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Yi M.,Proteogenomics Research Institute for Systems Medicine
PLoS ONE | Year: 2012

Annexin A1 is a multi functional molecule which is involved in inflammation, innate and adaptive immune systems, tumor progression and metastasis. We have previously showed the impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1 knockout mice. While tumor is a piece of heterogeneous mass including not only malignant tumor cells but also the stroma, the importance of the tumor stroma for tumor progression and metastasis is becoming increasingly clear. The tumor stroma is comprised by various components including extracellular matrix and non-malignant cells in the tumor, such as endothelial cells, fibroblasts, immune cells, inflammatory cells. Based on our previous finding of pro-angiogenic functions for annexin A1 in vascular endothelial cell sprouting, wound healing, tumor growth and metastasis, and the previously known properties for annexin A1 in immune cells and inflammation, this study hypothesized that annexin A1 is a key functional player in tumor development, linking the various components in tumor stroma by its actions in endothelial cells and immune cells. Using systems analysis programs commercially available, this paper further compared the gene expression between tumors from annexin A1 wild type mice and annexin A1 knockout mice and found a list of genes that significantly changed in the tumor stroma that lacked annexin A1. This revealed annexin A1 to be an effective regulator in tumor stroma and suggested a mechanism that annexin A1 affects tumor development and metastasis through interaction with the various components in the microenvironment surrounding the tumor cells. © 2012 Ming Yi. Source

Schnitzer J.E.,Proteogenomics Research Institute for Systems Medicine
Recent Results in Cancer Research | Year: 2010

All blood vessels are lined by a layer of endothelial cells that help to control vascular permeability. The luminal surface of vascular endothelial cells is studded with transport vesicles called caveolae that are directly in contact with the blood and can transport molecules into and across the endothelium. The vasculature within distinct tissue types expresses a unique array of proteins that can be used to target intravenously injected antibodies directly to that tissue. When the tissuespecific proteins are concentrated in caveolae, the antibodies can be rapidly pumped out of the blood and into the tissue. Tumors appear to be a distinct tissue type with their own unique marker proteins. Targeting accessible proteins at the surface of tumor vasculature with radiolabeled antibodies destroys tumors and drastically increases animal survival. One day, it may be possible to specifically pump targeted molecules into tumors. This could increase therapeutic efficacy and decrease side effects because most of the drug would accumulate specifically in the tumor. Thus, targeting caveolae may provide a universal portal to pump drugs, imaging agents, and gene vectors out of the blood and into underlying tissue. © 2010 Springer-Verlag Berlin Heidelberg. Source

Chrastina A.,Proteogenomics Research Institute for Systems Medicine | Schnitzer J.E.,Proteogenomics Research Institute for Systems Medicine
Experimental Lung Research | Year: 2012

Pulmonary infarction is a life-threatening lung injury that requires rapid and accurate diagnosis for proper treatment. Targetable and reproducible small-animal models that would allow experimental development and preclinical evaluation of diagnostic methods for detecting pulmonary infarction are critically missing. The authors report here a novel procedure to selectively induce pulmonary infarction by photodestructive laser-light irradiation in a targeted location within a specific lung compartment after administration of a photosensitizer. Histopathological analysis of the illuminated lung tissue revealed massive hemorrhage and vascular occlusion after acute injury localized to the site of irradiation. Collapse of alveolar structure, neutrophil influx, and necrosis were subsequently observed. Computed tomography (CT) scans showed evidence of abnormal density and airspace consolidation in the irradiated area of the lung, but not elsewhere in the lung compartment. Perfusion imaging using 99mTc-labeled macroaggregated albumin by single-photon emission computed tomography revealed diminished scintigraphic signal in the opaque area of infarcted lung tissue. The histological changes, CT findings, and perfusion characteristics of pulmonary infarction are mimicked using laser-irradiated, photosensitizer-mediated photodestruction to selectively induce chronic lung injury in a localized area. This small-animal model can be easily and readily used for targeted induction of pulmonary infarction in a designated area of lung compartment and offers the potential for use in evaluating novel diagnostic and therapeutic methods. © 2011 Informa Healthcare USA, Inc. Source

Chrastina A.,Proteogenomics Research Institute for Systems Medicine | Pokreisz P.,Catholic University of Leuven | Schnitzer J.E.,Proteogenomics Research Institute for Systems Medicine
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2014

We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically irradiated was triangulated from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration, and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury, was significantly elevated at 6 h (41 ± 6 ng/ml, n 4, P<0.05 vs. baseline) and returned to baseline after 72 h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25 ± 3% of the left ventricle at day 1 with a decrease to 20 ± 3% at day 40 (n 6 for each group, P <0.01 vs. day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatiotemporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n 51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions. © 2014 the American Physiological Society. Source

Lopez E.,Research Center i 12 | Madero L.,Hospital Infantil Universitario Nino Jesus | Lopez-Pascual J.,Hospital Universitario 12 Of Octubre | Latterich M.,Proteogenomics Research Institute for Systems Medicine
Proteome Science | Year: 2012

Since the advent of the new proteomics era more than a decade ago, large-scale studies of protein profiling have been used to identify distinctive molecular signatures in a wide array of biological systems, spanning areas of basic biological research, clinical diagnostics, and biomarker discovery directed toward therapeutic applications. Recent advances in protein separation and identification techniques have significantly improved proteomic approaches, leading to enhancement of the depth and breadth of proteome coverage.Proteomic signatures, specific for multiple diseases, including cancer and pre-invasive lesions, are emerging. This article combines, in a simple manner, relevant proteomic and OMICS clues used in the discovery and development of diagnostic and prognostic biomarkers that are applicable to all clinical fields, thus helping to improve applications of clinical proteomic strategies for translational medicine research. © 2012 Lopez et al.; licensee BioMed Central Ltd. Source

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