Search results for "Epsin"
showing 10 items of 218 documents
Bioinspired self-assembly of tyrosinase-modified silicatein and fluorescent core-shell silica spheres.
2014
Inspired by the intermolecular cross-linking of mussel foot proteins and their adhesive properties, tyrosinase has been used to modify recombinant silicatein. DOPA/DOPAquinone-mediated cross-linking and interfacial interactions enhanced both self-assembly of silicatein building blocks and templating of core–shell silica spheres, resulting in fluorescent biomimetic silicatein–silica hybrid mesofibers.
Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate.
2007
Phosphatidylinositol 4,5-bisphosphate [PI(4,5) P 2 ], a phosphoinositide concentrated predominantly in the plasma membrane, binds endocytic clathrin adaptors, many of their accessory factors, and a variety of actin-regulatory proteins. Here we have used fluorescent fusion proteins and total internal reflection fluorescence microscopy to investigate the effect of acute PI(4,5) P 2 breakdown on the dynamics of endocytic clathrin-coated pit components and of the actin regulatory complex, Arp2/3. PI(4,5) P 2 breakdown was achieved by the inducible recruitment to the plasma membrane of an inositol 5-phosphatase module through the rapamycin/FRB/FKBP system or by treatment with ionomycin. PI(4,5)…
Cathepsin D in the malignant progression of neoplastic diseases
1992
Recent studies suggest that aspartic proteinase Cathepsin D may be implicated in the process of tumor invasion and metastasis. In fact several in vitro observations showed that this proteinase may facilitate the spread of neoplastic cells through different mechanisms related to its proteolytic activity by acting at different levels of the metastatic cascade. Cathepsin D may promote tumor cell proliferation by acting as an autocrine mitogen through the activation of latent forms of growth factors or by interacting with growth factor receptors. The enzyme was also shown to be able to degrade in vitro extracellular matrix and to activate latent precursors forms of other proteinases involved in…
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…
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
2020
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attr…
Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings…
2016
The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluo…
Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors
2016
Novel rhodesain inhibitors were developed by combining an enantiomerically pure 3-bromoisoxazoline warhead with a 1,4-benzodiazepine scaffold as specific recognition moiety. All compounds were proven to inhibit rhodesain with Ki values in the low-micromolar range. Their activity towards rhodesain was found to be coupled to an in vitro antitrypanosomal activity, with IC50 values ranging from the mid-micromolar to a low-micromolar value for the most active rhodesain inhibitor (R,S,S)-3. All compounds showed a good selectivity against the target enzyme since all of them were proven to be poor inhibitors of human cathepsin L. Novel rhodesain inhibitors were developed by combining an enantiomeri…
Multicentric randomised study ofHelicobacter pylorieradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study
2017
IntroductionPopulation-based eradication ofHelicobacter pylorihas been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whetherH pylorieradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluat…
Cathepsin-B Induced Controlled Release from Peptide-Capped Mesoporous Silica Nanoparticles
2014
New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin B expressing cells are described. Nanometric mesoporous MCM-41 supports loaded with safranin O (S1-P) or doxorubicin (S2-P) containing a molecular gate based on a cathepsin B target peptidic sequence were synthesized. Solids were designed to show "zero delivery" and to display cargo release in the presence of cathepsin B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsin B cell lines were also tested. Release of safranin O and doxorubicin in these cells took place when cathepsin B was active or presen…
Non-Invasive Diagnosis of Gastroesophageal Reflux Disease Using Gastrin- and Pepsinogen-Based Tests
2018
Abstract Gastrin-17 (G-17), pepsinogen-1 (Pg1) and pepsinogen-2 (Pg2) reflect the functional state of gastric mucosa and are used for non-invasive diagnosis and screening of atrophic gastritis. The aim of the study was to clarify if erosive reflux disease (ERD) or non-ERD (NERD) can be distinguished from other dyspeptic conditions in patients, in a non-invasive manner using specific biomarkers. Levels of G-17, Pg1, and Pg2 were measured in 141 ERD patients (median age 48 years, males — 68), 122 NERD patients (median age 45 years, males — 32) and 410 control patients (median age 50 years, males — 97). Levels of biomarkers in ERD and NERD groups were compared to controls. Median levels of G-1…