Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P carinii, a significant increase in PA activity in cell lysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.
 ...
PMID:Plasminogen activator production in a rat model of Pneumocystis carinii pneumonia. 1159 34

Multidrug resistance is one of the main causes leading to failure of chemotherapy. Therefore, the rational design of targeting drug systems to reverse multidrug resistance is becoming an important strategy for cancer therapy. Herein, we present a novel copolymer-based nanoparticle that was size changeable and could realize the goal of precise drug controlled release under acidic conditions, and could overcome the multidrug resistance in breast cancer cells. This PCP/uPA nanosystem was formed through the crosslinking between chitosan (CS) and poly(N-isopropylacrylamide) (PNIPAM), followed by surface decoration with polyethylene glycol (mPEG) and a breast cancer targeting peptide uPA, which was then used to encapsulate metal complexes (RuPOP and Fe(PiP)3) to solve their bottleneck of low solubility and stability under physiological conditions. These multifunctional nanosystems (PCP-Ru/uPA and PCP-Fe/uPA) exhibited remarkable anticancer activity and could overcome the poor stability and low solubility of RuPOP and Fe(PiP)3. Noticeably, PCP-Ru/uPA reversed the multidrug resistance of drug-resistant MCF-7 (MCF-7R) human breast cancer cells by enhancing the cellular uptake of RuPOP by MCF-7R cells and inhibiting the expression of ABC family proteins. Furthermore, when PCP-Ru/uPA was at pH 5.3 with lysozyme, the release amount of RuPOP is the largest compared with pH at 5.3 or 7.4, and the release rate of RuPOP reached 75% at 48 h. In other words, the nanosystem with a pH-responsive effect swelled in an acidic environment and released free RuPOP in the lysosome of cancer cells efficiently, which triggered ROS up-regulation and induced apoptosis in MCF-7R cells. Taken together, this study presents a novel size changeable nanosystem for precise drug controlled release and efficient overcoming of cancer multidrug resistance.
 ...
PMID:Size changeable nanosystems for precise drug controlled release and efficient overcoming of cancer multidrug resistance. 3226 72