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Full-Text Articles in Medicine and Health Sciences
Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange
Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange
Kimberly K. Leslie
No abstract provided.
Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar
Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar
Kimberly K. Leslie
Cancer and its link to reproductive hormones is an area of intense concern for our patients and has been the subject of much speculation. But if estrogen causes breast cancer, for example, most women would eventually develop the disease. We know this is not the case! Actually, estrogen and progesterone have been linked to a decrease as well as an increase in cancer, depending upon the type of tumor under investigation. The purpose of this manuscript is to review the data supporting those relationships.
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium responds to unopposed estrogen stimulation with rapid cell proliferation. Progesterone protects the endometrium against the hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2 terminus and may function differently from hPRA. Thus, the relative expression of hPRA:hPRB is likely to be important for the action of progesterone. We hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial cancer …
Estrogens In Intrahepatic Cholestasis Of Pregnancy., Kimberly Leslie, L. Reznikov, F. Simon, P. Fennessey, H. Reyes, J. Ribalta
Estrogens In Intrahepatic Cholestasis Of Pregnancy., Kimberly Leslie, L. Reznikov, F. Simon, P. Fennessey, H. Reyes, J. Ribalta
Kimberly K. Leslie
OBJECTIVE: To determine whether estrogen production and excretion are impaired in gravidas with intrahepatic cholestasis. METHODS: Plasma and urine samples were collected from 13 women from the United States and Chile at 35-38 weeks' gestation with mild (n = 9) or severe (n = 4) intrahepatic cholestasis of pregnancy. Urinary and plasma steroid levels from women with cholestasis were compared with levels from 27 normal pregnant women within the same gestational age range. Urinary concentrations of dehydroepiandrosterone (DHEA), estrone (E1), estradiol (E2), estriol (E3), estetrol, progesterone, and 16-hydroxy-pregnenolone were measured by gas chromatography mass spectrometry, and plasma concentrations of DHEA …
Oestrogen Modulation With Parturition In The Human Placenta., Kimberly Leslie, D. Zuckerman, J. Schruefer, M. Burchell, J. Smith, B. Albertson
Oestrogen Modulation With Parturition In The Human Placenta., Kimberly Leslie, D. Zuckerman, J. Schruefer, M. Burchell, J. Smith, B. Albertson
Kimberly K. Leslie
An initial group of term (36-41 6/7 weeks), preterm (less than 36 weeks), and post-term (42 or more weeks) placentae were collected from women at delivery to determine the placental levels of important steroids and steroidogenic enzymes involved in the oestrogen synthesis pathway as a function of gestational age. A second group of placentae were obtained from women delivering at term before and after the onset of labour. Placentae were evaluated individually for cytosolic steroid hormone levels and microsomal steroidogenic enzyme activities. Oestradiol (E2), oestrone (E1), progesterone (P), and delta-4-androstenedione (A) were measured by radioimmunoassay in placental cytosols. Aromatase (AR), …
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Kimberly K. Leslie
Recent studies failed to detect estrogen receptors in primate follicles. This study was initiated to determine whether estrogen receptor (ER) messenger ribonucleic acid (mRNA) is present in human granulosa cells and, further, if functional ER proteins are present. To evaluate the presence of ER, RNA from human granulosa cells obtained at the time of oocyte retrieval for assisted reproduction was extracted, and complementary DNA synthesis was performed by the reverse transcriptase-polymerase chain reaction. Oligonucleotide primers were used to amplify basepairs 570-852 in the B- and C- domains of the ER mRNA. Southern blotting was performed and confirmed that the amplified …
Differential Gene Expression In The Amnion, Chorion, And Trophoblast Of The Human Placenta., C. Plouzek, Kimberly Leslie, J. Stephens, J. Chou
Differential Gene Expression In The Amnion, Chorion, And Trophoblast Of The Human Placenta., C. Plouzek, Kimberly Leslie, J. Stephens, J. Chou
Kimberly K. Leslie
Human chorionic gonadotrophin (hCG), placental alkaline phosphatase (PLAP), and pregnancy-specific glycoprotein (PSG) are three major proteins produced by the trophoblast of the human placenta. Immunocytochemical studies suggest that PSG and hCG are also present in the human amnion. In this study, we examined whether amniotic and chorionic membranes were capable of expressing trophoblastic-specific genes. As previously reported, trophoblasts express high levels of hCG beta, hCG alpha, PLAP, and PSG. Both amnion and chorion were found to express PLAP and hCG beta mRNA. However, the hCG alpha transcript was expressed only by the amnion, but not by the chorion in the …
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
Kimberly K. Leslie
Most of our knowledge of ovarian physiology is based upon studies that have demonstrated functional oestrogen receptors in the ovaries of lower animal species. The presence of oestrogen receptors in primate granulosa cells has been questioned by some investigators. However, we have found oestrogen receptor messenger RNA in human granulosa cells by reverse transcriptase-PCR assay. Furthermore, using immortalized granulosa cell lines transfected with a plasmid containing an oestrogen response element, a functional oestrogen receptor was confirmed. These experiments strongly support the hypothesis that human granulosa cells express biologically active oestrogen receptor.
Low Serum Estradiol And High Serum Progesterone Concentrations Characterize Hypertensive Pregnancies At High Altitude., S. Zamudio, Kimberly Leslie, M. White, D. Hagerman, L. Moore
Low Serum Estradiol And High Serum Progesterone Concentrations Characterize Hypertensive Pregnancies At High Altitude., S. Zamudio, Kimberly Leslie, M. White, D. Hagerman, L. Moore
Kimberly K. Leslie
OBJECTIVE: Intrauterine growth retardation and preeclampsia are more common at high than at low altitude. Because altered hormonal profiles have been linked with these disorders, we asked whether placental steroid hormone concentrations were altered during pregnancy at high altitude. METHODS: We measured progesterone, unconjugated estradiol, and estriol (by radioimmunoassay) at weeks 20, 30, and 36 of pregnancy in 18 women at low altitude (1600 m) and 40 women at high altitude (3100 m). RESULTS: Women at 3100 m compared with 1600 m had lower serum estradiol concentrations at week 36 of pregnancy, and lower estriol and higher progesterone concentrations throughout …
Pregnancy Specific Beta 1 Glycoprotein (Sp-1) In Maternal Serum And Amniotic Fluid; Pre-Eclampsia, Small For Gestational Age Fetus And Fetal Distress., R. Silver, K. Heyborne, Kimberly Leslie
Pregnancy Specific Beta 1 Glycoprotein (Sp-1) In Maternal Serum And Amniotic Fluid; Pre-Eclampsia, Small For Gestational Age Fetus And Fetal Distress., R. Silver, K. Heyborne, Kimberly Leslie
Kimberly K. Leslie
Pregnancy specific beta 1 glycoprotein (SP-1) levels have been suggested to correlate with certain obstetrical complications. We compared maternal serum SP-1 levels in normal pregnancies (N = 82), and pregnancies complicated by pre-eclampsia (N = 37), small for gestational age fetuses (N = 8) and fetal distress (N = 13). We also compared levels of this protein in mid-trimester amniotic fluid samples obtained from normal (N = 47) and small for gestational age fetuses (N = 25). Despite trends towards low maternal serum and amniotic fluid SP-1 values in complicated pregnancies, there were no statistically significant differences in their levels …
Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin
Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin
Kimberly K. Leslie
OBJECTIVE: The antiestrogen tamoxifen has been found to be effective in decreasing glioblastoma cell proliferation, but the mechanism underlying this effect and whether it is through the estrogen receptor (ER) is controversial. The objective of this study was to determine whether ERs are present in three human glioblastoma cell lines--HS683, U138MG, and JHN J889H--using the most sensitive techniques available. METHODS: Ligand binding and flow cytometry were employed to identify estrogen and progesterone receptors. The reverse transcriptase-polymerase chain reaction was used to identify ER mRNA, and a novel reporter gene transfection assay demonstrated that the ER was capable of activating gene …
Linkage Of Two Human Pregnancy-Specific Beta 1-Glycoprotein Genes: One Is Associated With Hydatidiform Mole., Kimberly Leslie, S. Watanabe, K. Lei, D. Chou, C. Plouzek, H. Deng, J. Torres, J. Chou
Linkage Of Two Human Pregnancy-Specific Beta 1-Glycoprotein Genes: One Is Associated With Hydatidiform Mole., Kimberly Leslie, S. Watanabe, K. Lei, D. Chou, C. Plouzek, H. Deng, J. Torres, J. Chou
Kimberly K. Leslie
A genomic clone containing two linked human pregnancy-specific beta 1-glycoprotein (PS beta G) genes has been isolated and characterized. The two genes are arranged in the same 5'----3' orientation; the 3' region (including the A2 and B-C exons) of the upstream gene, PSGGA, is linked to the 5' region (including the 5'/L and L/N exons) of PSGGB, the downstream gene. Depending upon the domains compared, PSGGA and PSGGB share 92-98% nucleotide and 86-95% amino acid sequence identity with PSG93, the most abundant PS beta G transcript. The 3' exon (B-C) of PSGGA contains four alternative splice sites and three polyadenylylation …
Molecular Tools To Reestablish Progestin Control Of Endometrial Cancer Cell Proliferation., D. Dai, N. Kumar, D. Wolf, Kimberly Leslie
Molecular Tools To Reestablish Progestin Control Of Endometrial Cancer Cell Proliferation., D. Dai, N. Kumar, D. Wolf, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Endometrial cancers often arise in a setting of estrogen stimulation unopposed by the differentiating effects of progesterone. Our laboratory and others have previously shown that progesterone receptor down-regulation or perturbation of progesterone receptor isoform A or B expression is associated with the development of poorly differentiated endometrial cancers that are not growth inhibited by progestins. The purpose of these studies was to reestablish high progesterone receptor isoform A and B gene expressions in such endometrial cancer cells and to examine the effects of progestin treatment on cell growth and metastatic potential after this transformation. STUDY DESIGN: To induce high …
Functional Analysis Of A Mutant Estrogen Receptor Isolated From T47dco Breast Cancer Cells., Kimberly Leslie, D. Tasset, K. Horwitz
Functional Analysis Of A Mutant Estrogen Receptor Isolated From T47dco Breast Cancer Cells., Kimberly Leslie, D. Tasset, K. Horwitz
Kimberly K. Leslie
OBJECTIVE: Estrogen receptor-positive cancers that initially respond to hormone therapy often progress to a resistant state. The breast cancer cell line T47Dco is a model for such resistance. It is a polymorphic line, composed of multiple cell populations that demonstrate the presence of mutant estrogen receptors by cloning and sequencing techniques. Our objective was to isolate and analyze the structural and functional characteristics of the T47Dco mutant estrogen receptor complementary deoxyribonucleic acid clones. STUDY DESIGN: We constructed two independent T47Dco complementary deoxyribonucleic acid libraries. We isolated and sequenced T47Dco estrogen receptors and have identified a mutant receptor that is truncated …
Immunomodulatory And Transcriptional Effects Of Progesterone Through Progesterone A And B Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells, S. Davies, Donghai Dai, D. Wolf, Kimberly Leslie
Immunomodulatory And Transcriptional Effects Of Progesterone Through Progesterone A And B Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells, S. Davies, Donghai Dai, D. Wolf, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Derivatives of progesterone, progestins, are used to treat endometrial cancer; however, the pathways activated by the hormone have not been fully investigated. Progesterone acts through two receptor isoforms, progesterone receptors A and B (PRA and PRB), transcription factors that control the expression of downstream genes leading to endometrial differentiation. The purpose of this study was to perform an expression analysis to identify the mechanisms underlying progesterone's growth suppressive and immunomodulatory effects in endometrial cancer. METHODS: To study the molecular effects of progesterone, PRs were introduced into Hec50co cells. Expression array analyses followed by confirmatory semiquantitive reverse-transcriptase polymerase chain reaction …
Cadherins, Catenins And Cell Cycle Regulators: Impact On Survival In A Gynecologic Oncology Group Phase Ii Endometrial Cancer Trial, M. Singh, K. Darcy, W. Brady, R. Clubwala, Z. Weber, J. Rittenbach, A. Akalin, C. Whitney, R. Zaino, N. Ramirez, Kimberly Leslie
Cadherins, Catenins And Cell Cycle Regulators: Impact On Survival In A Gynecologic Oncology Group Phase Ii Endometrial Cancer Trial, M. Singh, K. Darcy, W. Brady, R. Clubwala, Z. Weber, J. Rittenbach, A. Akalin, C. Whitney, R. Zaino, N. Ramirez, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: We evaluated the clinical relevance of catenins, cadherins and cell cycle regulators in stage IV or recurrent endometrial carcinoma in a multi-center phase II trial (GOG protocol #119). METHODS: Tissue microarrays of metastatic or recurrent (n=42) tumor were developed and immunohistochemistry was performed. Average expression (percent staining x intensity) was assessed in tumor epithelium ((E)) and stroma ((S)) and categorized into tertiles (T1, T2, T3) for E-cadherin(E), N-cadherin(E), alpha-catenin(E), beta-catenin(E), gamma-catenin(E), p120-catenin(E) and Ki-67(E); as negative, below median or above median for p16(E), p27(E) and CD44(S); or as negative or positive for p53(E), Ki-67(S) and APC(S) (adenomatous polyposis coli). …
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Kimberly K. Leslie
Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …
Identification Of Proteins Within The Nuclear Factor-Kappa B Transcriptional Complex Including Estrogen Receptor-Alpha, I. Feldman, G. Feldman, C. Mobarak, J. Dunkelberg, Kimberly Leslie
Identification Of Proteins Within The Nuclear Factor-Kappa B Transcriptional Complex Including Estrogen Receptor-Alpha, I. Feldman, G. Feldman, C. Mobarak, J. Dunkelberg, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: The objective of the study was to determine whether cross-talk occurs between estrogen receptors (ERs) and nuclear factor-kappa-B (NF-kappaB), to assess the functional consequences of such an ER/NF-kappaB interaction, and to identify other unknown regulatory proteins that may participate in the NF-kappaB transcriptional complex. STUDY DESIGN: Electromobility gel shifts, reporter gene assays, and mass spectrometry were used to identify proteins interacting with the NF-kappaB deoxyribonucleic acid (DNA) response element. RESULTS: ER and the p65 subunit of NF-kappaB colocalized on DNA. This interaction was inhibitory for ER transcriptional activity. Sequencing of proteins bound to the NF-kappaB/DNA complex identified DNA-modifying enzymes, …
A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie
A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations. METHODS: Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. …
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium and cancers derived from it are classic models of hormone action: estrogen promotes growth and progesterone inhibits proliferation and results in differentiation. We have now identified a major pathway through which progesterone causes these growth-limiting effects. Ligand-bound progesterone receptors modulate the composition and transcriptional activity of members of the activating protein-1 (AP-1) family, and in particular, c-Jun. First, a dominant negative form of c-Jun inhibits the constitutive growth of Hec50co cells in a manner similar to the effects of progesterone through progesterone B receptors. Second, progesterone inhibits the transcriptional activity of the AP-1 complex in reporter gene …
Endometrial Cancer: Reviving Progesterone Therapy In The Molecular Age, S. Yang, K. Thiel, Koen De Geest, Kimberly Leslie
Endometrial Cancer: Reviving Progesterone Therapy In The Molecular Age, S. Yang, K. Thiel, Koen De Geest, Kimberly Leslie
Kimberly K. Leslie
Endometrial cancer is the most common gynecologic malignancy and represents a major health concern because overall five-year survival rates have not improved in the last three decades. A great deal of research demonstrates that the endometrium is extremely sensitive to hormones, and a shift in the estrogen:progesterone balance is the major cause for the development of endometrial cancer. Progestin-based therapy has proven effective in a subset of patients, particularly in situations where expression of progesterone receptor (PR) is maintained. However, this approach is not routinely used in the clinic in the U.S. for several reasons. For example, many endometrial tumors …
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
Kimberly K. Leslie
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 …
Effect Of Tamoxifen On Endometrial Histology, Hormone Receptors, And Cervical Cytology: A Prospective Study With Follow-Up, Kimberly Leslie, S. Walter, K. Torkko, J. Stephens, C. Thompson, M. Singh
Effect Of Tamoxifen On Endometrial Histology, Hormone Receptors, And Cervical Cytology: A Prospective Study With Follow-Up, Kimberly Leslie, S. Walter, K. Torkko, J. Stephens, C. Thompson, M. Singh
Kimberly K. Leslie
OBJECTIVES: Our major hypothesis for these studies was that tamoxifen's varied effects on the endometrium might be due in part to differences in effect on estrogen and progesterone receptors [ER, progesterone receptor isoform A (PRA), and progesterone receptor isoform B (PRB)]. We aimed to evaluate the changes in histology in serial endometrial biopsies (Em bx), Papanicolaou smears (Pap smears), and endometrial ultrasounds as well as changes in the expression of ER, PRA, and PRB in response to tamoxifen. We propose that understanding and correlating the dynamics of receptor expression with histologic and cytologic changes will help us better understand the …
Relationship Of Estrogen And Progesterone Receptors To Clinical Outcome In Metastatic Endometrial Carcinoma: A Gynecologic Oncology Group Study, M. Singh, R. Zaino, V. Filiaci, Kimberly Leslie
Relationship Of Estrogen And Progesterone Receptors To Clinical Outcome In Metastatic Endometrial Carcinoma: A Gynecologic Oncology Group Study, M. Singh, R. Zaino, V. Filiaci, Kimberly Leslie
Kimberly K. Leslie
INTRODUCTION: The goal of this study was to explore the relationship between the expression of hormone receptors in metastatic endometrial tumors and clinical response to daily tamoxifen citrate and intermittent weekly medroxyprogesterone acetate. STUDY DESIGN: Patients with measurable recurrent or advanced endometrial cancer were enrolled on a clinical trial, Gynecologic Oncology Group Study 119. A pretreatment tumor biopsy was obtained and subjected to immunohistochemical analyses. Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PR) were assessed on frozen tissues, and PR isoforms A and B were detected on fixed tissues. The receptors were scored using a semi-quantitative HSCORE, with a cut off …
Phase Ii Trial Of Bevacizumab In Recurrent Or Persistent Endometrial Cancer: A Gynecologic Oncology Group Study, C. Aghajanian, M. Sill, K. Darcy, B. Greer, D. Mcmeekin, P. Rose, J. Rotmensch, M. Barnes, P. Hanjani, Kimberly Leslie
Phase Ii Trial Of Bevacizumab In Recurrent Or Persistent Endometrial Cancer: A Gynecologic Oncology Group Study, C. Aghajanian, M. Sill, K. Darcy, B. Greer, D. Mcmeekin, P. Rose, J. Rotmensch, M. Barnes, P. Hanjani, Kimberly Leslie
Kimberly K. Leslie
PURPOSE: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), has clinical activity in multiple tumor types. We conducted a phase II trial to assess the activity and tolerability of single-agent bevacizumab in recurrent or persistent endometrial cancer (EMC). PATIENTS AND METHODS: Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of
Progesterone: The Ultimate Endometrial Tumor Suppressor, S. Yang, K. Thiel, Kimberly Leslie
Progesterone: The Ultimate Endometrial Tumor Suppressor, S. Yang, K. Thiel, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium is exquisitely sensitive to steroid hormones that act through well-described nuclear receptors. Estrogen drives epithelial proliferation, and progesterone inhibits growth and causes cell differentiation. The importance of progesterone as a key inhibitor of carcinogenesis is reflected by the observation that women who ovulate and produce progesterone almost never get endometrial cancer. In this review we describe seminal research findings that define progesterone as the major endometrial tumor suppressor. We discuss the genes and diverse signaling pathways that are controlled by progesterone through progesterone receptors (PRs) and also the multiple factors that regulate progesterone/PR activity. By defining these …
Gene Regulation Profiles By Progesterone And Dexamethasone In Human Endometrial Cancer Ishikawa H Cells, S. Davies, Donghai Dai, G. Pickett, Kimberly Leslie
Gene Regulation Profiles By Progesterone And Dexamethasone In Human Endometrial Cancer Ishikawa H Cells, S. Davies, Donghai Dai, G. Pickett, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Progesterone and glucocorticoids such as dexamethasone mediate distinct biological functions, yet they bind to receptors that recognize the same consensus DNA response element. In breast cancer, progestins are associated with the incidence and progression of tumors, whereas glucocorticoids are growth-suppressive in mammary cancer cells; the differential effects of these two steroids are less well understood in the hormone-dependent disease cancer of the uterine endometrium. We set out to identify genes that are regulated by progesterone through progesterone receptors and dexamethasone through glucocorticoid receptors in a well-differentiated human endometrial cancer cell line. METHODS: PR- and GR-positive Ishikawa H endometrial cancer …
Gpr30: A Novel Indicator Of Poor Survival For Endometrial Carcinoma, H. Smith, Kimberly Leslie, M. Singh, C. Qualls, C. Revankar, N. Joste, E. Prossnitz
Gpr30: A Novel Indicator Of Poor Survival For Endometrial Carcinoma, H. Smith, Kimberly Leslie, M. Singh, C. Qualls, C. Revankar, N. Joste, E. Prossnitz
Kimberly K. Leslie
OBJECTIVE: This study was undertaken to evaluate the relationship between GPR30, classical steroidal receptor expression, and clinical outcome in patients with endometrial carcinoma. STUDY DESIGN: Immunohistochemistry was used to investigate the expression of GPR30, estrogen, progesterone, epidermal growth factor receptors and Ki-67 in 47 consecutive consenting patients with endometrial carcinoma diagnosed between 1997 and 2001. Results were correlated with clinical and pathologic predictors of adverse outcome and survival. RESULTS: GPR30 correlated positively with epidermal growth factor receptor (P = .005), but negatively with progesterone (P = .05) receptor expression. GPR30 overexpression occurred more frequently in tumors with deep myometrial invasion, …
Endometrial Cancer: Potential Treatment And Prevention With Progestin-Containing Intrauterine Devices, Kimberly Leslie, K. Thiel, S. Yang
Endometrial Cancer: Potential Treatment And Prevention With Progestin-Containing Intrauterine Devices, Kimberly Leslie, K. Thiel, S. Yang
Kimberly K. Leslie
No abstract provided.
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
Kimberly K. Leslie
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 …