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ENHANCED BURKITT’S LYMPHOMA CELL KILLING BY THE COMBINATION TREATMENTS OF BORTEZOMIB WITH CELECOXIB AND 2,5-DIMETHYL-CELECOXIB (DMC)
by
Szu-Ting Chen
___________________________________________________
A Thesis Presented to the
FACULTY OF GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
May 2008
Copyright 2008 Szu-Ting Chen
Object Description
| Title | Enhanced Burkitt 's lymphoma cell killing by the combination treatments of bortezomib with celecoxib and 2,5-dimethyl-celecoxib (DMC) |
| Author | Chen, Szu-Ting |
| Author email | szutingc@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-03-28 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-04-16 |
| Advisor (committee chair) | Tokes, Zoltan |
| Advisor (committee member) |
Schonthal, Axel Hong, Young |
| Abstract | Cell death induced by endoplasmic reticulum (ER) stress response (ESR) mechanism has been implicated in many diseases. The proteasome inhibitor bortezomib (Velcade®) is known to cause ESR via the accumulation of obsolete and damaged proteins. The selective cycloxygenase-2 (COX-2) inhibitor, celecoxib (Celebrex®) and its analog, 2,5-dimethyl-celecoxib (DMC) were previously shown to trigger ER stress by inhibiting the sarcoplasmic/ER calcium ATPase (SERCA), which allows leakage of calcium from the ER into the cytosol. We hypothesized that the combination of two ER stress-triggering drugs, bortezomib and DMC/celecoxib, would increase ESR substantially and greatly enhance their anti-tumor efficiency in Burkitt 's lymphoma cell. With the use of Raji cells, we have examined an elevated level of ER stress marker CHOP/GADD153, apoptotic marker PARP-1, and a significant cell growth reduction in the treatment of bortezomib with celecoxib/DMC. Hence, we propose the treatments of bortezomib with DMC and celecoxib as effective combinations to enhance Burkitt 's lymphoma cell killing in vitro. |
| Keyword | Burkitt's lymphoma; celecoxib; 2,5-dimethyl-celecoxib |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1137 |
| Rights | Chen, Szu-Ting |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Chen-20080416 |
| Archival file | uscthesesreloadpub_Volume44/etd-Chen-20080416.pdf |
Description
| Title | Page 1 |
| Full text | ENHANCED BURKITT’S LYMPHOMA CELL KILLING BY THE COMBINATION TREATMENTS OF BORTEZOMIB WITH CELECOXIB AND 2,5-DIMETHYL-CELECOXIB (DMC) by Szu-Ting Chen ___________________________________________________ A Thesis Presented to the FACULTY OF GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOCHEMISTRY AND MOLECULAR BIOLOGY) May 2008 Copyright 2008 Szu-Ting Chen |
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