University of Kentucky

About: University of Kentucky is a education organization based out in Lexington, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 43933 authors who have published 92195 publications receiving 3256087 citations. The organization is also known as: UK.

Tamoxifen Resistance in Breast Tumors Is Driven by Growth Factor Receptor Signaling with Repression of Classic Estrogen Receptor Genomic Function

Abstract: Not all breast cancers respond to tamoxifen, and many develop resistance despite initial benefit. We used an in vivo model of estrogen receptor (ER)-positive breast cancer (MCF-7 xenografts) to investigate mechanisms of this resistance and develop strategies to circumvent it. Epidermal growth factor receptor (EGFR) and HER2, which were barely detected in control estrogen-treated tumors, increased slightly with tamoxifen and were markedly increased when tumors became resistant. Gefitinib, which inhibits EGFR/HER2, improved the antitumor effect of tamoxifen and delayed acquired resistance, but had no effect on estrogen-stimulated growth. Phosphorylated levels of p42/44 and p38 mitogen-activated protein kinases (both downstream of EGFR/HER2) were increased in the tamoxifen-resistant tumors and were suppressed by gefitinib. There was no apparent increase in phosphorylated AKT (also downstream of EGFR/HER2) in resistant tumors, but it was nonetheless suppressed by gefitinib. Phosphorylated insulin-like growth factor-IR (IGF-IR), which can interact with both EGFR and membrane ER, was elevated in the tamoxifen-resistant tumors compared with the sensitive group. However, ER-regulated gene products, including total IGF-IR itself and progesterone receptor, remained suppressed even at the time of acquired resistance. Tamoxifen's antagonism of classic ER genomic function was retained in these resistant tumors and even in tumors that overexpress HER2 (MCF-7 HER2/18) and are de novo tamoxifen-resistant. In conclusion, EGFR/HER2 may mediate tamoxifen resistance in ER-positive breast cancer despite continued suppression of ER genomic function by tamoxifen. IGF-IR expression remains dependent on ER but is activated in the tamoxifen-resistant tumors. This study provides a rationale to combine HER inhibitors with tamoxifen in clinical studies, even in tumors that do not initially overexpress EGFR/HER2.

A Survey of Petri Net Methods for Controlled Discrete EventSystems

Abstract: This paper surveys recent research on the application of Petri net models to the analysis and synthesis of controllers for discrete event systems. Petri nets have been used extensively in applications such as automated manufacturing, and there exists a large body of tools for qualitative and quantitative analysis of Petri nets. The goal of Petri net research in discrete event systems is to exploit the structural properties of Petri net models in computationally efficient algorithms for computing controls. We present an overview of the various models and problems formulated in the literature focusing on two particular models, the controlled Petri nets and the labeled nets. We describe two basic approaches for controller synthesis, based on state feedback and event feedback. We also discuss two efficient techniques for the on-line computation of the control law, namely the linear integer programming approach which takes advantage of the linear structure of the Petri net state transition equation, and path-based algorithms which take advantage of the graphical structure of Petri net models. Extensions to timed models are briefly described. The paper concludes with a discussion of directions for future research.

Nanoscale live-cell imaging using hopping probe ion conductance microscopy.

Abstract: We describe hopping mode scanning ion conductance microscopy that allows noncontact imaging of the complex three-dimensional surfaces of live cells with resolution better than 20 nm. We tested the effectiveness of this technique by imaging networks of cultured rat hippocampal neurons and mechanosensory stereocilia of mouse cochlear hair cells. The technique allowed examination of nanoscale phenomena on the surface of live cells under physiological conditions.

Can Illegal Corporate Behavior be Predicted? An Event History Analysis

Abstract: A model of illegal corporate behavior was developed and tested for a 19-year period using event history analysis and data on clearly illegal acts. Results indicated that large firms operating in dy...

Posttraumatic stress disorder after treatment for breast cancer : Prevalence of diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening instrument

Abstract: The presence of a posttraumatic stress disorder (PTSD) diagnosis in women (n = 82) diagnosed with Stage 0-IIIA breast cancer was assessed 6 to 72 months after cancer therapy. The PTSD Checklist-Civilian Version (PCL-C) and the PTSD module for the Structured Clinical Interview for DSM-IV, Nonpatient Version, PTSD module (SCID-NP-PTSD) were administered in a telephone interview. SCID-NP-PTSD results indicated prevalence rates of 6% and 4% for current and lifetime PTSD, respectively. Use of the recommended cutoff score of 50 on the PCL-C to determine diagnosis of current cancer-related PTSD resulted in a sensitivity of .60 and a specificity of .99 with 2 false-negative diagnoses. In conclusion, PTSD can be precipitated by diagnosis and treatment of breast cancer, and the PCL-C can be a cost-effective screening tool for this disorder.