Plasminogen activators (PAs) are not used for thromboprophylaxis due to rapid clearance, bleeding, and extravascular toxicity. We describe a novel strategy that overcomes these limitations. We conjugated tissue-type PA (tPA) to a monoclonal antibody (mAb) against complement receptor type 1 (CR1) expressed primarily on human RBCs. Anti-CR1/tPA conjugate, but not control conjugate (mIgG/tPA), bou...

Induction of the B7 family molecules by 12-O-tetradecanoyl phorbol 13-acetate (TPA) has been reported, however, the mechanism by which TPA up-regulates these molecules remains poorly understood. In this study, the expression of B7-DC, -H1, -H2, and -H3 in response to TPA was markedly induced in K562 cells. TPA also induced activation of ERK, p38 mitogen-activated protein kinase (MAPK), JNK, pho...

Acute renal failure is often the result of ischemia-reperfusion (I/R) injury. Neutrophil influx is an important damaging event in I/R. Tissue-type plasminogen activator (tPA) not only is a major fibrinolytic agent but also is involved in inflammatory processes. A distinct upregulation of tPA after I/R, with de novo tPA production by proximal renal tubules, was found. For investigating the role ...

Clinically achievable concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA; 0.16-0.32 nM) and all-trans-retinoic acid (ATRA; 0.5-1 micro M) had a synergistic inhibitory effect on the growth of cultured LNCaP prostate cancer cells, and apoptosis was markedly stimulated. In additional studies, NCr immunodeficient mice received s.c. injection with LNCaP cells in Matrigel. After 4-6 weeks, m...

12-0-Tetradecanoylphorbol-13-acetate (TPA) stimulates the release of free choline from intact NG10815 cells into the medium, without affecting the release of phosphocholine (Liscovitch, M., Blusztajn, J. K., Freese, A., and Wurtman, R. J. (1987) Biochem. J. 241, 81-86). To test the hypothesis that this response reflects activation of cellular phospholipase D, via protein kinase C (Ca’+/phosphol...

Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single-target agents. Pomegranate fruit extract (PFE) derived from the tree Pun...

BACKGROUND In many case-control as well as epidemiological studies, increased lipoprotein(a) [Lp(a)] levels are considered to constitute an independent risk factor for premature coronary artery and cerebrovascular disease. Lp(a) resembles an LDL particle with an additional linked protein [apolipoprotein(a), apo(a)], whose molecular structure has been demonstrated to be homologous to the fibrino...

Plasminogen activator (PA) and PA inhibitor (PAI) antigen, activity, and mRNA were analyzed in the three layers of rat aorta, and the effect of endotoxin on PA and PAI was studied. All PA activity in aorta was identified as tissue-type PA (TPA) activity; no urokinase-type PA was detected. In the tunica adventitia TPA activity, TPA antigen, and TPA mRNA were detected, whereas in the tunica media...

BACKGROUND The urokinase-type (uPA) and tissue-type (tPA) plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen (Plg) to the active protease plasmin. Based on the efficient activation of plasminogen when uPA is bound to its receptor (uPAR) and on the role of uPA in plasmin-mediated liver repair, we hypothesized that uPA requires uPAR for efficient liver ...