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

Cathepsins B, H and L have been shown to participate in processes of tumor growth, vascularization, invasion and metastasis. Their levels in tumor tissue extracts can provide useful clinical information to predict disease-free and overall survival in breast, lung, colorectal, brain and head and neck cancer patients. Recently we have found that both cysteine cathepsins and their endogenous protein inhibitors stefins and cystatin C can also predict prognosis when measured extracellularly. In melanoma and colorectal cancer patients high serum levels of cathepsins B and H correlated with shorter survival. Similarly, increased extracellular levels of stefins A and B and cystatin C correlated significantly with high risk of adverse outcome in cancer patients. However, the cathepsin B/cystatin C complex was found to be less abundant in sera of patients with malignant tumors than in those with benign diseases or in healthy controls, suggesting an imbalance between the enzyme and its inhibitor in cancer patients.
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PMID:Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. 1076 47

Cystatin C is the best known extracellular endogenous cysteine proteinase inhibitor and has been studied as a possible index of tumor growth and as a marker of the effectiveness of antitumor therapy. The aim of this study was to evaluate cystatin C concentrations in murine tumor tissues (compared with other organs not directly involved with tumor development, such as the liver and spleen) during treatment with several antitumor drugs (Ukrain and/or cyclophosphane). Cystatin C concentrations in murine tissues and biological fluids was determined by enzyme-linked immunosorbent (ELISA) assay. The cystatin C ELISA test is a sandwich immunoassay, which uses immobilized rabbit antihuman cystatin C Pab and mouse antihuman cystatin C Mab-HRP (monoclonal antibodies, conjugated with horseradish peroxidase). We observed decreased serum cystatin C concentrations compared with controls in all nontreated tumor models: HA-1 hepatoma (solid and ascitic forms), lung adenocarcinoma (solid and ascitic forms) and LS lymphosarcoma. In the ascitic fluid of mice with HA-1 hepatoma the cystatin C concentration was much lower than in the serum of the same mice (about 20-fold lower). In the HA-1 model of hepatoma cells cystatin C concentration decreased about 2-3-fold compared with the control (intact liver) and Ukrain significantly increased the cystatin C concentration. Cyclophosphane treatment of LS lymphosarcoma significantly increased the cystatin C concentration in serum. Cyclophosphane treatment (50 mg/kg, single injection) increased cystatin C by up to 8-fold more in tumor issue. Ukrain treatment of LS lymphosarcoma was also followed by increased levels of cystatin C in tumor tissue (4-fold); cyclophosphane plus Ukrain had a similar positive effect. In the group with LS lymphosarcoma Ukrain or cyclophosphane plus Ukrain treatment induced a significant increase in cystatin C concentration in liver. Liver cystatin C concentration decreased in the HA-1 hepatoma group and treatment with Ukrain or carboxymethylated beta-1, 3-glucan (CMG) increased this index in both groups. Spleen cystatin C concentrations decreased about 5-fold in LS lymphosarcoma compared with controls and combined treatment with cyclophosphane plus Ukrain restored the index to the normal value. We can conclude that both murine tumors studied were characterized by low cystatin C concentrations in tumor tissues and decreased cystatin C concentrations (to a lesser degree) were also observed in liver and spleen as a result of the "toxic" effect of tumor bearing. Effective treatment in all cases (especially with Ukrain or a combination of cyclophosphane plus Ukrain) induced a significant increase in cystatin C. Obviously, the decrease in cystatin C concentration predominantly in tumor tissue was connected with tumor development and restoration of cystatin C level may be used as a marker of efficacy of antitumor therapy.
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PMID:Cysteine proteinase inhibitor level in tumor and normal tissues in control and cured mice. 1134 42

The growth of LS-lymphosarcoma in CBA mice was accompanied by a decrease in the content of the major extracellular inhibitor cystatin C in the tumor, plasma and, to a lesser extent, in tissues not involved in tumor process (liver and spleen). Cyclophosphamide in a dose of 50 mg/kg prolonged the life-span of animals and decreased tumor size by 80%. Cathepsin B and L activities in the tumor tissue increased by 3 and 7 times, respectively. Cystatin C content in the tumor tissue, spleen, and plasma also increased. Cystatin C assay in tumor tissue and plasma helps to predict the rate of tumor growth and to evaluate the efficiency of antitumor therapy.
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PMID:Role of cystatin C and cysteine proteinases in the development of mouse LS-lymphosarcoma. 1168 51

We measured plasma cystatin C concentration and activity of cathepsins B and L in tumor tissue as possible markers for the efficiency of antitumor therapy and prognostic criteria for Lewis lung adenocarcinoma in mice. Plasma cystatin C concentration markedly decreased in mice with tumors. During successive therapy the increase in plasma cystatin C concentration correlated with the degree of inhibition of tumor growth. Activities of cathepsins B and L in the liver increased in animals with tumors. In mice receiving successive antitumor therapy activities of cathepsins B and L increased in tumor tissue, but decreased in the liver (compared to untreated animals).
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PMID:Cystatin C and cysteine proteinases during the development and therapy of Lewis lung adenocarcinoma in mice. 1271 21

Cystatin C is a low-molecular endogenous inhibitor of cysteic proteinases. Sets for immune-enzyme assay of cystatin C in human blood serum (KRKK, Slovenia) were made used of in the case study. The concentration of cystatin C (CCC) in blood serum was found to be higher in cases of certain hemoblastoses (Non-Hodgkin's disease, lymphogranulomatosis and multiple myeloma), with the highest concentration of the inhibitor being observed in patients with resistance to the conducted polychemotherapy and a poor prognostication. The treatment of Non-Hodgkin's disease and of lymphogranulomatosis brought about a normalized CCC in blood serum. It was suggested that CCC in blood serum reflects a nature of tumor growth and, obviously, it can be a criterion in assessing the therapy efficiency. The concentration of alpha 1-proteinases inhibitor remained unchanged before and after treatment.
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PMID:[Immunoenzyme technique for analysis of cystatin C in serum of patients with hemoblastosis]. 1293 31

Development of murine HA-1 hepatoma was accompanied by increased activity of cathepsin B (in ascitic cells), cathepsin D (in ascitic fluid) and increased activity of procathepsin B. There were some changes of cysteine proteinases in liver and spleen, not involved directly into tumor growth. The most prominent changes included the decreased level of cysteine proteinase inhibitors cystatin C and stefin A in ascitic cells (and to a lesser degree in liver tissue). During tumor development serum cystatin C concentration decreased by 3-times compared to intact mice. Treatment by antitumor drug Ukraine increased life span of mice with HA-1 hepatoma (transplanted intravenously), decreased the increment of tumor weight. In ascite such treatment caused a decrease of number of tumor cells and an increase of number of macrophages. Ukraie (administered once or 5-times in a dose of 0.5 mg per mice) increased cystatin C level, revealing protective mechanism of action.
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PMID:[Cysteine proteinases and their inhibitors in the development of mouse HA-1 hepatoma and antineoplastic therapy]. 1517 24

Human cystatin C is a cysteine proteinase inhibitor with potential applications as an anti-viral agent, cancer tumor growth inhibitor, and in prevention of proteolysis during food processing. A glycosylated cystatin C mutant with increased temperature stability was developed for the latter application [Nakamura et al. (1998) FEBS Lett 427:252-254]. A recombinant variant of cystatin C [Nakamura et al. (2000) International patent no. PLTCA99/00717] with two potential sites for N-linked glycosylation was expressed in Pichia pastoris Mut(s). Little of the cystatin C produced was in the glycosylated form under fermentation conditions of pH 6, temperature 28 degrees C, methanol only feed, and ammonium hydroxide as a nitrogen source. Thus, the effect of addition of complex nitrogen sources, peptone and amino acid supplements, on the yield and glycosylation of this mutant cystatin C were investigated. A full factorial design experiment using 2-l fermenters was performed with three factors: ammonium hydroxide, peptone, and an amino acid mix, at two levels, absent or present. Peptone addition was found to have a positive, and the most significant, effect on cell specific cystatin C yield. A maximum mutant cystatin C yield of 0.82 mumol (g-dry cell weight)(-1) min(-1) was obtained when all three nitrogen sources were used together. However, under these conditions only 16% of protein was in the glycosylated form since ammonia was found to have a significant negative effect on glycosylation extent. The maximum extent of glycosylation was 30% when peptone and amino acid mix were the only nitrogen sources added.
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PMID:The effect of nitrogen source on yield and glycosylation of a human cystatin C mutant expressed in Pichia pastoris. 1566 45

Angiogenesis is the formation of new blood vessels out of the existing vascular bed. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent circulating angiogenic factors, whereas cystatin C is one of the most important extracellular inhibitors of several cysteine proteinases. Because proteases degrade interstitial connective tissue and basement membranes during tumor growth and metastasis, an association between cystatin C and the angiogenic factors seems plausible. The primary aim of the present study was to investigate if such a correlation exists between these serum markers. The secondary aim was to determine the prognostic value of these circulating cytokines and cystatin C, collected prior to therapy, in patients with esophageal carcinoma.A total of 42 patients with esophageal carcinoma donated serum samples prior to therapy. VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p = 0.04), whereas bFGF was not (p = 0.08). VEGF was significantly correlated with cystatin C (p = 0.027). Survival analysis showed that VEGF regarded as a continuous variable was associated with a significantly poorer survival in the univariate analysis (p = 0.023); however, this was not found for bFGF (p = 0.46). Neither of the angiogenic factors were associated with survival in the multivariate analysis. In the univariate analysis, cystatin c was correlated with survival (p = 0.01), but this was not found in the multivariate analysis (p = 0.28). In conclusion, VEGF was correlated with cystatin C, possible explanations being discussed in the present article. Results of the present study indicate that use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, appears limited.
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PMID:The role of cystatin C and the angiogenic cytokines VEGF and bFGF in patients with esophageal carcinoma. 1575 Jan 94

BACKGROUND: Tumor metastasis is a frequent cause of treatment failure for cancer patients. A key feature of metastatic cancer cells is their invasive ability. Cysteine proteases contribute to invasive properties of many cancer cell types. To analyze the contribution of cysteine proteases to metastasis we have over-expressed in B16 melanoma cells the natural cysteine protease inhibitor, cystatin C. We measured in vitro invasion of cystatin over-expression clones with Boyden chamber type assays. Tail-vein injections of cells were used to compare lung tumor colonization. Subcutaneous tumor growth and tumor cell metastasis from primary tumors were also analyzed. Apoptosis of tumor cells was measured in lung tissues following melanoma cell injection. RESULTS: Results show the in vitro invasion of cystatin C over-expressing cells was dramatically inhibited. Lung tumor colonization was also reduced. Increased tumor cell apoptosis was found to be an important factor and may be related to the reduced tumor burden noted in this system of melanoma metastasis. CONCLUSION: Cysteine proteases therefore, may be a target for future anti-metastatic therapies.
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PMID:Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression. 1590 19

Cystatins function as cysteine protease inhibitors, are expressed in numerous cell types, and regulate a number of physiological processes. Four cystatins have been extensively studied: cystatin A, cystatin B, cystatin C, and cystatin M. Aberrant regulation of cystatins occurs in a number of diseases, including cancer and certain neurodegenerative disorders. Recent advances in the understanding of cystatin function suggest that these proteins may regulate promotion or suppression of tumor growth, invasion, and metastasis. Cancer is a disease of abnormal gene expression and cancer cells exhibit aberrant epigenetic events (such as DNA methylation), leading to gene silencing. Cystatins are epigenetically silenced through DNA methylation-dependent mechanisms in several forms of cancer, including breast, pancreatic, brain, and lung. These findings suggest that DNA methylation-dependent epigenetic mechanisms may play an important role in the loss of cystatin gene expression and protein function during neoplastic transformation and/or tumor progression. This review summarizes the biological processes in which cystatins function, focuses on the neoplastic events that involve aberrant regulation of cystatins, and discusses the possible epigenetic regulation of cystatins in cancer.
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PMID:Epigenetic regulation of cystatins in cancer. 1927 77


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