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)

Poly(DL-lactic acid) (PLA) microspheres containing a neurotensin analogue [NA; H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt.3HCl] were prepared by a novel oil-in-water (o/w) solvent evaporation method, and the release behaviors were evaluated in vitro. About 20% of the loaded NA was released initially, and the subsequent release lasted for a month from microspheres prepared with PLA of molecular weight 2000 (PLA 2000). A smaller initial release from PLA 4000 and PLA 6000 microspheres was found, but a lag time of 2-3 weeks during which the drug was not released was observed with PLA 4000 and PLA 6000 microspheres. The addition of relatively hydrophilic monoglycerides decreased the lag time, and a fairly constant release of NA was achieved. The pharmacokinetic behavior of NA from PLA 2000 microspheres was studied in rats. The release of the drug after a subcutaneous injection exhibited pseudo-zero-order kinetics for 1 month. The initial release of the drug from the microspheres was reflected in a sharp increase of the plasma levels of the de-ester form of NA [H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OH], and the subsequent steady-state levels agreed well with the predicted levels obtained from analysis of constant-infusion kinetics.
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PMID:In vitro and in vivo release of poly(DL-lactic acid) microspheres containing neurotensin analogue prepared by novel oil-in-water solvent evaporation method. 140 28

The thermal characteristics of poly (DL-lactic acid) (DL-PLA) microspheres containing a hexapeptide (NA: H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt) with neurotensin activity were investigated. PLA microspheres with a drug content of 1.5-11.0% were prepared by a novel o/w (oil-in-water) solvent evaporation method. Both DL-PLA and NA were amorphous in form, and an increase in heat capacity at glass transition temperature (Tg) of the polymer was observed in DL-PLA microspheres containing NA. The Tg of DL-PLA (PLA2000 bulk) was 307.8 K, while Tg of microspheres containing NA (content 6.0%) shifted to 321.2 K. The Tg of PLA2000 microspheres was found to increase with an increase in the content of NA, and its increasing tendency reached a plateau at an NA content of greater than 6%. The apparent activation energy of glass transition of PLA2000 bulk and the microspheres was calculated to be 86.3 and 99.3 kcal/mol, respectively. As a result of the release test after storage at 4 degrees C and 40 degrees C for 1 month, nearly the same release profiles of NA from PLA2000 microspheres were found. The release rate of NA after the initial release became slow after storage at 45 degrees C for 1 month. This may be attributed mainly to a decrease in surface area caused by the formation of agglomerates of PLA2000 microspheres under conditions near Tg.
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PMID:Thermal characteristics of poly (DL-lactic acid) microspheres containing neurotensin analogue. 146 21

Resistance formation is one of the major hurdles in cancer therapy. Metronomic anti-angiogenic treatment of xenografted prostate cancer tumors in severe combined-immunodeficiency (SCID) mice with cyclophosphamide (CPA) results in the appearance of resistant tumors. To investigate the complex molecular changes occurring during resistance formation, we performed a comprehensive gene expression analysis of the resistant tumors in vivo. We observed a multitude of differentially expressed genes, e.g., PAS domain containing protein 1, annexin A3 (ANXA3), neurotensin, or plasminogen activator tissue (PLAT), when comparing resistant to in vivo passaged tumor samples. Furthermore, tumor cells from in vivo and in vitro conditions showed a significant difference in target gene expression. We assigned the differentially expressed genes to functional pathways like axon guidance, steroid biosynthesis, and complement and coagulation cascades. Most of these genes were involved in anti-coagulation. Up-regulation of anticoagulatory ANXA3 and PLAT and down-regulation of PLAT inhibitor serpin peptidase inhibitor clade A were validated by quantitative real-time polymerase chain reaction. In contrast, coagulation factor F3 was upregulated, accompanied by the expression of an altered gene product. These findings give insights into the resistance mechanisms of metronomic CPA treatment, suggesting an important role of anti-coagulation in resistance formation.
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PMID:A Comprehensive Gene Expression Analysis of Resistance Formation upon Metronomic Cyclophosphamide Therapy. 2341 11