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)

This investigation was undertaken to examine the extent to which leukemic cell functions are susceptible to regulation in vitro and to investigate their heterogeneity in this regard. Since plasminogen activator release is known to be a modulatable cellular function that can be influenced by antiinflammatory steroids and tetradecanoyl phorbol acetate (TPA), the effect of these two compounds on the secretion of urokinase- or tissue-type enzymes by leukemic cells was studied. The release of both enzyme species could be stimulated or suppressed by these substances by mechanisms that were inhibitable by actinomycin-D and hence required transcription of new mRNA. Plasminogen activator release by cells from 41/45 patients with AML was either stimulated or inhibited by 10(-7) M dexamethasone, implying that most AML cells possess glucocorticoid receptors. In 26/45 cases, the enzyme was inhibited by this steroid to less than 25% of control values. Pronounced inhibition of this degree was not encountered with normal polymorphonuclear leukocytes. Plasminogen activator secretion by AML cells was profoundly inhibited in 20/41 cases by 1 ng/ml TPA and stimulated in 8/41 cases. Leukemic blasts varied considerably in their response to dexamethasone and TPA. Plasminogen activator release should prove a sensitive means of monitoring the responses of AML cells to biologically active compounds.
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PMID:The effects of dexamethasone and tetradecanoyl phorbol acetate on plasminogen activator release by human acute myeloid leukemia cells. 657 77

The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells.
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PMID:Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA-R) in acute myeloid leukemia cells. 851 88

A biodegradable, pH-sensitive amphiphilic co-polymer, o-(2-aminoethyl)-o'-methylpolyethylene glycol/1-(3-aminopropyl)imidazole/lactic acid oligomers-g-polyaspartamide (MPEG/API/LAs-g-PASPAM), was synthesized. The hydrophobic biodegradable poly (lactic acid) (PLA), the hydrophilic MPEG and the pH-sensitive API were successfully introduced into the biodegradable polysuccinimide (PSI) backbone by grafting. In its synthesis, the feed ratio of MPE to PLA was varied to provide different amphiphilic balances. FT-IR and (1)H-NMR spectroscopy were used to identify the chemical structure of the MPEG/API/LAs-g-PASPAM co-polymers synthesized. Tens to a few hundreds of nanometer-scaled aggregates, appropriate for intracellular drug-carrier applications, were developed in the simulated buffer solution, and their self-assembling behavior was significantly affected by the environmental pH. The size and morphology of self-aggregates were investigated using dynamic light scattering and transmission electron microscopy. The buffering effect was observed in the endosomal pH range. The drug loading and release experiments were conducted for a series of co-polymer aggregate systems, and it was noted that the release behavior was mostly governed by diffusion. The biodegradable kinetics was also studied to ascertain the drug-release mechanism.
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PMID:pH-sensitive amphiphilic biodegradable graft co-polymer aggregates based on polyaspartamide for intracellular delivery. 2172 24

Sudden chest pain, dyspnea, and tachypnea occurred in a 21-year-old female who was undergoing induction chemotherapy under a diagnosis of minimally differentiated acute leukemia (M0). The arterial blood gas (ABG) tensions were decreased (PO2 71.6 mm Hg, PCO2 23.7 mm Hg), and an electrocardiogram showed a right-bundle branch block. Coagulation abnormalities (PT 73.1%, APTT 39.4 s, FDP 235mg/dl) were observed 72 h before onset. Echocardiography revealed a large thrombus in a right ventricle. A diagnosis of pulmonary thromboembolism (PTE) was made, and a tissue-type plasminogen activator (monteplase) was administered under percutaneous cardiopulmonary support (PCPS). The complete lysis of thrombus was confirmed by an echocardiogram 8 h later. Symptoms and ABG data were also improved. PTE in adult AML cases is rare, but should be considered as one of the life-threatening complications in AML patients under chemotherapy who develop respiratory difficulties. We suggest a careful monitoring of coagulation abnormalities for the prediction of PTE during chemotherapy for AML, and the use of tissue-type plasminogen activator (t-PA), monteplase, for the treatment of PTE in these cases.
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PMID:A Case of Minimally Differentiated Acute Leukemia (AML-M0) Complicated by Ventricle Thrombosis During Remission-induction. 2740 95