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Laboratory of Cellular and Molecular Biology and Laboratory of Cardiovascular Science, National Institute of Aging, National Institutes of Health, Baltimore, Maryland 21224, USA; Medical Breast Cancer Section, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; and Laboratorio di Patologia Vascolare,(More)
Myocyte cell loss is a prominent and important pathogenic feature of cardiac ischemia. We have used cultured neonatal rat cardiac myocytes exposed to prolonged hypoxia as an experimental system to identify critical factors involved in cardiomyocyte death. Exposure of myocytes to hypoxia for 48 h resulted in intranucleosomal cleavage of genomic DNA(More)
The tumor suppressive effect of p53 is believed to be rooted in its two primary functions: the implementation of cellular growth arrest and the execution of apoptotic cell death. While p53-regulated expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) appears to be central for the implementation of G1 arrest, the participation of(More)
The mechanism by which p53 activates apoptosis in various cell systems is unknown. In the absence of an external death stimulus, p53 and p53-dependent genes, bcl-2 and bax, cannot trigger apoptosis. However, p53 may enhance not only transcription of bax and repress bcl-2, but also may upregulate the local renin-angiotensin system, inducing the formation and(More)
The use of replication-deficient adenoviral vectors in gene therapy may become a powerful method to achieve efficient but safe transfer of anti-tumor agents. Introduction of the wild-type p53 gene into tumor cells has, in general, been associated with growth suppression. In this study, infection of androgen-independent human prostate Tsu-pr1 cells lacking(More)
Gene transfer with replication-deficient recombinant adenovirus (Ad) vectors may provide a novel approach to the treatment of some cardiac disorders. The relative efficiency of intramyocardial vs intracoronary Ad vector injection in transducing myocardial cells remains to be determined. Further, Ad vectors are associated with localized inflammation, and(More)
Gene therapy with the tumor suppressor gene p53 induces cancer cell apoptosis in vitro and in vivo and inhibits tumor growth in nude mice. We hypothesized that, in addition to cancer cell apoptosis, a replication-deficient adenovirus vector which carries the cDNA for human wild-type p53 (AdCMV.p53) may also modulate endothelial cell function and inhibit(More)
AIM Our study aims to evaluate the efficiency of short-term therapy with alprostadil (a PGE molecular derivative) on patients affected by critical ischemia of the lower limbs and unsuitable for surgical revascularization. The study was carried out on two groups of patients treated with the traditional long-term or a short-term protocol respectively. (More)
Gene transfer techniques may provide efficient treatment for a variety of malignant neoplasms. A replication-deficient adenovirus (Ad) vector which carries the cDNA for wild-type p53 (AdCMV.p53) was tested for its in vitro and in vivo effects on the growth of murine melanoma cell line B16-G3.26 and human melanoma cell line SK-MEL-24. The growth of B16-G3.26(More)
OBJECTIVE The antiapoptotic effect of p21(Waf1/Cip1/Sdi1) (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia. METHODS In vitro: Cells were cultured without serum and in the presence of cobalt chloride to(More)