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https://www.readbyqxmd.com/read/28814163/protease-activated-nanomaterials-for-targeted-cancer-theranostics
#1
Yung-Chieh Chan, Michael Hsiao
Cancer metastasis accompanies irreversible proteolysis. Malignant cells that abnormally express extracellular proteases usually lead to a poor outcome during cancer progression. The development of protease-activated drugs is an important goal. Moreover, the specific proteolytic mechanism can be used as a diagnostic strategy. Currently, nanotechnology for use in medication has been extensively developed to exploit the physical and chemical properties of nanoparticles. For example, to improve the efficacy of cancer therapy drugs, targeted delivery has been attempted by combining a targeting ligand with a nanoparticle...
August 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#2
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28812992/endolysosomal-degradation-of-allergenic-ole-e-1-like-proteins-analysis-of-proteolytic-cleavage-sites-revealing-t-cell-epitope-containing-peptides
#3
Sabrina Wildner, Brigitta Elsässer, Teresa Stemeseder, Peter Briza, Wai Tuck Soh, Mayte Villalba, Jonas Lidholm, Hans Brandstetter, Gabriele Gadermaier
Knowledge of the susceptibility of proteins to endolysosomal proteases provides valuable information on immunogenicity. Though Ole e 1-like proteins are considered relevant allergens, little is known about their immunogenic properties and T cell epitopes. Thus, six representative molecules, i.e., Ole e 1, Fra e 1, Sal k 5, Che a 1, Phl p 11 and Pla l 1, were investigated. Endolysosomal degradation and peptide generation were simulated using microsomal fractions of JAWS II dendritic cells. Kinetics and peptide patterns were evaluated by gel electrophoresis and mass spectrometry...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28808203/clinical-application-of-simultaneous-detection-of-cystatin-c-cathepsin-s-and-il-1-in-classification-of-coronary-artery-disease
#4
Ling Yan, Shuang Ding, Bing Gu, Ping Ma
Cystatin C, cathepsin S, and IL-1 are three important biomarkers of atherosclerosis. Previous studies emphasized the relationship between individual biomarkers in coronary artery disease (CAD) patients and severity of atherosclerostic lesions of the coronary arteries, while combined cystatin C, cathepsin S, and IL-1 have not been reported for clinical classification of CAD. We aimed to establish a link between cystatin C, cathepsin S, IL-1 and CAD in this cohort study. Totally 112 subjects were enrolled and divided into the stable angina pectoris group, the unstable angina pectoris group and the acute myocardial infarction (AMI) groups, and 50 healthy adults served as controls...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28802408/down-regulation-of-malate-synthase-in-mycobacterium-tuberculosis-h37ra-leads-to-reduced-stress-tolerance-persistence-and-survival-in-macrophages
#5
Kumar Sachin Singh, Rishabh Sharma, Deepa Keshari, Nirbhay Singh, Sudheer Kumar Singh
Malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide TCA cycle intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by down-regulating GlcB. The survival studies suggested increased susceptibility to oxidative and nitrosative stress as well as to rifampicin...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802000/pmepa1-induced-by-rankl-p38-mapk-pathway-has-a-novel-role-in-osteoclastogenesis
#6
Noboru Funakubo, Xianghe Xu, Toshio Kukita, Seiji Nakamura, Hiroshi Miyamoto, Akiko Kukita
Osteoclasts are multinucleated cells formed by fusion of preosteoclasts (POCs) derived from cells of the monocyte/macrophage lineage. We have reported a culture system that supports the formation of POCs from stroma-depleted rat bone marrow cells. Global gene expression analysis of this culture system identified genes highly expressed in POCs. Here, we have analyzed the expression and function of one of these highly expressed genes, prostate transmembrane protein androgen induced 1 (Pmepa1), a target of TGF-β and binds Nedd4 ubiquitin ligase, which plays a role in intracellular trafficking...
August 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28800445/enzyme-sensitive-gemcitabine-conjugated-albumin-nanoparticles-as-a-versatile-theranostic-nanoplatform-for-pancreatic-cancer-treatment
#7
Haijie Han, Jinhui Wang, Tingting Chen, Lichen Yin, Qiao Jin, Jian Ji
Development of gemcitabine (GEM) nanocarriers as theranostic agents for pancreatic cancer chemotherapy has received extensive attention in recent years. A novel enzyme-sensitive albumin-based GEM delivery nanoplatform was developed in this research by simple conjugation of GEM to human serum albumin (HSA) via cathepsin B cleavable peptide GFLG and then complexing with near-infrared (NIR) dye IR780, forming a HSA-GEM/IR780 complex. The successful preparation of HSA-GEM/IR780 complex was confirmed by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS), UV-vis-NIR absorption spectra and fluorescent emission spectra...
July 17, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28800383/epithelial-desquamation-observed-in-a-phase-i-study-of-an-oral-cathepsin-c-inhibitor-gsk2793660
#8
Bruce E Miller, Ruth J Mayer, Navin Goyal, Joanne Bal, Nigel Dallow, Malcolm Boyce, Donald Carpenter, Alison Churchill, Teresa Heslop, Aili L Lazaar
AIMS: Cathepsin C (CTSC) is necessary for the activation of several serine proteases including neutrophil elastase (NE), cathepsin G, and proteinase 3. GSK2793660 is an oral, irreversible inhibitor of CTSC that is hypothesized to provide an alternative route to achieve NE inhibition and was tested in a Phase I study. METHODS: Single escalating oral doses of GSK2793660 0.5 mg to 20 mg or placebo were administered in a randomized crossover design to healthy male subjects; a separate cohort received once daily doses of 12 mg or placebo for 21 days...
August 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28797985/the-role-and-mechanism-of-cathepsin-g-in-dermatomyositis
#9
Siming Gao, Honglin Zhu, Huan Yang, Huali Zhang, Qiuxiang Li, Hui Luo
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by CD4+ T cells and B cells infiltration in perivascular and muscle tissue. Although the infiltration of inflammatory cells plays a key role in muscle damage, the exact mechanism is not clear. Cathepsin G (CTSG) is a member of the serine proteases family and can increase the permeability of vascular endothelial cells and the chemotaxis of inflammatory cells. In this study, we found that the expression of CTSG was increased in peripheral blood mononuclear cells and muscle tissues of DM patients...
August 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28797057/a%C3%AE-42-mediated-proteasome-inhibition-and-associated-tau-pathology-in-hippocampus-are-governed-by-a-lysosomal-response-involving-cathepsin-b-evidence-for-protective-crosstalk-between-protein-clearance-pathways
#10
Karen L G Farizatto, Uzoma S Ikonne, Michael F Almeida, Merari F R Ferrari, Ben A Bahr
Impaired protein clearance likely increases the risk of protein accumulation disorders including Alzheimer's disease (AD). Protein degradation through the proteasome pathway decreases with age and in AD brains, and the Aβ42 peptide has been shown to impair proteasome function in cultured cells and in a cell-free model. Here, Aβ42 was studied in brain tissue to measure changes in protein clearance pathways and related secondary pathology. Oligomerized Aβ42 (0.5-1.5 μM) reduced proteasome activity by 62% in hippocampal slice cultures over a 4-6-day period, corresponding with increased tau phosphorylation and reduced synaptophysin levels...
2017: PloS One
https://www.readbyqxmd.com/read/28796811/biphasic-ros-production-p53-and-bik-dictate-the-mode-of-cell-death-in-response-to-dna-damage-in-colon-cancer-cells
#11
Ozgur Kutuk, Nurgul Aytan, Bahriye Karakas, Asli Giray Kurt, Ufuk Acikbas, Sehime Gulsun Temel, Huveyda Basaga
Necrosis, apoptosis and autophagic cell death are the main cell death pathways in multicellular organisms, all with distinct and overlapping cellular and biochemical features. DNA damage may trigger different types of cell death in cancer cells but the molecular events governing the mode of cell death remain elusive. Here we showed that increased BH3-only protein BIK levels promoted cisplatin- and UV-induced mitochondrial apoptosis and biphasic ROS production in HCT-116 wild-type cells. Nonetheless, early single peak of ROS formation along with lysosomal membrane permeabilization and cathepsin activation regulated cisplatin- and UV-induced necrosis in p53-null HCT-116 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28795851/selective-induction-of-apoptosis-in-mcf7-cancer-cell-by-targeted-liposomes-functionalized-with-mannose-6-phosphate
#12
Cristina Minnelli, Laura Cianfruglia, Emiliano Laudadio, Roberta Galeazzi, Michela Pisani, Emanuela Crucianelli, Davide Bizzaro, Tatiana Armeni, Giovanna Mobbili
Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalization and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28793886/cathepsin-s-degraded-decorin-are-elevated-in-fibrotic-lung-disorders-development-and-biological-validation-of-a-new-serum-biomarker
#13
S N Kehlet, C L Bager, N Willumsen, B Dasgupta, C Brodmerkel, M Curran, S Brix, D J Leeming, M A Karsdal
BACKGROUND: Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue homeostasis contributing to extracellular matrix remodeling diseases. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific fragment of degraded decorin, which has potential as a novel non-invasive serum biomarker for fibrotic lung disorders...
August 9, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28791438/vps52-induces-apoptosis-via-cathepsin-d-in-gastric-cancer
#14
Jian Zhang, Ying Lin, Xichun Hu, Zheng Wu, Weijian Guo
Vacuolar protein sorting (VPS) genes encode a class of proteins involved in vesicular trafficking. Growing evidence suggests that VPS proteins play roles in tumor biology. Vacuolar protein sorting 52 (VPS52) is involved in retrograde transport of endosomes, and its roles in cancers have not been explored. This study investigated the genetic alterations, protein changes, biological role, and molecular mechanism of VPS52 in gastric cancer. Loss of heterozygosity of VPS52 was detected in 52.9% (9/17) of gastric cancer samples...
August 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28791343/breast-cancer-associated-gene-3-interacts-with-rac1-and-augments-nf-%C3%AE%C2%BAb-signaling-in-vitro-but-has-no-effect-on-rankl-induced-bone-resorption-in-vivo
#15
Chen Yao, Kuan-Ping Yu, William Philbrick, Ben-Hua Sun, Christine Simpson, Changqing Zhang, Karl Insogna
Breast cancer-associated gene 3 (BCA3) is a recently identified adaptor protein whose functions are still being defined. BCA3 has been reported to be an important regulator of nuclear factor-κB (NF-κB) signaling. It has also been reported to interact with the small GTPase, Rac1. Consistent with that observation, in the present study, BCA3 was found to interact with nuclear Rac1 in 293 cells and influence NF-κB signaling. Additional experiments revealed that depending on cell type, BCA3 augmented, attenuated or had no effect on NF-κB signaling in vitro...
August 4, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28782357/beyond-a-carrier-graphene-quantum-dots-as-a-probe-for-programmatically-monitoring-anti-cancer-drug-delivery-release-and-response
#16
Hui Ding, Fan Zhang, Chaochao Zhao, Yanlin Lv, Guanghui Ma, Wei Wei, Zhiyuan Tian
On the basis of the unique physicochemical properties of graphene quantum dots (GQDs), we developed a novel type of theranostic agent by loading anticancer drug doxorubicin (DOX) to GQD's surface and conjugating Cy5.5 (Cy) dye to GQD though a cathepsin D-responsive (P) peptide. Such type of agents demonstrated superior therapeutic performance both in vitro and in vivo because of the improved tissue penetration and cellular uptake. More importantly, they are capable of functioning as probes for programmed tracking the delivery and release of anticancer drug as well as drug-induced cancer cell apoptosis through GQD's, DOX's, and Cy's charateristic fluorescence, respectively...
August 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28779890/effect-of-conditioning-solutions-containing-ferric-chloride-on-dentin-bond-strength-and-collagen-degradation
#17
Raquel Viana Rodrigues, Marcelo Giannini, Fernanda Miori Pascon, Preety Panwar, Dieter Brömme, Adriana Pigozzo Manso, Ricardo Marins Carvalho
OBJECTIVE: To investigate the effects of conditioning solutions containing ferric chloride (FeCl3) on resin-dentin bond strength; on protection of dentin collagen against enzymatic degradation and on cathepsin-K (CT-K) activity. METHODS: Conditioning solutions were prepared combining citric acid (CA) and anhydrous ferric chloride (FeCl3) in different concentrations. The solutions were applied to etch flat dentin surfaces followed by bonding with adhesive resin. Phosphoric acid (PA) gel etchant was used as control...
August 2, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28772283/the-interplay-of-matrix-metalloproteinase-8-transforming-growth-factor-%C3%AE-1-and-vascular-endothelial-growth-factor-c-cooperatively-contributes-to-the-aggressiveness-of-oral-tongue-squamous-cell-carcinoma
#18
Pirjo Åström, Krista Juurikka, Elin S Hadler-Olsen, Gunbjørg Svineng, Nilva K Cervigne, Ricardo D Coletta, Juha Risteli, Joonas H Kauppila, Sini Skarp, Samuel Kuttner, Ana Oteiza, Meeri Sutinen, Tuula Salo
BACKGROUND: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC). METHODS: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples...
August 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28771551/computational-investigation-of-conformational-variability-and-allostery-in-cathepsin-k-and-other-related-peptidases
#19
Marko Novinec
Allosteric targeting is progressively gaining ground as a strategy in drug design. Its success, however, depends on our knowledge of the investigated system. In the case of the papain-like cysteine peptidase cathepsin K, a major obstacle in our understanding of allostery is represented by the lack of observable conformational change at the active site. This makes it difficult to understand how binding of effectors at known allosteric sites translates into modified enzyme activity. Herein, we address this issue by a computational approach based on experimental data...
2017: PloS One
https://www.readbyqxmd.com/read/28771332/cathepsin-mediated-cleavage-of-peptides-from-peptide-amphiphiles-leads-to-enhanced-intracellular-peptide-accumulation
#20
Handan Acar, Ravand Samaeekia, Matthew R Schnorenberg, Dibyendu K Sasmal, Jun Huang, Matthew V Tirrell, James L LaBelle
Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein-protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide Amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation and PA monomers are internalized via endocytosis...
August 3, 2017: Bioconjugate Chemistry
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