Showing papers by "Setsuko K. Chambers published in 2009"
TL;DR: This autocrine stimulation model using stable transfection of a 4-kb CSF-1 construct into otherwise nonvirulent Bix3 ovarian cancer cells is validated and offers a model by which novel biologic therapies can potentially target multiple levels of this pathway.
56 citations
TL;DR: The evidence to date for the role of CSF-1/c-fms signaling in ovarian cancer invasiveness and metastasis is described, including the recent understanding of how CS fms expression is regulated with identification of significant post-transcriptional regulators.
Abstract: Despite the dismal outcome seen in the majority of epithelial ovarian cancer patients, there is ongoing progress in understanding the disease at a molecular level. Elucidation of pathways underlying disease progression and metastasis of ovarian cancer is key to development of targeted therapeutics. It is only in this way that therapeutic potential can be translated to reality. Here, we describe the evidence to date for the role of CSF-1/c-fms signaling in ovarian cancer invasiveness and metastasis, including the recent understanding of how CSF-1/c-fms expression is regulated with identification of significant post-transcriptional regulators.
53 citations
TL;DR: HuR plays a supportive role for c-fms in breast cancer progression by binding a 69-nt element in its 3′UTR, thus regulating its expression, and is the first to describe that HuR can regulate gene expression by binding non-AU-rich sequences in 3′utR c- fms RNA.
Abstract: The role of RNA-binding proteins in cancer biology is recognized increasingly. The nucleocytoplasmic shuttling and AU-rich RNA-binding protein HuR stabilizes several cancer-related target mRNAs. The proto-oncogene c-fms, whose 3'untranslated region (3'UTR) is not AU-rich, is associated with poor prognosis in breast cancer. Using a large breast-cancer tissue array (N=670), we found nuclear HuR expression to be associated with nodal metastasis and independently with poor survival (P=0.03, RR 1.45), as well as to be co-expressed with c-fms in the breast tumors (P=0.0007). We described c-fms mRNA as a direct target of HuR in vivo, and that HuR bound specifically to a 69-nt region containing 'CUU' motifs in 3'UTR c-fms RNA. Overexpressing or silencing HuR significantly up- or down-regulated c-fms RNA expression, respectively. We also found that known glucocorticoid stimulation of c-fms RNA and protein is largely dependent on the presence of HuR. HuR, by binding to the 69-nt wild type, but not mutant, c-fms sequence can regulate reporter gene expression post-transcriptionally. We are the first to describe that HuR can regulate gene expression by binding non-AU-rich sequences in 3'UTR c-fms RNA. Collectively, our findings suggest that HuR plays a supportive role for c-fms in breast cancer progression by binding a 69-nt element in its 3'UTR, thus regulating its expression.
37 citations
TL;DR: Although a meta-analysis of 53 studies including those using modern chemotherapeutic agents demonstrated that greater primary surgical cytoreduction significantly increases median survival of ovarian cancer, it is unlikely that any further advances in surgical technology will significantly impact patient survival.
Abstract: Epithelial ovarian cancer is the leading cause of gynecologic cancer death among developed nations worldwide and is the fifth leading cause of overall cancer mortality among women in the United States. Despite the high mortality rates, ovarian cancer has a relatively low prevalence (0.075% of the U.S. female population). For women with regional and distant disease, the 5-year survival rates are 69% and 30%, respectively. Themajority of women diagnosed with ovarian cancer (approximately 75%) present with advanced-stage disease. Barriers to developing effective screening programs for ovarian cancer include its relatively low prevalence; lack of specific clinical symptoms; and that the cell of epithelial cancer origin is not clear with lack of a well-defined molecular precursor. Most ovarian cancer diagnoses (approximately 90%) are sporadic, and the remaining 10% are hereditary (e.g., primarily related to BRCA1/2 mutations). There are no known, specific, validated biomarkers to date that could be used for early detection among those at high risk for ovarian cancer. Although a meta-analysis of 53 studies including those using modern chemotherapeutic agents demonstrated that greater primary surgical cytoreduction significantly increases median survival of ovarian cancer, it is unlikely that any further advances in surgical technology will significantly impact patient survival. However, surgical improvements are needed to further reduce surgical complications, to improve patient quality of life, and to ensure that as many patients as possible are optimally debulked. Thus, the pursuit of new therapeutics is of utmost importance if advancements are to be made in the survival of ovarian cancer. In the 1990s, the combination of intravenous platinum plus a taxane became the standard of care based on phase III studies done by the Gynecologic
10 citations