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Full-Text Articles in Medicine and Health Sciences
Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie
Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie
Donghai Dai
Endometrial cancer is the most frequent gynecologic cancer in women. Long-term outcomes for patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our study was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin, a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting …
A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie
A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie
Donghai Dai
Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase …
Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai
Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai
Donghai Dai
Endometrial cancer (ECa) is the fourth most common malignancy in women. Currently, there is no effective therapy for advanced and recurrent cancer. Among the poor-outcome endometrial cancers, there is a high frequency of TP53 mutations. We have previously reported that amifostine has a direct anti-cancer effect and has a significant synergistic effect with paclitaxel when used in endometrial cancer cell and xenograft models. In this report, using a cell line with knock-down p53 expression through siRNA, we found that amifostine enhancement of paclitaxel's anticancer effect is p53 status-dependent. Amifostine promotes entry into the G2-M phase through regulation of cyclin-dependent kinase-1 …
Progesterone Receptor Isoform Identification And Subcellular Localization In Endometrial Cancer, Kimberly Leslie, M. Stein, N. Kumar, Donghai Dai, J. Stephens, A. Wandinger-Ness, D. Glueck
Progesterone Receptor Isoform Identification And Subcellular Localization In Endometrial Cancer, Kimberly Leslie, M. Stein, N. Kumar, Donghai Dai, J. Stephens, A. Wandinger-Ness, D. Glueck
Donghai Dai
OBJECTIVE: These studies were undertaken to characterize the subcellular localization of the two major isoforms of progesterone receptors (PR), PRA and PRB, in endometrial cancer. METHODS: Immunohistochemistry, immunoprecipitation, and confocal microscopy were performed using Hec50co and KLE endometrial cancer cell models expressing PRA or PRB as a consequence of transduction. The location of PRB compared to PRA was determined, and antibodies were tested for specificity with respect to PR isoform recognition. Immunohistochemical analyses of PR expression and subcellular compartmentalization were also performed on 20 formalin-fixed endometrial cancer tumors. RESULTS: Morphological and biochemical evaluations demonstrated that PRA is localized to the …
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Donghai Dai
OBJECTIVE: Nuclear factor kappa B (NFkappaB) is a strong anti-apoptotic factor, which is constitutively active in human endometrial cancer cells. Progesterone is the principal growth inhibitory hormone in the endometrial epithelium and promotes apoptosis. To identify the pathways through which progesterone controls NFkappaB function, we explored its genomic and non-genomic effects in endometrial cancer cells. METHODS: PR-negative Hec50co endometrial cancer cells were engineered to express high levels of the A or B isoform of PR (PRA or PRB) by adenoviral infection. Cells were treated with progesterone or vehicle alone, and RNA was isolated. Affymetrix microarrays were performed and transcriptional control …
Preclinical Development Of A Neutral, Estrogen Receptor-Targeted, Tridentate 99mtc(I)-Estradiol-Pyridin-2-Yl Hydrazine Derivative For Imaging Of Breast And Endometrial Cancers, T. Nayak, H. Hathaway, C. Ramesh, J. Arterburn, Donghai Dai, L. Sklar, J. Norenberg, E. Prossnitz
Preclinical Development Of A Neutral, Estrogen Receptor-Targeted, Tridentate 99mtc(I)-Estradiol-Pyridin-2-Yl Hydrazine Derivative For Imaging Of Breast And Endometrial Cancers, T. Nayak, H. Hathaway, C. Ramesh, J. Arterburn, Donghai Dai, L. Sklar, J. Norenberg, E. Prossnitz
Donghai Dai
Breast and endometrial cancers are the most common invasive malignancies in women, with more than 217,000 new diagnoses per year in the United States. These cancers are often classified into 2 subtypes based on the expression of the classical estrogen receptor. In this study, we describe a new structural class of neutral tridentate 99mTc(I)-estradiol-pyridin-2-yl hydrazine derivatives for potential use in breast and endometrial cancer imaging. METHODS: The 99mTc(I)-estradiol-pyridin-2-yl hydrazine derivative was synthesized via the Sonogashira cross-coupling reaction and radiolabeled via the tricarbonyl approach. Radiochemical purity was assessed by high-performance liquid chromatography. Cell-binding studies were performed with human breast adenocarcinoma MCF-7 …