Search results for "cathepsin"
showing 10 items of 170 documents
Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis
2019
CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aim…
Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates
2018
A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and ev…
Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth
2012
International audience; Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the relea…
Flow cytometric DNA analysis and lysosomal cathepsins B and L in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters an…
1995
Background. The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. Methods. Flow cytometric DNA ploidy and S‐phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC. Lysosomal cathepsin B and L activity levels were determined biochemically in match…
Cathepsin D, B and L circulating levels as prognostic markers of malignant progression
1996
Growing evidence indicates that lysosomal Cathepsins D (CD), B (CB) and L (CL) may promote carcinogenesis and tumor progression. Therefore, we evaluated their potential value as biochemical parameters of malignant progression in patients with benign diseases which may undergo malignant transformation, such as liver cirrhosis (LC) and chronic pancreatitis (CHP) as well as in hepatocellular carcinoma (HCC) and pancreatic cancer (DPC). CD, CB and CL serum levels were determined by immunoenzymatic assays in LC, CHP, HCC or DPC patients and correlated with a number of biochemical and clinical parameters of these diseases. CD serum levels were increased in LC, CHP and HCC, but not in the DPC grou…
Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors.
2000
In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strong…
Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implicati…
1997
The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as comp…
Cathepsin D serum mass concentrations in patients with hepatocellular carcinoma and/or liver cirrhosis
1996
Cathepsin D serum mass concentrations were determined by enzyme immunoassay in patients with hepatocellular carcinoma (n = 51) and/or liver cirrhosis (n = 92) or benign steatosis (n = 16) and correlated with some biochemical and clinical properties of these diseases. Increased cathepsin D serum mass concentrations (P < 0.001) were observed in all these groups of patients as compared to normal subjects (n = 98). However, patients with steatosis had serum mass concentrations of this enzyme significantly lower (mean 2—3 fold) than those measured in cancer patients (P < 0.05) or cirrhotic patients (P < 0.001). Interestingly, significantly higher cathepsin D serum mass concentrations (m…
Antibodies to Cathepsin G in Crohn's disease
1992
. Antibodies directed against antigens in human neutrophils have proved to be of great diagnostic value in certain systemic vasculitides. Recent reports have focused the attention on these antigens as targets of antibodies in sera of patients with inflammatory bowel disease. We investigated the sera drawn from 60 patients suffering from biopsy proven Crohn's disease and 15 patients with active ulcerative colitis. Using sensitive enzyme-linked immunosorbent assays with purified antigens and Western blotting the following antibodies could be demonstrated: cathepsin G (cat-G) antibodies IgG 38.3%, IgM 13.3%, IgA 23.3% and antibodies against human leucocyte elastase (HLE) IgG, IgA, IgM 3.3%. Lo…
Expression of cysteine proteinases cathepsins B and K and of cysteine proteinase inhibitor cystatin C in giant cell tumor of tendon sheath.
2001
The expression of cysteine proteinases cathepsins B and K and of the endogenous inhibitor of cysteine proteinases, cystatin C, was investigated in tissue specimens of patients with giant cell tumor of tendon sheath (GCTTS). Expression of both enzymes was examined by immunohistochemistry in tissue specimens of 14 patients with GCTTS. Applying double-labeling techniques, the coexpression of cathepsin B and its major endogenous inhibitor cystatin C was additionally studied. Cells expressing the respective proteins were further characterized with the macrophage markers HAM56 and anti-CD68 (clone PG-M1). Cathepsin B could be detected in numerous HAM56-positive mononuclear cells (MC), but only in…