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Maywood, IL, United States

Baritaki S.,University of California at Los Angeles | Yeung K.,Health science Campus | Bonavida B.,University of California at Los Angeles
Forum on Immunopathological Diseases and Therapeutics | Year: 2011

Most tumors develop several strategies to resist conventional chemotherapy as well as to escape from the host immunosurveillance mechanisms. These result in tumor persistence and spread, through activation of the epithelial to mesenchymal transition (EMT) program. The molecular bases of tumor resistance to apoptosis and EMT are thought to be due, in part, to the constitutive activation of survival signaling pathways including NF-κB. RKIP is a member of the PEBP family and it has been implicated in the negative regulation of the NF-κB and MAPK survival pathways. RKIP expression has been found significantly diminished in several tumors and almost absent in metastatic tissues, thus suggesting that RKIP may serve as a metastasis suppressor gene product. We have reported that RKIP overexpression reverses the tumor cell resistance to both chemotherapy and immunotherapy, as well as inhibits the mesenchymal cell phenotype (EMT) in metastatic tumor cell lines. In contrast, RKIP silencing by RKIP siRNA-inhibited TRAIL- or drug-induced apoptosis and induced EMT. RKIP overexpression was paralleled with upregulation of the TRAIL and Fas receptors DR5 and Fas, respectively, through inhibition of their transcriptional repressor Yin Yang 1 (YY1). YY1 siRNA resensitized the cells to TRAIL/FasL and drug apoptosis. RKIP transcription is directly repressed by Snail, a transcriptional target of NF-κB that serves as an EMT inducer through repression of E-cadherin. RKIP overexpression reduced Snail expression through NF-κB inhibition, while Snail silencing reversed both tumor resistance and EMT. Novel therapeutics such as the proteasome inhibitor NPI-0052 and the NO donor DETANONOate upregulated RKIP expression and led to tumor cell resensitization to TRAIL and inhibition of EMT. These findings demonstrate that RKIP regulates tumor cell sensitivity to apoptotic stimuli, and inhibits EMT via modulation of the dysregulated NF-κB/YY1/Snail circuitry. We propose that RKIP is a therapeutic target for intervention in the treatment of resistant and metastatic cancers. © 2011 by Begell House, Inc. Source

Grubb B.P.,Electrophysiology Section | Welch M.,Health science Campus | Karabin B.,Electrophysiology Section | Foster W.,Electrophysiology Section | And 2 more authors.
American Journal of Therapeutics | Year: 2012

Infection is a well-recognized complication that can occur after the implantation of cardiac devices such as pacemakers and implantable cardioverter defibrillators (ICDs). Reported infection rates after new device implantation are reported to be around 1%, while infection rates after device generator replacements are higher with a reported average of up to 4-5% per year. Here we report our experience using a modified plastic surgical technique for cardiac device wound closure designed to both reduce infections and enhance cosmetic outcomes. Patients were recruited from among those individuals undergoing routine cardiac device implantation (either new or replacement) at our institution. A total of 124 patients were included in the study. There were 74 women and 48 men, mean age 58 ± 16 years. There were 74 new pacemaker implants and 27 pacemaker generator replacements. There were 17 new ICD generator implants and 6 ICD generator reimplants. Mean follow-up time was 15 ± 16 months. During the follow-up period, there have been no device infections nor any wound dehiscences observed. Each patient felt that the scar was cosmetically acceptable. Two patients developed mild rashes to the clear plastic adhesive that resolved after removal. The modified wound closure technique described above appears to minimize cardiac device wound infections while facilitating cosmetically acceptable wound scar formation. © 2012 Lippincott Williams & Wilkins. Source

Boe D.M.,Health science Campus | Boe D.M.,Loyola University Chicago | Curtis B.J.,Health science Campus | Curtis B.J.,Burn and Shock Trauma Research Institute | And 8 more authors.
Journal of Leukocyte Biology | Year: 2015

MΦ are multipurpose phagocytes with a large repertoire of well-characterized abilities and functions, including regulation of inflammation, wound healing, maintenance of tissue homeostasis, as well as serving as an integral component of the innate-immune defense against microbial pathogens. Working along with neutrophils and dendritic cells, the other myeloid-derived professional phagocytes, MΦ are one of the key effector cells initiating and directing the host reaction to pathogenic organisms and resolving subsequent responses once the threat has been cleared. ETs are a relatively novel strategy of host defense involving expulsion of nuclear material and embedded proteins from immune cells to immobilize and kill bacteria, fungi, and viruses. As research on ETs expands, it has begun to encompass many immune cell types in unexpected ways, including various types of MΦ, which are not only capable of generating METs in response to various stimuli, but recent preclinical data suggest that they are an important agent in clearing ETs and limiting ET-mediated inflammation and tissue damage. This review aims to summarize historical and recent findings of biologic research regarding ET formation and function and discuss the role of MΦ in ET physiology and associated pathologies. © 2015 Federation of American Societies for Experimental Biology. All rights reserved. Source

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