered glycosylation of CD68 that occurs with RANK ligand (RANKL)-stimulated osteoclastogenesis was investigated. I found that RANKL induces an increase in terminal sialylation of CD68, and this change is dependent upon the signaling of RANK Tumor Necrosis Factor Associated Factor (TRAF) binding motifs 539PVQEET564 and 604PVQEQG609 and the non-TRAF motif 535IVVY538 perhaps through the action of the sialating enzyme ST3Gal1. Finally, I developed an assay to identify inhibitors of the sig-naling from 539PVQEET564 and 604PVQEQG609. In addition to contributing to the RANKL-induced modification of CD68, these signaling motifs are also necessary for the normal formation of osteoclasts, and inhibitors of these motifs may serve as valuable new anti-resorptive therapeutics. Importantly, the work of this dissertation establishes CD68 as an important molecule for osteoclast function and marks it as a potential therapeutic target for treating disorders of bone loss. In addition, this work should open new avenues of research into functions of CD68 and the significance of its RANKL-induced alterna-tive glycosylation.

1 online resource (xi, 144 p.) : ill., digital, PDF file.

Joint Health Sciences;

Osteoclast Bone CD68 Osteoporosis

UNRESTRICTED

Advisors/Committee Members: Feng, Xu, Welch, Danny R.<br>, Bellis, Susan<br>, Busby, J. Erik<br>, Murphy-Ullrich, Joanne<br>, Zayzafoon, Majd.

Subjects/Keywords: Antigens, CD  – genetics<; br>; Antigens, Differentiation, Myelomonocytic  – genetics<; br>; Biological Assay  – methods<; br>; Bone and Bones<; br>; Drug Evaluation, Preclinical  – methods<; br>; Gene Deletion<; br>; High-Throughput Screening Assays  – methods<; br>; Macrophages  – drug effects<; br>; Osteoclasts<; br>; Receptor Activator of Nuclear Factor-kappa B  – metabolism<; br>; Signal Transduction  – physiology

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

APA (6th Edition):

Ashley, J. W. (2011). Significance and regulation of CD68 expression in the osteoclast. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1033

Chicago Manual of Style (16th Edition):

Ashley, Jason Waid. “Significance and regulation of CD68 expression in the osteoclast.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed January 23, 2020. http://contentdm.mhsl.uab.edu/u?/etd,1033.

MLA Handbook (7th Edition):

Ashley, Jason Waid. “Significance and regulation of CD68 expression in the osteoclast.” 2011. Web. 23 Jan 2020.

Vancouver:

Ashley JW. Significance and regulation of CD68 expression in the osteoclast. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2020 Jan 23]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1033.

Council of Science Editors:

Ashley JW. Significance and regulation of CD68 expression in the osteoclast. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1033

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