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)

In this study DMSO (dimethylsulphoxide) was used as a tool to test the significance of in vitro modifications of procoagulant and fibrinolytic activity of tumor cells for their in vivo metastatic ability. B16 melanoma cells were chosen as the experimental model. After four days' treatment DMSO increased both the procoagulant and fibrinolytic (plasminogen activator) activity of B16 melanoma cells in a dose-related manner. DMSO treated cells showed significantly greater lung colonizing ability than untreated cells. Our results indicate that DMSO treatment in vitro can modulate procoagulant and fibrinolytic activity and the metastatic ability of B16 melanoma cells; however a direct causal relationship between these in vitro and in vivo effects remains to be established.
 ...
PMID:DMSO-induced changes in the procoagulant and fibrinolytic activity of B16 melanoma cells: influence on lung colony formation. 337 75

Dimethylsulfoxide, butyrate and retinoic acid, agents which induce differentiation of certain malignant cells, were examined for their effect on the activity of plasminogen activator (PA) of serumless conditioned medium (CM) of two human renal carcinoma cell lines. All three agents produced a decrease in PA activity. More than 90% of the PA was secreted in latent form, and this was not altered by the agents. Active PA components of Mr 52,000 and 93,000 were identified in cell secretions by zymography. In the presence of DMSO or butyrate the Mr 52,000 component was markedly reduced. Reversibility of the effect on PA was demonstrated for both DMSO and retinoic acid with activity of CM returning to control level after removal of the agent. That the effect was temporary agrees with most observations of the effects of these and similar agents on cells from solid tumors.
 ...
PMID:Modulation of secreted plasminogen activator activity of human renal carcinoma cells by dimethylsulfoxide, butyrate and retinoate. 354 47

Human carcinoma HEp-3 lost its tumorigenic and metastatic potential upon prolonged culture in vitro. This change was accompanied by a reduced production of plasminogen activator (PA) of the urokinase type (uPA), which is secreted by HEp-3 cells, a change in response to effectors that modulate uPA production, and an alteration of cell morphology. Similar but more rapid changes occurred when malignant HEp-3 cells were exposed to dimethyl sulfoxide (DMSO). uPA activity in the culture medium dropped below 50% of the control level within 6 h after the addition of DMSO and became undetectable after 24 h of treatment. This drop in uPA activity was not caused by an increased production of PA inhibitors. The cell-associated uPA decreased to 25 to 30% of the control level within 6 h of DMSO treatment and remained at this level for at least 96 h; the reduced uPA production was partially accounted for by a rapid decrease in the functional and chemical concentration of uPA mRNA. In contrast, the concentrations of most of the abundant mRNA species did not appear to be significantly affected, and cell growth was only slightly inhibited in the presence of DMSO. Malignant HEp-3 cells treated with DMSO responded to cholera toxin with an enhanced production of uPA, and their morphology became indistinguishable from that of nonmalignant HEp-3 cells grown in vitro for prolonged periods of time. All of the above changes were fully and rapidly reversible. The inhibitory effect of DMSO on PA production appears to be specific for uPA of human cell lines.
 ...
PMID:Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin. 383 48

Treatment of low-metastatic Lewis lung carcinoma cells (P-29) with dimethylsulfoxide (DMSO) in vitro enhanced their lung-colonizing ability. The effects of other highly polar compounds on the lung-colonizing ability of P-29 cells were examined. The following compounds were found to enhance the lung-colonizing ability of the cells: acetamide, N-methylacetamide, N-methylformamide, N,N-dimethylformamide, piperidone and hexamethylphosphoric triamide. Treatment of P-29 cells with DMSO or other polar compounds resulted in increases in activities of degradative enzymes, such as cathepsin B and plasminogen activator. The increases in cathepsin B and plasminogen activator activities were apparent after a 24 h treatment with DMSO and were suppressed by simultaneous treatment with cycloheximide, which suggested that they were due to syntheses of new proteins. DMSO-treated P-29 cells degraded [3H]leucine-labelled subendothelial matrix much more than did untreated cells. P-29 cells treated with DMSO or other polar compounds became attached to culture dishes more rapidly and were more resistant to detachment by trypsin treatment than untreated cells. A significant correlation was found between the degrees of adhesiveness of P-29 cells treated with various polar compounds and their lung-colonizing abilities.
 ...
PMID:Enhancement of lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells by treatment with highly polar compounds. 654 Feb 47

Treatment of low-metastatic Lewis lung carcinoma cells (P-29) with dimethyl sulfoxide in vitro enhanced their lung-colonizing ability. The concentration of dimethyl sulfoxide used delayed the in vitro growth of P-29 cells but was not cytotoxic. The arrest and retention in the lung of untreated and dimethyl sulfoxide-treated P-29 cells labeled with 5-[125I]iodo-2'-deoxyuridine after injecting them into a tail vein of syngeneic mice were examined. Dimethyl sulfoxide-treated P-29 cells were trapped in the lung more than untreated cells and were cleared from the lungs more slowly than untreated cells. Treatment of P-29 cells with dimethyl sulfoxide resulted in the increase in their homotypic aggregation and adhesion to plastic culture dishes, monolayers of endothelial cells, and a subendothelial extracellular matrix. This treatment also increased significantly their activities of degradative enzymes, such as glycosidases and cathepsin B, and their production of plasminogen activator. These results indicate that the enhanced lung-colonizing ability of P-29 cells treated with dimethyl sulfoxide is due to the increase in adhesiveness, resulting in arrest and retention of the cells in the lung of the host and in the increase in their degradative enzyme activities. The enhancing effect of dimethyl sulfoxide on the lung-colonizing ability of P-29 cells was found to be reversible.
 ...
PMID:Enhanced metastatic potential of cloned low-metastatic Lewis lung carcinoma cells treated in vitro with dimethyl sulfoxide. 669 98

A bioresorbable aliphatic polyester was synthesized by bulk copolymerization of a 1/1 M/M L,L-lactide/epsilon-caprolactone mixture using zinc metal as initiator. The actual composition of the copolymer was found to be 1.5/1 as deduced from 1H NMR spectra obtained in DMSO-d6 solutions where higher resolution was obtained as compared with chlorinated solvents. Resonances due to L-lactyl units (L) exhibited triads stereosensitivity, epsilon-oxycaproyl units (C) being sensitive to dyads. Average lengths of both poly(lactic acid) and polycaprolactone sequences were evaluated and showed the presence of rather long PLA blocks. Furthermore, no CLC triad signal was found, suggesting the absence of transesterification rearrangements. 10 x 10 x 2 mm specimens made of the copolymer were allowed to age in isoosmolar pH = 7.4 phosphate buffer at 37 degrees C. Degradation was monitored by various analytical techniques such as SEC, X-ray diffractometry, DSC, and 1H NMR. Data were compared with the behaviour of PCL and PLA homopolymers allowed to age under similar conditions. Crystallinity and composition changes are discussed in terms of preferential degradation in L- and C-containing amorphous domains, crystallized long PLA blocks being much more resistant.
 ...
PMID:Structural characterization and hydrolytic degradation of a Zn metal initiated copolymer of L-lactide and epsilon-caprolactone. 899 92

The prognosis of patients with metastasised follicular thyroid carcinoma (FTC) is limited, necessitating the search for new treatment options. Beneficial effects of retinoids have been suggested in thyroid cancer and the present study was performed to investigate the effects of retinoic acid (RA) on important determinants of metastatic behaviour in FTC: the disengagement of tumour cells from the primary tumour and the degradation of extracellular matrix, focusing on the role of the plasmin activation system and the integrin and E-cadherin families of attachment molecules. Three FTC cell lines were studied: FTC-133, derived from the primary tumour; and FTC-236 and FTC-238, derived from metastases. FTC cell lines were cultured with 0.1, 1 and 10 microM 13-cis-RA or with the solvent DMSO for 1 and 5 days. Extracellular matrix degradation by these cell lines was studied by assessing the 48-h release of radioactivity from (35)S-methionine labelled extracellular matrix proteins synthesised by the MC3T3 cell line coated onto plastic. The involvement of constituents of the plasmin activation system was investigated by semi-quantitative RT-PCR and zymography. Attachment to extracellular matrix was studied by determining the number of adhering FTC cells to extracellular matrix coated onto plastic, 3 h after seeding. The involvement of attachment molecules was studied by RT-PCR with primers for integrin subclasses and E-cadherin and immunofluorescence for E-cadherin. Five days culturing with 10 microM RA reduced the degradation of extracellular matrix significantly in all cell lines: FTC-133 by 35%, FTC-236 by 74% and FTC-238 by 31%. Zymography revealed diminished activity of urokinase type plasminogen activator (uPA) in FTC-236 and FTC-238, but not in FTC-133 cultured with RA. mRNA expression of the uPA receptor was diminished in FTC-236. In the attachment assay, 10 microM RA for 5 days increased the number of adherent cells to extracellular matrix significantly by 91% in FTC-133, 64% in FTC-236 and 87% in FTC-238. No effects of RA on integrin or E-cadherin mRNA expression were observed. Immunofluorescence, however, revealed enhanced organisation of E-cadherin along the cell membrane by RA treatment. In conclusion, the present study demonstrates beneficial effects of RA on important determinants of metastatic behaviour in FTC cell lines, e.g. decreased degradation of extracellular matrix which may in part be explained by effects on the plasmin activation system and enhanced attachment to extracellular matrix. These findings may add to the explanations for beneficial effects of retinoids in thyroid cancer.
 ...
PMID:Beneficial effects of retinoic acid on extracellular matrix degradation and attachment behaviour in follicular thyroid carcinoma cell lines. 1105 36

When co-precipitated with amphiphilic copolymers from DMSO, poly(D,L-lactide) (PLA) can be readily converted into stable sub-200 nm nanoparticles by addition of an aqueous phase, free of any polymeric stabilizers such as poly(vinyl alcohol) or Poloxamer. In this work, the ability of random poly(methyl methacrylate-co-methacrylic acid) copolymers (PMMA-co-MA) to stabilize PLA nanoparticles was demonstrated, and the properties of PLA/PMMA-co-MA nanoparticles were investigated. When co-precipitated with PMMA-co-MA, PLA was totally converted into nanoparticles using a polymer concentration in DMSO (Cp) below 17.6 mg ml(-1), and a PMMA-co-MA proportion above a critical value depending on the content of MA repeating units (X). For instance, the lowest PMMA-co-MA proportion required was 0.9 mg mg(-1) PLA for X = 12%, and 0.5 mg mg(-1) PLA for X = 25% (for C(PLA) = 16 mg ml(-1) DMSO). The nanoparticle diameter was essentially independent of X, the proportion of PMMA-co-MA, and the PLA molecular weight, except for oligomers for which the nanoparticle diameter was smaller. It decreased when the organic phase was diluted (126 +/- 13 nm for Cp = 17.6 mg ml(-1), and 81 +/- 5 nm for C(P) = 5.6 mg ml(-1)). The time-dependence of the stability and the degradation of PLA/PMMA-co-MA nanoparticles was discussed. One of the main advantages of this technique is the ability to control surface properties and to bring functional groups to otherwise non-functionalized PLA nanoparticles. To illustrate this, a conjugate of PMMA-co-MA25 and biotin was synthesized, and used to prepare biotinylated nanoparticles that could be detected by fluorescence and transmission electron microscopy after infiltration into ligatured rat small intestine.
 ...
PMID:Preparation of poly(D,L-lactide) nanoparticles assisted by amphiphilic poly(methyl methacrylate-co-methacrylic acid) copolymers. 1143 78

Fully biodegradable and surface-functionalized poly(D,L-lactide) (PLA) nanoparticles have been prepared by a co-precipitation technique. Novel amphiphilic random copolyesters P(CL-co-gammaXCL) were synthesized by controlled copolymerization of epsilon-caprolactone and epsilon-caprolactone substituted in the gamma-position by a hydrophilic X group, where X is either a cationic pyridinium (gammaPyCL) or a non-ionic hydroxyl (gammaOHCL). Nanoparticles were prepared by co-precipitation of PLA with the P(CL-co-gammaXCL) copolyester from a DMSO solution. Small amounts of cationic P(CL-co-gammaPyCL) copolymers are needed to quantitatively form stable nanoparticles (ca. 10 mg/ 100 mg PLA), although larger amounts of non-ionic P(CL-co-gammaOHCL) copolymers are needed (> or = 12.5 mg/ 100 mg PLA). Copolymers with a low degree of polymerization (ca. 40) are more efficient stabilizers, probably because of faster migration towards the nanoparticle-water interface. The nanoparticle diameter decreases with the polymer concentration in DMSO, e.g. from ca. 160 nm (16 mg/ml) to ca. 100 nm (2 mg/ml) for PLA/P(CL-co-gammaPyCL) nanoparticles. Migration of the P(CL-co-gammaXCL) copolyesters to the nanoparticle surface was confirmed by measurement of the zeta potential, i.e. ca. +65 mV for P(CL-co-gammaPCL) and -7 mV for P(CL-co-gammaOHCL). The polyamphiphilic copolyesters stabilize PLA nanoparticles by electrostatic or steric repulsions, depending on whether they are charged or not. They also impart functionality and reactivity to the surface, which opens up new opportunities for labelling and targeting purposes.
 ...
PMID:Amphiphilic copolymers of epsilon-caprolactone and gamma-substituted epsilon-caprolactone. Synthesis and functionalization of poly(D,L-lactide) nanoparticles. 1263 71

Entubulation repair of peripheral nerve injuries has a lengthy history. Several experimental and clinical studies have explored the effectiveness of many biodegradable and non-degradable tubes with or without addition of molecules and cells. The main objective of the present study was to develop an economical and also an easy way for culturing a neural cell line which was capable of growing, differentiating and producing locally nerve growth factors that are otherwise extremely expensive, inside 90 PLA/10 PLG nerve guides. For this purpose the authors have chosen the N1E-115 cell line, a clone of cells derived from mouse neuroblastoma C-1300 with the perspective of using this differentiated cellular system to cover the inside of 90 PLA/10 PLG nerve guides placed to bridge a gap in the rat sciatic nerve experimental model. The N1E-115 cells proliferate in normal culture medium but undergo neuronal differentiation in response to DMSO. Upon induction of differentiation, proliferation of N1E-115 cells ceases, extensive neurite outgrowth is observed and the membranes become highly excitable. While it is known that Ca2+ serves as an important intracellular signal for various cellular processes, such as growth and differentiation. It is also known that can be toxic to cells and is involved in the triggering of events leading to excitotoxic cell death in neurons. The [Ca2+]i in non-differentiated N1E-115 cells and after distinct periods of differentiation, have been determined by the epifluorescence technique using the Fura-2-AM probe. The results of this quantitative assessment revealed that N1E-115 cells which undergo neuronal differentiation for 48 hours in the presence of 1.5% DMSO are best qualified to be used to cover the interior of the nerve guides since the [Ca2+]i was not found to be elevated indicating thus that the onset the cell death processes was not occurred.
 ...
PMID:Determination of the intracellular Ca2+ concentration in the N1E-115 neuronal cell line in perspective of its use for peripheric nerve regeneration. 1630 61


1 2 3 Next >>