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

Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in three vehicles: poly(D,L-lactic acid) (PLA) nanoparticles, polyethylene glycol (PEG)-coated nanoparticles and a Cremophor EL (CRM) oil-water emulsion. Nanoparticles were prepared by the salting-out procedure. Biodistribution of the dye was assessed by fluorescence in EMT-6 mammary tumour bearing mice after intravenous injection of 1 mumol kg-1 ZnPcF16. Plain nanoparticles were rapidly retained by the reticuloendothelial system (RES) as reflected by the low area under the blood concentration-time curve (AUC0-168, 57 micrograms h g-1). Little tumour uptake of the dye was observed with this formulation. In contrast, PEG-coated nanoparticles displayed a reduced RES uptake, leading to significantly higher blood levels over an extended period (t1/2 30 h; AUC 0-168 227 micrograms h g-1) and enhanced tumour uptake. At 48 h post injection, tumour to skin and tumour to muscle concentration ratios reached 3.5 and 10.8, respectively. Blood levels of ZnPcF16 after administration as a CRM emulsion decreased faster than with PEG-coated nanoparticles (t1/2 12 h), but since no early liver uptake was observed, the AUC0-168 and the tumour uptake were only slightly lower. However, with the CRM formulation, a late liver uptake was observed, reaching 51% of the injected dose after 7 days.
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PMID:PEG-coated poly(lactic acid) nanoparticles for the delivery of hexadecafluoro zinc phthalocyanine to EMT-6 mouse mammary tumours. 749 87

Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second-generation sensitizer for the photodynamic therapy (PDT) of cancer, was formulated in polyethylene-glycol-coated poly(lactic acid) nanoparticles (PEG-coated PLA-NP) and tested in EMT-6 tumour-bearing mice for its photodynamic activity. The tumour response was compared to that induced by the same dye formulated as a Cremophor EL (CRM) emulsion. Formulation in the biodegradable NP improved PDT response of the tumour while providing prolonged tumour sensitivity towards PDT.
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PMID:Photodynamic therapy of tumours with hexadecafluoro zinc phthalocynine formulated in PEG-coated poly(lactic acid) nanoparticles. 864 56

A photosensitizer, meso-tetra(hydroxyphenyl)porphyrin (p-THPP) was incorporated into sterile submicronic nanoparticles of poly(D,L-lactide-co-glycolide) (50:50 and 75:25 PLGA) and poly(D,L-lactide) (PLA). With all polymers used, sub-130 nm p-THPP-loaded nanoparticles with similar drug loadings and entrapment efficiencies were produced using the emulsification-diffusion technique. The photodynamic activity (photocytotoxicity) of these nanoparticles was evaluated on EMT-6 mammary tumour cells in comparison with the free drug. The influence of drug concentration (3-10 microg/ml), incubation time (5-60 min) and light dose (6-9 J/cm(2)) on p-THPP photocytotoxic efficiency was investigated. With all p-THPP formulations tested, cell viability decreased with increasing values of these parameters. The beneficial effect of nanoencapsulation compared to free drug was highlighted at drug concentrations up to 6 microg/ml and short incubation times (15-30 min). The most important photocytotoxicity was observed with 50:50 PLGA nanoparticles allowing low drug doses and short drug administration-irradiation intervals for local photodynamic therapy.
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PMID:Enhanced photodynamic activity of meso-tetra(4-hydroxyphenyl)porphyrin by incorporation into sub-200 nm nanoparticles. 1265 35

The cellular uptake, localization and efflux of meso-tetra-(4-hydroxyphenyl)porphyrin (p-THPP)-loaded nanoparticles have been studied in EMT-6 tumor cells. The effect of blood serum on photocytotoxicity has also been evaluated. Sub-130 nm nanoparticles based on poly(D,L-lactide-co-glycolide) (PLGA) (50:50 PLGA and 75:25 PLGA) and poly(D,L-lactide) (PLA) have been examined in comparison with free p-THPP. For all formulations tested, uptake of photosensitizer into cells was dependent on concentration, time and temperature. All nanoparticulate formulations accumulated within the cells to a greater extent relative to free drug. Indeed, the fluorescence intensities measured on EMT-6 cells treated with p-THPP-loaded nanoparticulate formulations were at least two-fold higher than those obtained with free dye. Furthermore, the highest accumulation level was found with PLGA nanoparticles. Fluorescence microscopy revealed that endocytosis is a major intracellular sequestration mechanism of these p-THPP formulations and that these were localized into early and late endosomes. The efflux study performed on both nonirradiated and irradiated cells indicated that free and p-THPP-loaded nanoparticles gradually escaped from EMT-6 cells as a function of time. This was more pronounced when cells were treated with nanoparticles and irradiated, reflecting important photodamage. It was also found that regardless of the nanoparticulate formulations tested, p-THPP photocytotoxicity was influenced by the concentration of the serum.
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PMID:Encapsulation of p-THPP into nanoparticles: cellular uptake, subcellular localization and effect of serum on photodynamic activity. 1287 Aug 50

Although the introduction of t-PA (tissue plasminogen activator) was considered radical treatment for acute cerebral ischemic disease, the actual number of cases for such administration was limited in Japan for many reasons; one such reason was related to the ability of EMT (emergency medical technician) paramedics to transport patients to the proper hospital for treatment within 2 hours of onset. From this point of view, the Committee of the Prehospital Stroke Life Support (PSLS) of the Japanese Society for Emergency Medicine (JSEM) developed an original standard for prehospital treatment of stroke. In this paper, the author provides an overview of PSLS and the half-day practical course, which has been widely disseminated over a short period of time.
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PMID:Introduction of the standard prehospital stroke life support (PSLS) training of EMS paramedics for the prehospital management of cerebrovascular disease in Japan. 2022 8

In solid tumours, elevated interstitial fluid pressure (osmotic and hydrostatic pressure) is a barrier to drug delivery and correlates with poor prognosis. Glioblastoma (GBM) further experience compressive force when growing within a space limited by the skull. Caveolae are proposed to play mechanosensing roles, and caveola-forming proteins are overexpressed in GBM. We asked whether caveolae mediate the GBM response to osmotic pressure. We evaluated in vitro the influence of spontaneous or experimental down-regulation of caveola-forming proteins (caveolin-1, CAVIN1) on the proteolytic profile and invasiveness of GBM cells in response to osmotic pressure. In response to osmotic pressure, GBM cell lines expressing caveola-forming proteins up-regulated plasminogen activator (uPA) and/or matrix metalloproteinases (MMPs), some EMT markers and increased their in vitro invasion potential. Down-regulation of caveola-forming proteins impaired this response and prevented hyperosmolarity-induced mRNA expression of the water channel aquaporin 1. CRISPR ablation of caveola-forming proteins further lowered expression of matrix proteases and EMT markers in response to hydrostatic pressure, as a model of mechanical force. GBM respond to pressure by increasing matrix-degrading enzyme production, mesenchymal phenotype and invasion. Caveola-forming proteins mediate, at least in part, the pro-invasive response of GBM to pressure. This may represent a novel target in GBM treatment.
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PMID:A role for caveola-forming proteins caveolin-1 and CAVIN1 in the pro-invasive response of glioblastoma to osmotic and hydrostatic pressure. 3206 71