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Animals

Kimberly K. Leslie

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Articles 1 - 11 of 11

Full-Text Articles in Medicine and Health Sciences

Acute Intrauterine Infection Results In An Imbalance Between Pro- And Anti-Inflammatory Cytokines In The Pregnant Rabbit., Kimberly Leslie, S. Lee, S. Woodcock, J. Davies, R. Mcduffie, E. Hirsch, M. Sherman, J. Eskens, R. Gibbs Feb 2013

Acute Intrauterine Infection Results In An Imbalance Between Pro- And Anti-Inflammatory Cytokines In The Pregnant Rabbit., Kimberly Leslie, S. Lee, S. Woodcock, J. Davies, R. Mcduffie, E. Hirsch, M. Sherman, J. Eskens, R. Gibbs

Kimberly K. Leslie

PROBLEM: Intrauterine infection results in an increase in cytokines. This study compared the time courses for the pro- and anti-inflammatory cytokine responses in 33 pregnant rabbits at 70% gestation. Pro-inflammatory markers were activated nuclear factor-kappa B (NF-kappaB) in placenta and tumor necrosis factor-alpha (TNF-alpha) in amniotic fluid. These were compared to the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), in placenta and uterus. METHOD OF STUDY: Does were endoscopically inoculated with Escherichia coli through their cervices and sacrificed at six intervals between 0 and 30 hr post-inoculation. RESULTS: Activated NF-kappaB, determined by electromobility gel shift assay, increased significantly 16 hr after …


Histologic Inflammation In The Maternal And Fetal Compartments In A Rabbit Model Of Acute Intra-Amniotic Infection., J. Davies, R. Shikes, C. Sze, Kimberly Leslie, R. Mcduffie, R. Romero, R. Gibbs Feb 2013

Histologic Inflammation In The Maternal And Fetal Compartments In A Rabbit Model Of Acute Intra-Amniotic Infection., J. Davies, R. Shikes, C. Sze, Kimberly Leslie, R. Mcduffie, R. Romero, R. Gibbs

Kimberly K. Leslie

OBJECTIVE: This study was undertaken to determine the course of acute inflammation in the maternal and fetal compartments during experimentally induced ascending intra-amniotic infection. STUDY DESIGN: Forty pregnant rabbits at 70% gestation were inoculated endocervically with 10(5) colony-forming units of Escherichia coli. Does were killed at 0, 4, 8, 16, 24, and 30 hours after inoculation. At necropsy, blood, peritoneal fluid, amniotic fluid, and uterine tissue were cultured. Fetal brain, lung, heart, gut, and kidney were collected for histologic examination. Necrosis, infiltrates, congestion, and edema were each assessed semiquantitatively, and mean composite histologic-inflammation scores were compared with analysis of variance. …


The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie Feb 2013

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.


A Randomized Controlled Trial Of Interleukin-1 Receptor Antagonist In A Rabbit Model Of Ascending Infection In Pregnancy., R. Mcduffie, J. Davies, Kimberly Leslie, S. Lee, M. Sherman, R. Gibbs Feb 2013

A Randomized Controlled Trial Of Interleukin-1 Receptor Antagonist In A Rabbit Model Of Ascending Infection In Pregnancy., R. Mcduffie, J. Davies, Kimberly Leslie, S. Lee, M. Sherman, R. Gibbs

Kimberly K. Leslie

OBJECTIVE: To determine whether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-alpha) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy. METHODS: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 10(6) - 10(7) cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1-2 h after inoculation. Blood was drawn from the does for assay of serum IL1-ra concentration before inoculation, …


Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie Feb 2013

Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie

Kimberly K. Leslie

Endometrial cancer is the most frequent gynecologic cancer in women. Long-term outcomes for patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our study was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin, a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting …


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 Feb 2013

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 …


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 Feb 2013

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 …


Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn Feb 2013

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 Feb 2013

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 …


Oral Contraceptives And Skin Cancer: Is There A Link?, Kimberly Leslie, E. Espey Feb 2013

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 Feb 2013

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 …