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Full-Text Articles in Medicine and Health Sciences

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 Feb 2013

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 Feb 2013

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 Feb 2013

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 Feb 2013

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 Feb 2013

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.