Medicine and Health Sciences Commons^™

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

Xiangbing Meng

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

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 Laidler, Lina Albitar, Anna Holmes, Donghai Dai, Thomas Buekers, David Bender, Kimberly Leslie

Xiangbing Meng

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.

Toward A Microrna Signature Of Endometrial Cancer, Eric J. Devor, Michael J. Goodheart, Kimberly K. Leslie

Michael J. Goodheart

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 …

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

Michael J. Goodheart

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.

Toward A Microrna Signature Of Endometrial Cancer, Eric J. Devor, Michael J. Goodheart, Kimberly K. Leslie

Eric J Devor

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 …

Mir-888: A Newly Identified Mirna Significantly Over-Expressed In Endometrial Cancers, Adriann M. Hovey, Eric J. Devor, Kimberly K. Leslie

Eric J Devor

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

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

Eric J Devor

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.

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey

Dissertations & Theses (Open Access)

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.

HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.

METHODS: 253 individuals with an …

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

Donghai Dai

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.

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 Laidler, Lina Albitar, Anna Holmes, Donghai Dai, Thomas Buekers, David Bender, Kimberly Leslie

David P Bender

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.

Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie

David P Bender

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 …

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

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

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

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

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 …

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.