Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell lines derived from human squamous cell (EPCL), large cell (LCLC), and small cell lung cancer (SCLC) lines were investigated for the expression of cathepsin B (Cat B) and cysteine proteinase inhibitors (CPIs). The EPLC and LCLC lines expressed 5- to 50-fold more Cat B activity and contained more mature Cat B of M(r) 27-29 kDa (> 2.5 microg/mg total protein) than the SCLC lines (< 1.0 microg/mg total protein). The LPLC lines also secreted the highest amounts of Cat B precursor of M(r) about 46 kDa. Inhibitory activities against Cat B and papain were associated with high molecular mass (HMM) and low molecular mass (LMM) inhibitory proteins, both in cell extracts and in media. About 75% of the inhibitory activity was associated with HMM inhibitors, the majority of which were kininogens (M(r) > or = 67 kDa). The LMM inhibitors of M(r) 10-15 kDa were cystatin C and stefins A and B, which were quantitated by ELISA: stefins A and B were present in cell extracts and medium in similar concentrations (5-200 ng/10(6) cells), while 80-99% of the cystatin C was released in the medium (10-195 ng/10(6) cells). Phorbol ester (PMA), which induces protein-kinase C mediated signal transduction and enhances cellular differentiation in many non-small cell lung cancer (NSCLC) cell lines, increased intracellular Cat B activity and Cat B protein as well as its secretion in some cell lines but not in others, regardless of their histological type. PMA significantly (P < 0.049) decreased intracellular stefin A concentrations in two EPLC lines and non-significantly in two LCLC lines. PMA decreased secretion of stefin A in all EPLC lines, but not in LCLC lines, while IGF-I significantly increased stefin B secretion in both SCLC lines. These data showed that lung tumor cells produce both cysteine proteinases and cystatins. As the antagonistic molecules are regulated differently in histologically different types of lung tumor cells, it is possible that an imbalance between the proteinases and their specific inhibitors plays a role in progression of certain types of lung tumors in vivo.
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PMID:Cathepsin B and cysteine proteinase inhibitors in human lung cancer cell lines. 921 25

It is well known that intensified insulin treatment of poorly controlled type 1 diabetic patients may worsen an existing diabetic retinopathy (DR). This observation has been explained by an insulin-induced stimulation of the GH/IGF-I axis. Here, we report on three cases, where the progression of DR during intensified metabolic control was treated with manipulation of insulin therapy and/or by administration of octreotide. Serum concentrations of IGF-I, IGFBP-3, insulin, cystatin C, creatinine, endogenous creatinine clearance and HbA1c-levels were assessed by routine laboratory methods; serum IGF-I bioactivity was estimated by a highly specific kinase receptor activation assay. Visual acuity and retinopathy stage was assessed by established clinical methods including fluorescein angiography. After glycaemic control was improved by intensified insulin therapy, serum IGF-I levels acutely increased. Subsequently, DR progressed to an advanced stage ("florid retinopathy"), with macular edema, and proliferation of new vessels (in two cases). Immediate reduction of insulin dosage and administration of octreotide lowered serum total IGF-I levels (and IGF-I bioactivity as measured in one patient). Subsequently, macular edema resolved partly, and visual acuity improved, allowing laser photocoagulation to be performed. In conclusion, in poorly controlled type 1 diabetic patients, intensified insulin therapy is able to cause florid DR with acute macular edema. These sight-threatening changes may improve by short-term reduction of insulin dosage or by administration of octreotide, and we speculate that this may be related to down-regulation of (serum) IGF-I.
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PMID:Progression of diabetic retinopathy during improved metabolic control may be treated with reduced insulin dosage and/or somatostatin analogue administration -- a case report. 1580 16

NS0 cells proliferate without external supply of growth factors in protein-free media. We hypothesize that the cells produce their own factors to support proliferation. Understanding the mechanisms behind this autocrine regulation of proliferation may open for the novel approaches to improve animal cell processes. The following proteins were identified in NS0 conditioned medium (CM): cyclophilin A, cyclophilin B (CypB), cystatin C, D-dopachrome tautomerase, IL-25, isopentenyl-diphosphate delta-isomerase, macrophage migration inhibitory factor (MIF), beta(2)-microglobulin, Niemann pick type C2, secretory leukocyte protease inhibitor, thioredoxin-1, TNF-alpha, tumour protein translationally controlled 1 and ubiquitin. Further, cDNA microarray analysis indicated that the genes for IL-11, TNF receptor 6, TGF-beta receptor 1 and the IFN-gamma receptor were transcribed. CypB, IFN-alpha/beta/gamma, IL-11, IL-25, MIF, TGF-beta and TNF-alpha as well as the known growth factors EGF, IGF-I/II, IL-6, leukaemia inhibitory factor and oncostatin M (OSM) were excluded as involved in autocrine regulation of NS0 cell proliferation. The receptors for TGF-beta, IGF and OSM are however present in NS0 cell membranes since TGF-beta(1) caused cell death, and IGF-I/II and OSM improved cell growth. Even though no ligand was found, the receptor subunit gp130, active in signal transduction of the IL-6 like proteins, was shown to be essential for NS0 cells as demonstrated by siRNA gene silencing.
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PMID:Proliferation of NS0 cells in protein-free medium: the role of cell-derived proteins, known growth factors and cellular receptors. 1943 15