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Articles 901 - 923 of 923
Full-Text Articles in Medicine and Health Sciences
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 …
Targeted Treatment Using Monoclonal Antibodies And Tyrosine-Kinase Inhibitors In Pregnancy, A. Robinson, W. Watson, Kimberly Leslie
Targeted Treatment Using Monoclonal Antibodies And Tyrosine-Kinase Inhibitors In Pregnancy, A. Robinson, W. Watson, Kimberly Leslie
Kimberly K. Leslie
An expanding knowledge of the signalling pathways involved in the cell cycle has led to great improvements in the understanding of the molecular events involved in carcinogenesis. The past decade has seen substantial advances with the introduction of several classes of targeted therapeutics for the treatment of various cancers and autoimmune disorders. However, the question arises as to whether pregnant women can take advantage of these new treatments in view of the potential risks to the fetus. Published work suggests that biological agents, like traditional treatments, have the potential to affect the fetus, and should, therefore, be used with caution …
Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn
Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn
Kimberly K. Leslie
OBJECTIVE: Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and cancer growth in vivo. METHODS AND RESULTS: hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma …
Chronic Intrauterine Infection And Inflammation In The Preterm Rabbit, Despite Antibiotic Therapy, R. Gibbs, J. Davies, R. Mcduffie, Kimberly Leslie, M. Sherman, C. Centretto, D. Wolf
Chronic Intrauterine Infection And Inflammation In The Preterm Rabbit, Despite Antibiotic Therapy, R. Gibbs, J. Davies, R. Mcduffie, Kimberly Leslie, M. Sherman, C. Centretto, D. Wolf
Kimberly K. Leslie
OBJECTIVE: In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days. STUDY DESIGN: New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn. At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam. Primary outcomes were positive cultures and histologic inflammation score. Tumor necrosis factor-alpha levels in …
Egfr Isoforms And Gene Regulation In Human Endometrial Cancer Cells, L. Albitar, G. Pickett, M. Morgan, J. Wilken, N. Maihle, Kimberly Leslie
Egfr Isoforms And Gene Regulation In Human Endometrial Cancer Cells, L. Albitar, G. Pickett, M. Morgan, J. Wilken, N. Maihle, Kimberly Leslie
Kimberly K. Leslie
BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation. RESULTS: We investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. …
Lapatinib And Potential Prognostic Value Of Egfr Mutations In A Gynecologic Oncology Group Phase Ii Trial Of Persistent Or Recurrent Endometrial Cancer, Kimberly Leslie, M. Sill, H. Lankes, E. Fischer, A. Godwin, H. Gray, R. Schilder, J. Walker, K. Tewari, P. Hanjani, O. Abulafia, P. Rose
Lapatinib And Potential Prognostic Value Of Egfr Mutations In A Gynecologic Oncology Group Phase Ii Trial Of Persistent Or Recurrent Endometrial Cancer, Kimberly Leslie, M. Sill, H. Lankes, E. Fischer, A. Godwin, H. Gray, R. Schilder, J. Walker, K. Tewari, P. Hanjani, O. Abulafia, P. Rose
Kimberly K. Leslie
OBJECTIVE: A phase II trial was performed to evaluate the efficacy and safety of the tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2, lapatinib, and to explore EGFR, HER2 (EGFR2), phosphorylated ERK MAP kinase (pERK), and Ki67 expression, as well as EGFR mutations in persistent/recurrent endometrial cancer (EC). METHODS: Women with histologically-confirmed, measurable, persistent/recurrent EC following one or two prior regimens were eligible and treated with 1500 mg oral lapatinib daily until progression or severe toxicity. A 2-stage group sequential design was used to evaluate the regimen with 6 month PFS as the primary endpoint. The trial …
Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie
Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie
Kimberly K. Leslie
Progesterone is a critical steroid hormone that controls cell proliferation and differentiation in the female reproductive tract. Progesterone acts through two nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB, respectively), each with unique cellular effects. Loss of PRB has recently been linked to the development of poorly differentiated endometrial tumors, a lethal form of cancer. To study the molecular effects of progesterone, progesterone receptors were introduced into Hec50co endometrial cancer cells by adenoviral vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent kinase inhibitors p21 and p27, thereby significantly reducing the percentage of proliferating cells. Cancer …
Obstetric Forceps Training Using Visual Feedback And The Isometric Strength Testing Unit, Kimberly Leslie, P. Dipasquale-Lehnerz, M. Smith
Obstetric Forceps Training Using Visual Feedback And The Isometric Strength Testing Unit, Kimberly Leslie, P. Dipasquale-Lehnerz, M. Smith
Kimberly K. Leslie
OBJECTIVE: This is a descriptive study that tested the maximum traction residents could apply to forceps during simulations. Visual feedback was then used to reinforce an optimal range of traction, and the ability of residents to reproduce this pull when blinded was assessed. METHODS: Fifty-five residents participated in 6 pulling exercises using an isometric strength testing unit with a real-time computer printout of the force applied. Maximum traction was determined for male and female residents in standing and sitting positions. Visual feedback was then used to estimate whether residents could be trained to reproduce an optimal force range of 30-45 …
Models Representing Type I And Type Ii Human Endometrial Cancers: Ishikawa H And Hec50co Cells, L. Albitar, G. Pickett, M. Morgan, S. Davies, Kimberly Leslie
Models Representing Type I And Type Ii Human Endometrial Cancers: Ishikawa H And Hec50co Cells, L. Albitar, G. Pickett, M. Morgan, S. Davies, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Endometrial cancer models are critical to the advancement of investigation, and Ishikawa H and Hec50co cells have been used as research tools. The purpose of these studies is to verify the degree to which these commonly used cell models share the molecular characteristics of the two major in vivo endometrial cancer subtypes, I and II. METHODS: The studies reported include an analysis of pathologic features, tumor suppressor mutations, detailed karyotyping, and cell cycle regulation. RESULTS: Ishikawa H cells are hormone responsive and have lost PTEN expression. In addition they have lost RB1 expression due to a deletion in exon …
Knockdown Of Mtdh Sensitizes Endometrial Cancer Cells To Cell Death Induction By Death Receptor Ligand Trail And Hdac Inhibitor Lbh589 Co-Treatment, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Khristina Thiel, Kimberly Leslie
Knockdown Of Mtdh Sensitizes Endometrial Cancer Cells To Cell Death Induction By Death Receptor Ligand Trail And Hdac Inhibitor Lbh589 Co-Treatment, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Khristina Thiel, Kimberly Leslie
Kimberly K. Leslie
Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH correlates with poor clinical outcome in breast cancer, neuroblastoma, hepatocellular carcinoma and prostate cancer. MTDH is also highly expressed in advanced endometrial cancers, a disease for which new therapies are urgently needed. In this present study, we focused on the therapeutic benefit of MTDH depletion in endometrial cancer cells to restore sensitivity to cell death. Cells were treated with a combination of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which …
Oral Contraceptives And Skin Cancer: Is There A Link?, Kimberly Leslie, E. Espey
Oral Contraceptives And Skin Cancer: Is There A Link?, Kimberly Leslie, E. Espey
Kimberly K. Leslie
The skin expresses estrogen, progesterone, and androgen receptors. In the presence of steroid hormones, such as those contained in oral contraceptives, the skin likely responds to hormonal signals that control the cell cycle, apoptosis, DNA replication, and other cellular functions. Some estrogen-responsive pathways have the potential to promote tumor development, including the augmentation of epidermal growth factor signaling, the expression of proto-oncogenes, and inhibition of apoptosis. The question of whether oral contraceptives increase the risk for the development of skin cancer, particularly melanoma, is still an area of concern. This paper reviews the available evidence, the bulk of which suggests …
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
Kimberly K. Leslie
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 …
An Exploratory Study Of The Variables Impacting Preterm Birth Rates In New Mexico, K. Gwin, R. Schrader, K. Peters, A. Moreno, K. Thiel, Kimberly Leslie
An Exploratory Study Of The Variables Impacting Preterm Birth Rates In New Mexico, K. Gwin, R. Schrader, K. Peters, A. Moreno, K. Thiel, Kimberly Leslie
Kimberly K. Leslie
BACKGROUND: Preterm birth (PTB) is a substantial health problem that accounts for significant infant morbidity and mortality and poses an economic burden to both individuals and the state of residence. The goal of this study was to identify maternal risk factors for PTB in New Mexico, a poor state with a unique ethnic background, in order to identify populations at increased risk that would benefit from intervention. METHODS: This was a cross-sectional retrospective exploratory analysis of 377,770 singleton live births in the state of New Mexico from 1991-2005. Gestational age of less than 37 weeks was defined as PTB. The …
Breast Cancer And Pregnancy, Kimberly Leslie, C. Lange
Breast Cancer And Pregnancy, Kimberly Leslie, C. Lange
Kimberly K. Leslie
This article addresses a challenging diagnostic and treatment dilemma encountered in the care of pregnant women-breast cancer. The treatment of a breast cancer is significantly affected by an ongoing pregnancy and may result in an increased risk for a poor outcome in the mother. The definition, incidence, mechanism, diagnosis, and treatment of breast cancer associated with pregnancy and the normal physiologic and endocrine changes in the breast during pregnancy that contribute to the difficulty encountered by practitioners in diagnosing and treating the disorder are reviewed. The risks associated with pregnancy after breast cancer treatment and the effect of pregnancy on …
Chemotherapeutic Drugs In Pregnancy, Kimberly Leslie, C. Koil, W. Rayburn
Chemotherapeutic Drugs In Pregnancy, Kimberly Leslie, C. Koil, W. Rayburn
Kimberly K. Leslie
Chemotherapy may be indicated for the treatment of cancer during pregnancy. The decision to use chemotherapy significantly impacts the pregnancy, and in turn the pregnancy may affect the treatment options available to patients with cancer. This review provides information about the effects of chemotherapeutic agents in pregnancy, taking into account both the mother and the fetus. For convenience, the agents are divided into categories based upon class and mechanism of action. These include alkylating agents, antimetabolites, nucleoside analogs, topoisomerase I inhibitors, topisomerase II inhibitors, vinca alkaloids, taxanes, and biologics such as signaling and growth factor blocking agents.
An Inhibitor Of K+ Channels Modulates Human Endometrial Tumor-Initiating Cells, B. Schickling, N. Aykin-Burns, Kimberly Leslie, D. Spitz, V. Korovkina
An Inhibitor Of K+ Channels Modulates Human Endometrial Tumor-Initiating Cells, B. Schickling, N. Aykin-Burns, Kimberly Leslie, D. Spitz, V. Korovkina
Kimberly K. Leslie
BACKGROUND: Many potassium ion (K+) channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC), are critical to cancer progression. RESULTS: A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA), was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was …
Chronic Hepatitis C In Pregnancy, E. Berkley, Kimberly Leslie, S. Arora, C. Qualls, J. Dunkelberg
Chronic Hepatitis C In Pregnancy, E. Berkley, Kimberly Leslie, S. Arora, C. Qualls, J. Dunkelberg
Kimberly K. Leslie
OBJECTIVE: To estimate outcomes, to determine whether appropriate follow-up was performed for pregnant patients with hepatitis C virus (HCV), and to show that maternal and neonatal complications would be higher in the HCV-positive group. METHODS: We compared pregnant women from a drug dependence and treatment program who were HCV antibody-positive with those who were HCV antibody-negative using the University of New Mexico Perinatal Database. Maternal and neonatal outcomes were evaluated, including cholestasis of pregnancy, preterm birth, low birth weight, neonatal intensive care unit admissions, and neonatal methadone withdrawal. Variables were compared using Student t, Fisher exact, and chi(2) tests. RESULTS: …
Consequences Of The Loss Of P53, Rb1, And Pten: Relationship To Gefitinib Resistance In Endometrial Cancer, L. Albitar, M. Carter, S. Davies, Kimberly Leslie
Consequences Of The Loss Of P53, Rb1, And Pten: Relationship To Gefitinib Resistance In Endometrial Cancer, L. Albitar, M. Carter, S. Davies, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: These studies demonstrate how loss of function mutations or downregulation of key tumor suppressors missing from type I and type II endometrial cancer cells contributes to carcinogenesis and to resistance to the EGFR inhibitor gefitinib (ZD1839). METHODS: Cell models devoid of tumor suppressors PTEN and RB1 or PTEN were studied. PTEN, RB1 and p53 expression was reinstated, and the effects on cell cycle, apoptosis, and cell cycle regulators were evaluated. RESULTS: In Ishikawa H cells that model type I endometrial cancer in the loss of PTEN and RB1, re-expressing PTEN and RB1 increased the apoptotic and G1 phases and …
Knowledge Of Breast Disease And Breast Pathology In The Obstetrics And Gynecology Resident, Andra K. Cicero
Knowledge Of Breast Disease And Breast Pathology In The Obstetrics And Gynecology Resident, Andra K. Cicero
Andra Cicero, DO, FACOG
No abstract provided.