Person:
McDonald, John F.

Permanent Link
https://hdl.handle.net/1853/72810
Associated Organization(s)
Organizational Unit
ORCID
ArchiveSpace Name Record

Filters

2007 - 2010 4
4
3 1
4
4
Reset filters

Settings
Author: Dickerson, Erin B. ×

Publication Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Chemosensitization of cancer cells by siRNA using targeted nanogel delivery
    (Georgia Institute of Technology, 2010-01-11) Dickerson, Erin B. ; Blackburn, William H. ; Kapa, Laura B. ; Lyon, L. Andrew ; McDonald, John F.
    Background. Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics. Methods. We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated. Results. Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05).
  • Thumbnail Image
    Item
    Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas
    (Georgia Institute of Technology, 2007-05-17) Moreno, Carlos S. ; Matyunina, Lilya V. ; Dickerson, Erin B. ; Schubert, Nina ; Bowen, Nathan J. ; Logani, Sanjay ; Benigno, Benedict B. ; McDonald, John F.
    Gene expression profiles of malignant tumors surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pretreated with chemotherapy prior to surgery (C-L), while the other clusters with non-malignant adenomas (A-L). We show here that although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations, the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships. Our results support a model whereby p53 mediated cell-cycle-arrest/DNA repair serves as a barrier to optimal chemotherapeutic treatment of ovarian and perhaps other carcinomas and suggest that inhibition of p53 during chemotherapy may enhance clinical outcome.
  • Thumbnail Image
    Item
    Emerging Roles for PAX8 in Ovarian Cancer and Endosalpingeal Development
    (Georgia Institute of Technology, 2007-02) Bowen, Nathan J. ; Logani, Sanjay ; Dickerson, Erin B. ; Kapa, Laura B. ; Akhtar, Mariam ; Benigno, Benedict B. ; McDonald, John F.
    Objectives. Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo complex differentiation to form distinguishable phenotypes resembling those of the epithelia of the female urogenital regions. While previous studies have implicated regulatory developmental homeobox (HOX) genes in this process, other factors responsible for this differentiation are largely unknown. Aberrant transcriptional expression of PAX8 has been reported in epithelial ovarian cancer, prompting us to initiate the molecular characterization of this master regulatory gene in ovarian cancer development. Methods. Immunohistochemistry, immunoblotting and RT-PCR were used to investigate the presence of PAX8 and its protein products in epithelial ovarian cancer subtypes, normal ovarian surface epithelia, ovarian inclusion cysts and normal endosalpingeal epithelia. Results. In this report, we confirm microarray results indicating that the transcription factor, PAX8, is highly expressed in epithelial ovarian cancer but absent from the precursor ovarian surface epithelia of healthy individuals. Furthermore, we report that PAX8 is localized to the nucleus of non-ciliated epithelia in simple ovarian epithelial inclusion cysts and in three epithelial ovarian cancer subtypes (serous, endometrioid and clear cell). We also determined that PAX8 is expressed in the non-ciliated, secretory cells of healthy fallopian tube mucosal linings but not in the adjacent ciliated epithelia. Conclusion. These findings support the hypothesis that PAX8 plays parallel roles in the development of epithelial ovarian cancer and in the developmental differentiation of coelomic epithelia into endosalpingeal epithelia.
  • Thumbnail Image
    Item
    Identification of candidate methylation-responsive genes in ovarian cancer
    (Georgia Institute of Technology, 2007-01-25) Menendez, Laura ; Walker, L. DeEtte ; Matyunina, Lilya V. ; Dickerson, Erin B. ; Bowen, Nathan J. ; Benigno, Benedict B. ; McDonald, John F.
    Background: Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs) are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers. Results: In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3) before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC). An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, > 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified. Conclusion: We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.