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- Endometrial cancer (6)
- Endometrium (3)
- MicroRNA (2)
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- BEZ235 (1)
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- Gefitinib (1)
- Genetic intra-tumor heterogeneity (1)
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- Mammalian target of rapamycin (1)
- Metadherin (1)
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- Mitotic catastrophe (1)
- P38 (1)
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- Paclitaxel (1)
- Progesterone (1)
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Articles 1 - 9 of 9
Full-Text Articles in Medicine and Health Sciences
Blocking Epidermal Growth Factor Receptor Signaling In Htr-8/Svneo First Trimester Trophoblast Cells Results In Dephosphorylation Of Pkbα/Akt And Induces Apoptosis, J. Bolnick, L. Albitar, L. L. Laidler, R. Abdullah, Kimberly K. Leslie
Blocking Epidermal Growth Factor Receptor Signaling In Htr-8/Svneo First Trimester Trophoblast Cells Results In Dephosphorylation Of Pkbα/Akt And Induces Apoptosis, J. Bolnick, L. Albitar, L. L. Laidler, R. Abdullah, Kimberly K. Leslie
Kimberly K. Leslie
We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks) that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR) treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to …
Toward A Microrna Signature Of Endometrial Cancer, Eric J. Devor, Michael J. Goodheart, Kimberly K. Leslie
Toward A Microrna Signature Of Endometrial Cancer, Eric J. Devor, Michael J. Goodheart, Kimberly K. Leslie
Kimberly K. Leslie
A simple meta-analysis of eight microRNA (miRNA) expression surveys of endometrial cancers reveals a panel of sixteen miRNAs that are significantly over-expressed (n = 15) or under-expressed (n = 1) in at least three surveys. Examination of these miRNAs indicates that they target mRNAs involved in a number of basic cellular processes including the crucial epithelial to mesenchymal transition (EMT) and hypoxia response. The central role played by these miRNAs is reinforced by the demonstration that they are all among the most ancient of all animal miRNAs. This suggests that they are members of a core set of miRNAs dysregulated …
Combination Therapy With Mtor And Pi3 Kinase Inhibitors Is Broadly Synergistic In A Wide Variety Of Endometrial Cancer Cells, Shujie Yang, Xue Xiao, Xiangbing Meng, Kimberly K. Leslie
Combination Therapy With Mtor And Pi3 Kinase Inhibitors Is Broadly Synergistic In A Wide Variety Of Endometrial Cancer Cells, Shujie Yang, Xue Xiao, Xiangbing Meng, Kimberly K. Leslie
Kimberly K. Leslie
Dysregulation of mammalian target of rapamycin (mTOR) signaling has been found in many human tumors, including endometrial cancer, and mTOR inhibitors have been utilized in clinical trials as targeted therapies with only limited success. Herein we identify a viable treatment alternative that overcomes temsirolimus-induced AKT phosphorylation in endometrial cancer. Our data suggest temsirolimus and BEZ235 inhibit different components of the AKT/mTOR signaling pathway to accomplish synergistic pathway inhibition, which is necessary for therapeutic efficacy to abrogate the increased signaling through AKT that occurs with mTOR inhibition alone
Mir-888: A Newly Identified Mirna Significantly Over-Expressed In Endometrial Cancers, Adriann M. Hovey, Eric J. Devor, Kimberly K. Leslie
Mir-888: A Newly Identified Mirna Significantly Over-Expressed In Endometrial Cancers, Adriann M. Hovey, Eric J. Devor, Kimberly K. Leslie
Kimberly K. Leslie
Endometrial cancer is the most common gynecological malignancy and the fourth most common cancer in women. With accumulating evidence, microRNAs have emerged as significant players in the development and progression of cancers. The data points to miR-888 playing an important functional role in the development of aggressive endometrial tumors. Future research will focus on identifying and validating the targets of miR-888 to elucidate its mechanism of action and support this hypothesis
Defining Genetic Intra-Tumor Heterogeneity: A Chronological Annotation Of Mutational Pathways, Wentao Luo, Fan Wu, Susan R. Atlas, Gavin Pickett, Kimberly K. Leslie, Donghai Dai
Defining Genetic Intra-Tumor Heterogeneity: A Chronological Annotation Of Mutational Pathways, Wentao Luo, Fan Wu, Susan R. Atlas, Gavin Pickett, Kimberly K. Leslie, Donghai Dai
Kimberly K. Leslie
Tumor heterogeneity is believed to be important in tumor progression and its response to therapies. However, despite numerous mutations being reported in human tumors, genetic intra-tumor heterogeneity remains poorly defined. We have developed a novel strategy to provide a chronological annotation of mutational events in a tumor. We used an endometrial tumor from a patient and transplanted it into athymic mice to create many tumor xenografts. While the patient tumor xenografts were initially responsive to raloxifene treatment, xenografts created with cancer cell clones isolated from the same patient tumor showed dramatic differences in response to raloxifene, indicating existence of intra-tumor …
H19/Mir-675 Non-Coding Rna Expression Differentiates Among Cancers Of The Human Endometrium., Eric J. Devor, Jill N. Demik, Brandon M. Schickling, Michael J. Goodheart, Kimberly K. Leslie
H19/Mir-675 Non-Coding Rna Expression Differentiates Among Cancers Of The Human Endometrium., Eric J. Devor, Jill N. Demik, Brandon M. Schickling, Michael J. Goodheart, Kimberly K. Leslie
Kimberly K. Leslie
H19 is a maternally expressed non-coding RNA located at chromosome 11p15.5 near the reciprocally imprinted insulin-like growth factor 2 (IGF2) gene. Though the function of H19 is unknown, it is transcribed during embryonic development after which transcription is absent in all but a few tissues including cardiac muscle, breast, ovary, uterus, and placenta. Linking H19, miR-675 and RB1 expression with serous tumors of the endometrium suggests that RB1 suppression may be a differentiating event in serous tumorigenesis.
Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie
Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium is exquisitely sensitive to hormones, in particular estrogen and progesterone and to a lesser extent androgens and glucocorticoids. These hormones tightly regulate the complex functioning of the female reproductive tract and are intimately involved in controlling the growth, development, and remodeling of reproductive tissues as well as the cyclic changes that occur during the menstrual cycle. Steroids function by binding to nuclear receptor proteins that act as transcription factors to modulate the expression of genes, though many non-genomic effects for steroids have also been described. An imbalance of the hormones leads to cancer. In particular, endometrial carcinogenesis …
Knockdown Of Mtdh Increases Drug Sensitivity To Hdac Inhibitor And Trail Combination Treatment In Endometrial Cancer Cells, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Kimberly K. Leslie
Knockdown Of Mtdh Increases Drug Sensitivity To Hdac Inhibitor And Trail Combination Treatment In Endometrial Cancer Cells, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Kimberly K. Leslie
Kimberly K. Leslie
Understanding the molecular mechanisms of chemoresistance is vital to design therapies to restore chemosensitivity. MTDH mediates drug resistance by regulating expression of genes required for the control of apoptosis and cell cycle. These findings indicate that sensitivity to chemotherapy agents and combination treatment with HDAC inhibitor and TRAIL can be restored by manipulating MTDH, and hence depletion of MTDH is a potentially novel avenue for effective cancer therapy.
The Combination Of Paclitaxel And Gefitinib Inhibits Endometrial Cancer Cells By Inducing Mitotic Catastrophe: Proof Of Principle For Dual Therapy In Endometrial Cancer, Xiangbing Meng, Laura L. Laidler, Lina Albitar, Anna M. Holmes, Donghai Dai, Thomas E. Buekers, David P. Bender, Kimberly K. Leslie
The Combination Of Paclitaxel And Gefitinib Inhibits Endometrial Cancer Cells By Inducing Mitotic Catastrophe: Proof Of Principle For Dual Therapy In Endometrial Cancer, Xiangbing Meng, Laura L. Laidler, Lina Albitar, Anna M. Holmes, Donghai Dai, Thomas E. Buekers, David P. Bender, Kimberly K. Leslie
Kimberly K. Leslie
Serous uterine endometrial cancer is a lethal disease for which new therapeutic regimens are urgently needed. Combinations of chemotherapeutic agents and small molecule growth factor inhibitors have demonstrated activity in cancers from other sites. Our objective was to determine whether such a combination using Paclitaxel and Gefitinib could be active in serous endometrial cancer cells.