Medicine and Health Sciences Commons^™

Double-Stranded Rna-Dependent Protein Kinase Regulates The Motility Of Breast Cancer Cells, Mei Xu, Gang Chen, Siying Wang, Mingjun Liao, Jacqueline A. Frank, Kimberly A. Bower, Zhuo Zhang, Xianglin Shi, Jia Luo

Internal Medicine Faculty Publications

Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is an interferon-induced protein kinase that plays a central role in the anti-viral process. Due to its pro-apoptotic and anti-proliferative action, there is an increased interest in PKR modulation as an anti-tumor strategy. PKR is overexpressed in breast cancer cells; however, the role of PKR in breast cancer cells is unclear. The expression/activity of PKR appears inversely related to the aggressiveness of breast cancer cells. The current study investigated the role of PKR in the motility/migration of breast cancer cells. The activation of PKR by a synthesized dsRNA (PIC) significantly decreased the motility of …

A Phase Ii Study Of Pulse Dose Imatinib Mesylate And Weekly Paclitaxel In Patients Aged 70 And Over With Advanced Non-Small Cell Lung Cancer, Julie E. Bauman, Keith D. Eaton, Sarah G. Wallace, Laurie L. Carr, Sang-Joon Lee, Dennie V. Jones, Hugo Arias-Pulido, Lisa A. Cerilli, Renato G. Martins

Internal Medicine Faculty Publications

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR).

METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Coronary Artery Remodeling In A Model Of Left Ventricular Pressure Overload Is Influenced By Platelets And Inflammatory Cells, Fanmuyi Yang, Anping Dong, Paul Mueller, Jessica Caicedo, Alyssa Moore Sutton, Juliana Odetunde, Cordelia J. Barrick, Yuri M. Klyachkin, Ahmed Abdel-Latif, Susan S. Smyth

Internal Medicine Faculty Publications

Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, …

Scavenger Receptor Cd36 Expression Contributes To Adipose Tissue Inflammation And Cell Death In Diet-Induced Obesity, Lei Cai, Zhen Wang, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.

EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.

RESULTS: Compared to WT …

Insulin Degludec, The New Generation Basal Insulin Or Just Another Basal Insulin?, Sami N. Nasrallah, L. Raymond Reynolds

Internal Medicine Faculty Publications

The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated. Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Davis Gates, Heribert Staudinger

Internal Medicine Faculty Publications

Background:

The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods:

Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged =40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% …

Effects Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination Formulation On Chronic Obstructive Pulmonary Disease (Copd): Results From A 52-Week Phase Iii Trial In Subjects With Moderate-To-Very Severe Copd, Dennis E. Doherty, Donald P. Tashkin, Edward Kerwin, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

RATIONALE: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).

METHODS: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The trial's co-primary endpoints were mean changes from baseline, as area under the curve (AUC), …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

Background: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.

Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 …

Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers

Internal Medicine Faculty Publications

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients.

METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. …

Intracranial Pressure Is A Better Predictor Of Mortalitythan Cerebral Perfusion Pressure, Ronald J. Markert, Jonathan M. Saxe, Cathryn L. Chadwick

Internal Medicine Faculty Publications

Objective: To evaluate whether elevated intracranial pressure (ICP) or depressed cerebral perfusion pressure (CPP) is a better predictor of intracranial compartment syndrome and long-term functional outcomes in blunt traumatic brain injury.

Methods: This was a retrospective evaluation of data collected on 203 patients with blunt traumatic brain injury who were admitted to Miami Valley Hospital, a Level I trauma center, over a 2 years period, whose initial hospital management required an intracranial pressure monitor. Serial measurements of ICP and CPP were recorded during the patients’ hospital stay. These patients were then evaluated at 3,6,12 and 24 months post-injury to assess …