Setsuko K Chambers

Interests

Research

1. CSF-1 and its role in neoplastic progression and metastasis of ovarian cancer; the role of RNA binding proteins and miRNAs in regulation of CSF-1 expression.2. Androgens and neoplastic transformation of normal ovarian surface epithelium.3. The c-fms proto-oncogene and breast cancer invasiveness and bone metastasis; mechanism of regulation of c-fms expression novel c-fms RNA binding proteins and miRNAs.

Courses

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Scholarly Contributions

Journals/Publications

• Woo, H. H., Lee, S. C., Gibson, S. J., & Chambers, S. K. (2017). Expression of the cytoplasmic nucleolin for post-transcriptional regulation of macrophage colony-stimulating factor mRNA in ovarian and breast cancer cells. Biochimica et biophysica acta, 1860(3), 337-348.
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  The formation of the mRNP complex is a critical component of translational regulation and mRNA decay. Both the 5' and 3'UTRs of CSF-1 mRNA are involved in post-transcriptional regulation. In CSF-1 mRNA, a small hairpin loop structure is predicted to form at the extreme 5' end (2-21nt) of the 5'UTR. Nucleolin binds the hairpin loop structure in the 5'UTR of CSF-1 mRNA and enhances translation, while removal of this hairpin loop nucleolin binding element dramatically represses translation. Thus in CSF-1 mRNA, the hairpin loop nucleolin binding element is critical for translational regulation. In addition, nucleolin interacts with the 3'UTR of CSF-1 mRNA and facilitates the miRISC formation which results in poly (A) tail shortening. The overexpression of nucleolin increases the association of CSF-1 mRNA containing short poly (A)n≤26, with polyribosomes. Nucleolin both forms an mRNP complex with the eIF4G and CSF-1 mRNA, and is co-localized with the eIF4G in the cytoplasm further supporting nucleolin's role in translational regulation. The distinct foci formation of nucleolin in the cytoplasm of ovarian and breast cancer cells implicates the translational promoting role of nucleolin in these cancers.
• Chen, H., Klein, R., Arnold, S., Chambers, S., & Zheng, W. (2016). Cytologic studies of the fallopian tube in patients undergoing salpingo-oophorectomy. Cancer cell international, 16, 78.
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  Mounting evidence suggests the fallopian tube as the origin for ovarian high grade serous carcinoma (HGSC). We attempted to identify the tubal cytological features that allow us to distinguish malignant from benign conditions.
• Jones, K. M., Randtke, E. A., Yoshimaru, E. S., Howison, C. M., Chalasani, P., Klein, R. R., Chambers, S. K., Kuo, P. H., & Pagel, M. D. (2016). Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.
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  We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis.
• Sinharay, S., Randtke, E. A., Jones, K. M., Howison, C. M., Chambers, S. K., Kobayashi, H., & Pagel, M. D. (2016). Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI. Magnetic resonance in medicine.
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  We proposed to detect the in vivo enzyme activity of γ-glutamyl transferase (GGT) within mouse models of human ovarian cancers using catalyCEST MRI with a diamagnetic CEST agent.
• Tate, T. H., Baggett, B., Rice, P. F., Koevary, J. W., Orsinger, G. V., Nymeyer, A. C., Welge, W. A., Saboda, K., Roe, D. J., Hatch, K. D., Chambers, S. K., Utzinger, U., & Barton, J. K. (2016). Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early-stage cancer detection. Journal of biomedical optics, 21(5), 56005.
• Wang, X., Li, L., Cragun, J. M., Chambers, S. K., Hatch, K. D., & Zheng, W. (2016). Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 26(5), 918-23.
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  The aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC).
• Wang, Y., Wang, Y., Zhang, Z., Park, J. Y., Guo, D., Liao, H., Yi, X., Zheng, Y., Zhang, D., Chambers, S. K., & Zheng, W. (2016). Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway. Oncotarget, 7(9), 10363-72.
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  Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer.