Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two proteins with phospholipase A(2) (PLA(2)) activity were purified to homogeneity from Bothrops leucurus (white-tailed-jararaca) snake venom through three chromatographic steps: Conventional gel filtration on Sephacryl S-200, ion-exchange on Q-Sepharose and reverse phase on Vydac C4 HPLC column. The molecular mass for both enzymes was estimated to be approximately 14 kDa by SDS-PAGE. The N-terminal sequences (48 residues) show that one enzyme presents lysine at position 48 and the other an aspartic acid in this position, and therefore they were designated blK-PLA(2) and blD-PLA(2) respectively. blK-PLA(2) presented negligible levels of PLA(2) activity as compared to that of blD-PLA(2). The PLA(2) activity of both enzymes is Ca(2+)-dependent. blD-PLA(2) did not have any effect upon platelet aggregation induced by arachidonic acid, ADP or collagen, but strongly inhibits coagulation and is able to stimulate Ehrlich tumor growth but not angiogenesis.
 ...
PMID:Purification and partial characterization of two phospholipases A2 from Bothrops leucurus (white-tailed-jararaca) snake venom. 1711 15

Camptothecin (CPT)-loaded nanoparticles were prepared using poly(dl-lactic acid) (PLA) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PEG-PPG-PEG), and examined for particle characteristics, in vitro release, pharmacokinetics and efficacy. The preparative condition, in which the ratio of PLA/PEG-PPG-PEG/CPT was 35/35/4 (w/w/w) and organic solvent (dichloromethane) was evaporated from the emulsion at 18 degrees C, gave the nanoparticles with the diameter of approximately 230nm, fairly high drug content (ca. 1.6% (w/w)) and stable entrapment of the drug, which were used for in vivo studies. After i.v. administration to normal rats, the nanoparticles showed slightly smaller AUC but much larger MRT as compared with CPT solution, and delivered the drug greatly to the surrounding tissues, in particular to the liver. When antitumor effect was examined by i.v. administration to mice bearing sarcoma 180 (S-180) solid tumor, the nanoparticles showed a significant suppression of tumor growth without body weight loss, and their effect was better than that of CPT solution. The PLA/PEG-PPG-PEG nanoparticles were considered potentially useful to enhance the efficacy of CPT, to which the high drug retention in the body and gradual drug release appeared to be importantly related.
 ...
PMID:Preparation and antitumor characteristics of PLA/(PEG-PPG-PEG) nanoparticles loaded with camptothecin. 1733 72

Neovascularization plays a critical role in the growth and metastatic spread of tumors and involves recruitment of circulating endothelial progenitor cells (EPC) from bone marrow as well as sprouting of preexisting endothelial cells. In this study, we examined if EPCs could promote tumor angiogenesis and would be an effective cellular target for an angiogenesis inhibitor, the recombinant kringle domain of tissue-type plasminogen activator (TK1-2). When TK1-2 was applied in the ex vivo culture of EPCs isolated from human cord blood, TK1-2 inhibited adhesive differentiation of mononuclear EPCs into endothelial-like cells. In addition, it inhibited the migration of ex vivo cultivated EPCs and also inhibited their adhesion to fibronectin matrix or endothelial cell monolayer. When A549 cancer cells were coimplanted along with ex vivo cultivated EPCs s.c. in nude mice, the tumor growth was increased. However, the tumor growth and the vascular density of tumor tissues increased by coimplanted EPCs were decreased upon TK1-2 treatment. Accordingly, TK1-2 treatment reduced the remaining number of EPCs in tumor tissues and their incorporation into the host vascular channels. In addition, overall expression levels of vascular endothelial growth factor (VEGF) and von Willebrand factor in tumor tissues were decreased upon TK1-2 treatment. Interestingly, strong VEGF expression by implanted EPCs was decreased by TK1-2. Finally, we confirmed in vitro that TK1-2 inhibited VEGF secretion of EPCs. TK1-2 also inhibited endothelial cell proliferation and migration induced by the conditioned medium of EPCs. Therefore, we concluded that EPCs, as well as mature endothelial cells, could be an important target of TK1-2.
 ...
PMID:Tumor angiogenesis promoted by ex vivo differentiated endothelial progenitor cells is effectively inhibited by an angiogenesis inhibitor, TK1-2. 1751 Apr 15

Tissue-type plasminogen activator (tPA) plays a major role in the fibrinolytic system. According to several reports, tPA may also have antiangiogenic properties, especially in combination with a free sulfhydryl donor (FSD). In the rat C6 glioma model, in vitro and in vivo tPA synthesis by glioma cells is enhanced by differentiation therapy. To address the antiangiogenic potential of tPA in this model, tPA was overexpressed in glioma tumors by ex vivo transduction of C6 cells with a lentiviral vector encoding tPA. The transduced cells were subcutaneously implanted into nude mice. Gene transfer allowed for efficient synthesis of tPA by the C6 tumors. Although the treatment of tPA+ tumor-bearing animals with the FSD captopril generated angiostatin in situ and reduced endothelial vascularization of the tumors, it had no effect on tumor growth. Alternative mechanisms could account for this lack of effect and consequently have important implications for vascular the treatment of glioblastoma.
 ...
PMID:Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model. 1853 15

The recombinant two-kringle domain of human tissue-type plasminogen activator (TK1-2) was found to inhibit angiogenesis and tumor growth. Recently, we found that TK1-2 inhibits adhesive differentiation of endothelial progenitor cells, and its contribution to tumor angiogenesis. In this study, we investigated the effects of TK1-2 on extracellular matrix-induced adhesion, signaling, and migration in order to understand the mechanism of action of TK1-2. When human umbilical vein endothelial cells were pretreated with TK1-2 and then allowed to adhere to immobilized fibronectin, vitronectin, or gelatin, cell adhesion to all the tested matrices decreased dose-dependently upon TK1-2 treatment. TK1-2 also inhibited the formation of actin stress fibers and focal adhesions upon attachment to each matrix. Moreover, fibronectin- and vitronectin-induced endothelial cell migration was dose-dependently inhibited by TK1-2. TK1-2 also suppressed fibronectin-induced ERK1/2 phosphorylation. Hence the results suggest that disturbance of extracellular matrix-induced adhesion, signaling, and migration of endothelial cells is involved in the anti-angiogenic activity of TK1-2.
 ...
PMID:The kringle domain of tissue-type plasminogen activator inhibits extracellular matrix-induced adhesion and migration of endothelial cells. 1877 98

Novel polylactic acid nanoparticles containing tanshinone IIA (TS-PLA-NPs) were synthesized by a single oil-in-water emulsion/solvent evaporation method. In this study, the optimized nanoparticles were characterized for morphology, mean particle size, zeta potential, entrapment efficiency, drug-loading content, X-ray diffractometer measurement, and in vitro release. The obtained nanoparticles were spherical and intact. The mean particle size was 192.5 nm with polydispersity index being 0.029 and zeta potential - 26.27 mV. The mean entrapment efficiency and loading of tanshinone IIA (TSIIA) in TS-PLA-NPs were 86.35 and 1.61%, respectively. The in vitro release study was performed at pH 7.4 using a dialysis membrane. Without initial burst effect, the TSIIA sustained release from TS-PLA-NPs for more than 7 days. The mean in vitro cumulative release percentage of TSIIA from TS-PLA-NPs vs. time curve fitted well with the Higuchi Equation (Q = 2.0365 + 13.564 x t(1/2), r = 0.9950). In pharmacokinetics and tissue distribution studies, the concentrations of TSIIA are higher in hepatoma and lower in blood, heart, kidney, spleen, and lung at 2 h after TS-PLA-NPs was administered via caudal vein. TS-PLA-NPs were effective in destroying the human liver cancer cells by the Mono-nuclear cell direct cytotoxicity assay (MTT) assay, and the growth-inhibitory effect of TS-PLA-NPs on human liver cancer cells was concentration and time dependent. The effect of TS-PLA-NPs on hepatoma in mice was also performed. The results of TS-PLA-NPs were markedly more effective than both of TSIIA and blank PLA nanoparticles in preventing tumor growth and increasing survival time of mice with hepatoma. This study provided support for the new paradigm, the application of TSIIA for the treatment of hepatoma.
 ...
PMID:Novel polymeric nanoparticles containing tanshinone IIA for the treatment of hepatoma. 1900 37

Transferrin (Tf), an iron-transporting serum glycoprotein, which binds to receptors expressed at the surface of most proliferating cells with particularly high expression on erythroblasts and cancer cells, was chosen as the ligand to develop BCNU-loaded biodegradable poly(D,L-lactic acid) nanoparticles (NPs) containing a ligand, which specifically binds to glioma cells, and their anti-tumor ability was evaluated using a C6 glioma model. In vitro drug release behavior demonstrated that BCNU-loaded PLA NPs show certain sustained release characteristics. NPs with low molecular weight PLA showed a higher burst effect and a significantly faster drug release from PLA samples. The biodistribution of Tf-coated nanoparticles investigated by 99Tc-labeled SPECT showed that the surface-containing transferrin PLA nanoparticles were concentrated in the brain and no radioactive foci could be found outside the brain. Inhibition of tumor growth in the C6 tumor-bearing animal model showed that BCNU-loaded PLA NPs had stronger cytotoxicity and prolonged the average survival time of rats. Especially when treated at an early stage with a higher dosage of NPs, the average survival time of rats was prolonged 88.37%. Furthermore, one rat maintained normal behavior continuously for an observation period of up to 60 days.
 ...
PMID:Growth inhibition against intracranial C6 glioma cells by stereotactic delivery of BCNU by controlled release from poly(D,L-lactic acid) nanoparticles. 1916 43

The fibrinolytic system, more appropriately referred to as the plasminogen activator system, controls not only the intravascular fibrin deposition but also participates in a wide variety of physiologic and pathologic processes. In cancer, the components of this system are involved in tumor growth, invasion and metastasis, through their effect on angiogenesis and cell migration. These components are found in most tumors and their expression signifies not only their function but also carries a prognostic value. Their expression is in turn modulated by cytokines and growth factors, many of which are up-regulated in cancer. Though both plasminogen activators, tPA and uPA, are expressed in tumor cells, uPA with its receptor (uPAR) is mostly involved in cellular functions, while tPA with its receptor annexin II on endothelial surface regulates intravascular fibrin deposition. Among the inhibitors of fibrinolysis, PAI-1 is a major player in the pathogenesis of many vascular diseases as well as in cancer. Therapeutic intervention, either using plasminogen activators or use of experimental inhibitor agents against PAI-1, has shown encouraging results in experimental tumors but not verified clinically. Information provided in this brief review is aimed to promote greater interest in the role of the plasminogen activator system in cancer.
 ...
PMID:The plasminogen activator system and cancer. 1917 91

Endoplasmic reticulum protein 29 (ERp29) is a novel endoplasmic reticulum (ER) secretion factor that facilitates the transport of secretory proteins in the early secretory pathway. Recently, it was found to be overexpressed in several cancers; however, little is known regarding its function in breast cancer progression. In this study, we show that the expression of ERp29 was reduced with tumor progression in clinical specimens of breast cancer, and that overexpression of ERp29 resulted in G(0)/G(1) arrest and inhibited cell proliferation in MDA-MB-231 cells. Importantly, overexpression of ERp29 in MDA-MB-231 cells led to a phenotypic change and mesenchymal-epithelial transition (MET) characterized by cytoskeletal reorganization with loss of stress fibers, reduction of fibronectin (FN), reactivation of epithelial cell marker E-cadherin and loss of mesenchymal cell marker vimentin. Knockdown of ERp29 by shRNA in MCF-7 cells reduced E-cadherin, but increased vimentin expression. Furthermore, ERp29 overexpression in MDA-MB-231 and SKBr3 cells decreased cell migration/invasion and reduced cell transformation, whereas silencing of ERp29 in MCF-7 cells enhanced cell aggressive behavior. Significantly, expression of ERp29 in MDA-MB-231 cells suppressed tumor formation in nude mice by repressing the cell proliferative index (Ki-67 positivity). Transcriptional profiling analysis showed that ERp29 acts as a central regulator by upregulating a group of genes with tumor suppressive function, for example, E-cadherin (CDH1), cyclin-dependent kinase inhibitor (CDKN2B) and spleen tyrosine kinase (SYK), and by downregulating a group of genes that regulate cell proliferation (eg, FN, epidermal growth factor receptor (EGFR) and plasminogen activator receptor (uPAR)). It is noteworthy that ERp29 significantly attenuated the overall ERK cascade, whereas the ratio of p-ERK1 to p-ERK2 was highly increased. Taken together, our results showed that ERp29 is a novel regulator leading to cell growth arrest and cell transition from a proliferative to a quiescent state, and reprogramming molecular portraits to suppress the tumor growth of MDA--MB--231 breast cancer cells.
 ...
PMID:Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal-epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells. 1986 66

Clinical and preclinical data indicate that immunotherapeutic interventions could induce immune responses capable of controlling or retard the tumor growth. However, immunotherapies need to be further optimized. We hypothesized that a more effective strategy for tumor eradication is to directly target the tumor microenvironment in order to generate a proinflammatory response and induce a localized antitumor immune response capable of eliminating the tumor cells. Nanoparticles have been proven to be an effective delivery system. In these studies we evaluated conjugated anti-RNEU and anti-CD40 antibodies onto PLA-(poly dl-lactic acid)-biodegradable nanoparticles (PLA-NP) for the induction of antitumor immune responses. The anti-neu/anti-CD40-NP were functional in vitro recognizing RNEU(+) tumors and activating dendritic cells. The delivery of anti-neu/anti-CD40-NP but not anti-neu-NP or anti-CD40-NP induced an antitumor response resulting in complete tumor elimination and generation of protective memory responses. The anti-neu/anti-CD40-NP specifically activated an antitumor response against RNEU(+) tumors but not against RNEU(-) tumors. The antitumor immune responses correlate with the induction of a Th1-proinflammatory response, reduction in the number of Tregs within the tumor and activation of a specific cytotoxic response. These results indicate that anti-neu/anti-CD40-NP with immunomodulatory properties are safe and can be used effectively as cancer vaccines strategy for the specific induction of antitumor immune responses.
 ...
PMID:Targeting the tumor microenvironment with anti-neu/anti-CD40 conjugated nanoparticles for the induction of antitumor immune responses. 1993 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>