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BLOCKADE OF CXCR2 AS A NOVEL APPROACH FOR CANCER CHEMOTHERAPY
by
Nidhi Sharda
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(PHARMACEUTICAL SCIENCES)
May 2012
Copyright 2012 Nidhi Sharda
Object Description
| Title | Blockade of CXCR2 as a novel approach for cancer chemotherapy |
| Author | Sharda, Nidhi |
| Author email | sharda@usc.edu;ms.nidhisharda@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2012-05-08 |
| Date submitted | 2012-05-08 |
| Date approved | 2012-05-09 |
| Restricted until | 2012-05-09 |
| Date published | 2012-05-09 |
| Advisor (committee chair) | Louie, Stan |
| Advisor (committee member) |
Duncan, Roger Olenyuk, Bogdan |
| Abstract | There is interplay between the malignant tumor cells and their non-malignant counterparts found in the microenvironment. This active bi-directional cross-talk between cancer cells and normal host cells has profound implications for tumor survival, proliferation and progression. Chemokines play a key role in cancer related inflammation and angiogenesis. Several evidences in chemokine system reveal that they affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis. Interleukin-8 or IL-8 is the prototype of the angiogenic chemokine family. IL-8 signaling plays a key role in development of tumor microenvironment and cancer progression. Angiogenesis, migration and chronic inflammation are key determinants of the process of tumorigenesis and tumor proliferation. We have used SCH-527123, an anti-inflammatory agent used for the treatment of asthma, as a prototype compound to determine whether this is a good target for anticancer drug development. We assessed growth inhibition and migration by MTT and colony formation assay and wound healing scratch assay in breast cancer cellular model. We studied effect on angiogenesis by tube formation assay on HMEC endothelial cells. We have confirmed anti-angiogenic and anti-migration activity as a consequence of CXCR1/2 receptor blockade, as seen from gene expression data. ❧ In conclusion, our data in the breast cancer model showed that SCH-527123 has potential anti-cancer properties. The cytotoxic activity may be not being linked to its anti-activity since higher concentrations are necessary to achieve IC50. These findings need to be verified in xenograft tumor bearing models.. Future studies in co-culture experiments with neutrophils, condition media, which simulate tumor microenvironment may provide information as to the role of tumor microenvironment in cancer proliferation. |
| Keyword | CXCR2; IL8; Cancer; chemotherapy; inflammation; angiogenesis |
| 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 |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Sharda, Nidhi |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-ShardaNidh-823.pdf |
Description
| Title | Page 1 |
| Full text | BLOCKADE OF CXCR2 AS A NOVEL APPROACH FOR CANCER CHEMOTHERAPY by Nidhi Sharda A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (PHARMACEUTICAL SCIENCES) May 2012 Copyright 2012 Nidhi Sharda |
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