ABSTRACT
Modulation of the balance between pro- and antiangiogenic factors holds great promise for the treatment of a broad spectrum of human disease ranging from ischemic heart disease to cancer. This requires both the identification of angiogenic regulators and their efficient delivery to target organs. Here, we demonstrate the use of a noncatalytic fragment of matrix metalloproteinase 2 (termed PEX) delivered by lentiviral vectors in different angiogenesis models. Transduction of human endothelial cells with PEX virus suppressed endothelial invasion and formation of capillary-like structures without affecting chemotaxis in vitro. Lentiviral delivery of PEX blocked basic fibroblast growth factor-induced matrix metalloproteinase 2 activation and angiogenesis on chicken chorioallantoic membranes. PEX expression also inhibited tumor-induced angiogenesis and tumor growth in a nude mouse model. Thus, our study shows that lentiviral vectors can deliver sufficient quantities of antiangiogenic substances to achieve therapeutic effects in vivo.
Subject(s)
Integrins/physiology , Matrix Metalloproteinase 2/genetics , Neovascularization, Physiologic , Allantois/blood supply , Animals , Chick Embryo , Chorion/blood supply , Endothelium, Vascular/cytology , Endothelium, Vascular/growth & development , Endothelium, Vascular/metabolism , Female , Gene Expression , Humans , Matrix Metalloproteinase 2/physiology , Melanoma/blood supply , Melanoma/pathology , Melanoma/prevention & control , Mice , Mice, Nude , Neoplasm Transplantation , Peptide Fragments/genetics , TransfectionSubject(s)
Community Health Centers/organization & administration , Community Health Nursing/organization & administration , Health Promotion/organization & administration , Models, Organizational , Program Development/methods , Cooperative Behavior , Humans , Indiana , Primary Health Care/organization & administration , Program EvaluationABSTRACT
The purpose of this study was to develop and evaluate the psychometric properties of the Cognitive Appraisal of Health Scale (CAHS). The CAHS was developed to measure multiple dimensions of primary and secondary appraisals associated with health-related events. Items were generated for primary appraisal scales of threat, harm/loss, challenge, and benign/irrelevant, and secondary appraisal coping options and resources. The CAHS was tested in a sample of 201 women with breast cancer. Following tests of item analysis, reliability, and construct and concurrent validity, the CAHS was reduced to 28 items. During factor analysis a four-factor solution explained 60% of the total variance and represented the proposed primary appraisal dimensions. Intercorrelations among primary and secondary appraisals were consistent with theory (p < 0.01). Support for concurrent validity was provided by the clinically relevant differences in appraisal by time since diagnosis. The primary appraisal scale estimates of internal consistency (theta) were all greater that .70. Findings indicated beginning support for reliability and validity of the CAHS as a measure of cognitive appraisal for health-related events.
