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)

Lysozyme, alpha-amylase, neutral proteinase and plasminogen activator were most concentrated in the initial portion of the ejaculate that consists mostly of Cowper's gland and prostate gland fluids as well as spermatozoa. The concentration of the high molecular weight proteinase inhibitors, alpha1-antitrypsin and alpha1X-antichymotrypsin, was essentially unaltered throughout the ejaculate fractions, although their absolute amounts showed an increase towards the final fraction. By contrast, the total inhibitory activity towards pancreatic trypsin was highest both in concentration and amount in the last fraction, thus indicating that the seminal vesicles are its primary source. Plasminogen, prothrombin, Factor XIII, and the proteinase inhibitors antithrombin III, alpha2-macroglobulin, inter-alpha-trypsin inhibitor and C1S-inactivator could not be detected immunochemically in whole ejaculates, and indicates the dissimilarity between the coagulation/liquefaction processes of semen and blood.
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PMID:Components of human split ejaculates. II. Enzymes and proteinase inhibitors. 108 6

There is still an urgent need for improved treatments for metastatic cancer. Although the phospholipase A(2) (PLA(2)) crotoxin, an antitumor protein that appears to act by interaction with epidermal growth factor receptors (EGFR), has recently shown activity in breast cancer in phase I clinical trials, it also displayed nonspecific neurotoxicity. Therefore, the aim of this study was to apply a novel concept called polymer-masked-unmasked-protein therapy (PUMPT) to give a bioresponsive dextrin-PLA(2) conjugate that would reduce PLA(2) systemic toxicity but retain antitumor activity following alpha-amylase triggered degradation of dextrin in the tumor interstitium. Dextrin (M(w) approximately 60000 g/mol; approximately 22 mol % succinoylation) and PLA(2) (from honey bee venom) were chosen as models for these initial studies, and the conjugates synthesized contained 6.1 wt % PLA(2), with <1% free enzyme. The conjugate showed decreased ( approximately 36%) enzyme activity compared to native PLA(2), but activity was restored to approximately 100% following incubation with alpha-amylase. Whereas dextrin conjugation caused a marked reduction in PLA(2)'s hemolytic activity, the conjugate was cytotoxic toward MCF-7, HT29, and B16F10 cells at a level that was comparable to, or greater than, that seen for free PLA(2). In these cell lines, cytotoxicity showed partial correlation with the level of EGFR expression. The reduced toxicity and alpha-amylase triggered activity of the dextrin-PLA(2) conjugate confirmed the potential of this approach for further development as a novel anticancer treatment.
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PMID:Dextrin-phospholipase A2: synthesis and evaluation as a bioresponsive anticancer conjugate. 1935 76

The bioresponsive conjugate dextrin-phospholipase A2 (PLA2) is a novel anticancer polymer therapeutic. Dextrin conjugation decreases PLA2 bioactivity, but this can be restored following triggered degradation by alpha-amylase. The conjugate displays reduced hemolytic activity but retains, or shows enhanced, cytotoxicity in vitro that partially correlates with epidermal growth factor receptor (EGFR) expression. Here, we investigate further the mechanism of action of dextrin-PLA2 with the aim of judging its potential for combination with tyrosine kinase inhibitors (TKI) and/or chemotherapy and selecting the first models for in vivo evaluation. The endocytic fate of Oregon Green (OG)-labeled probes was assessed in MCF-7 cells. Whereas PLA2-OG showed greatest membrane binding, the dextrin-PLA2-OG conjugate displayed higher internalization. Moreover, cells incubated with PLA(2)-OG and dextrin-PLA2-OG showed an altered pattern of intracellular vesicle distribution compared to dextrin-OG. When cell lines known to express different levels of EGFR were used to assess cytotoxicity, free PLA2 activity was enhanced by addition of EGF whereas the conjugate was less cytotoxic, perhaps due to differences in their PK/PD profile. Co-incubation of cells with the TKI inhibitor, gefitinib, led to reduced cytotoxicity of both PLA2 and dextrin-PLA2 suggesting a TK-mediated PLA2 mechanism of action. However, the enhanced cytotoxicity seen in the presence of doxorubicin suggested potential for development of a dextrin-PLA2/doxorubicin combination therapy.
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PMID:Studies on the mechanism of action of dextrin-phospholipase A2 and its suitability for use in combination therapy. 2016 58