Search results for "Cathepsin K"

showing 10 items of 17 documents

Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions

2016

Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients. Osteoclast activity was evaluated by tartrate resistant acid phosphatase (TRAP) staining and …

0301 basic medicinePyridines -- pharmacologyPyridinesPyridineImmunoenzyme TechniqueOsteoclastsApoptosisRANK Ligand -- genetics -- metabolismImmunoenzyme Techniqueschemistry.chemical_compoundBone Resorption -- drug therapy -- metabolism -- pathology0302 clinical medicineOsteogenesisCathepsin KMedicineAnilidesAnilides -- pharmacologyOsteoprotegerin -- genetics -- metabolismOsteoclasts -- cytology -- drug effects -- physiologyHuman primary cellCells CulturedTartrate-resistant acid phosphataseReceptor Activator of Nuclear Factor-kappa B -- genetics -- metabolismbiologyProto-Oncogene Proteins c-met -- genetics -- metabolismReceptor Activator of Nuclear Factor-kappa BReverse Transcriptase Polymerase Chain ReactionOsteoblastOsteogenesiOsteoblastCell DifferentiationSciences bio-médicales et agricolesProto-Oncogene Proteins c-metOsteoblasts -- cytology -- drug effects -- physiologymedicine.anatomical_structureCell Differentiation -- drug effectsOncologyRANKL030220 oncology & carcinogenesishuman primary cellsOsteoclastosteoprotegerin (OPG)bone microenvironmentHumanResearch Papermusculoskeletal diseasesmedicine.medical_specialtyCabozantinibBlotting WesternOsteogenesis -- drug effects -- physiologyReal-Time Polymerase Chain ReactionBone resorption03 medical and health sciencesOsteoprotegerinOsteoclastcabozantinibInternal medicineHumansRNA MessengerBone ResorptionCell ProliferationOsteoblastsbusiness.industryRANK LigandAnilideOsteoprotegerinApoptosiBone microenvironment; Cabozantinib; Human primary cells; Osteoprotegerin (OPG); Receptor activator of nuclear factor-kb ligand (RANKL); Anilides; Apoptosis; Blotting Western; Bone Resorption; Cell Differentiation; Cell Proliferation; Cells Cultured; Humans; Immunoenzyme Techniques; Osteoblasts; Osteoclasts; Osteogenesis; Osteoprotegerin; Proto-Oncogene Proteins c-met; Pyridines; RANK Ligand; RNA Messenger; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Oncology030104 developmental biologyEndocrinologychemistrybiology.proteinbusinessRNA Messenger -- geneticsreceptor activator of nuclear factor-kb ligand (RANKL)
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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…

AdultMaleCathepsin KAntigens Differentiation MyelomonocyticCathepsin ECell CountCathepsin FBiologyCysteine Proteinase InhibitorsGiant CellsCathepsin BPathology and Forensic MedicineCathepsin CCathepsin BImmunoenzyme TechniquesTendonsCathepsin OCathepsin HAntigens CDCathepsin L1HumansCystatin CCathepsin SAgedMuscle NeoplasmsGiant Cell TumorsAntibodies MonoclonalMiddle AgedMolecular biologyCathepsinsCystatinsBiochemistryLeukocytes MononuclearFemaleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

2001

Cholesteatoma is a nonneoplastic lesion of the middle ear space or mastoid that is histologically characterized by a progressive bone erosion of the ossicles and surrounding bone. Several matrix-degrading enzymes have been implicated as mediators of this bone erosion. Because the novel cysteine proteinase cathepsin K has been shown to play a central role in bone resorption, we examined the expression of this enzyme in tissue specimens of cholesteatoma. Tissue specimens of 9 patients with cholesteatoma were obtained during middle-ear surgery. Expression of cathepsin K mRNA was determined by RT-PCR using specific primers. Immunohistochemical analysis of cathepsin K protein expression in tissu…

AdultMalePathologymedicine.medical_specialtyCathepsin KOsteoclastsMatrix (biology)Giant CellsBone resorptionPathology and Forensic MedicineImmunoenzyme Techniquesotorhinolaryngologic diseasesCathepsin KmedicineHumansRNA MessengerBone ResorptionChildAgedCathepsin SCathepsinCholesteatoma Middle EarReverse Transcriptase Polymerase Chain ReactionChemistryCholesteatomaMiddle Agedmedicine.diseaseCathepsinsEpitheliummedicine.anatomical_structureGiant cellFemaleModern Pathology
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The effect of surgical suture material on osteoclast generation and implant-loosening

2020

Background: Implant loosening - either infectious or aseptic- is a still a major complication in the field of orthopaedic surgery. In both cases, a pro-inflammatory peri-prosthetic environment is generated by the immune system - either triggered by bacteria or by implant wear particles - which leads to osteoclast differentiation and osteolysis. Since infectious cases in particular often require multiple revision surgeries, we wondered whether commonly used surgical suture material may also activate the immune system and thus contribute to loss of bone substance by generation of osteoclasts. Methods: Tissue samples from patients suffering from infectious implant loosening were collected intr…

AdultMalePathologymedicine.medical_specialtyProsthesis-Related InfectionsOsteolysisimplant-associated infectionOsteoclasts03 medical and health sciences0302 clinical medicineSuture (anatomy)OsteoclastmedicineCathepsin KHumansOrthopedic ProceduresAgedAged 80 and overSuturesbusiness.industryInterleukin-8Cell DifferentiationProstheses and ImplantsGeneral MedicineMiddle Agedmedicine.diseasesurgical suture materialProsthesis FailureResorptionSurgical suturemedicine.anatomical_structureGiant cellOsteoclastFemale030211 gastroenterology & hepatologyImplantosteolysisbusinessResearch PaperInternational Journal of Medical Sciences
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Cathepsin L in metastatic bone disease: therapeutic implications

2010

AbstractCathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests that this endopeptidase might also be implicated in the regulation of other important biological functions, including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodeling processes, could contribute to facilitate bone metastasis formation. In support of this hypothesis, recent studies indicate that cathepsin L can foster this process by triggering multiple mechanisms which, in part, differ from those of t…

Bone diseaseClinical BiochemistryBone NeoplasmsBone metastasis; cancer; cathepsin K; cathepsin L; cysteine proteinases; proteinase inhibitorsBiologycathepsin KBiochemistryBone and BonesBone resorptioncathepsin LBone remodelingcysteine proteinaseCathepsin LmedicineCathepsin KAnimalsHumanscancerNeoplasm MetastasisMolecular BiologyCathepsinProteolytic enzymesproteinase inhibitorsBone metastasismedicine.diseaseBone metastasiCancer researchbiology.proteinSettore BIO/14 - Farmacologia
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miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone di…

2013

Skeletal homeostasis relies upon a fine tuning of osteoclast (OCLs)-mediated bone resorption and osteoblast (OBLs)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease. Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells,…

Bone diseasePhysiologyCellular differentiationCathepsin KClinical BiochemistryGene ExpressionOsteoclastsOsteolysisMMP9Cathepsin KCells CulturedTartrate-resistant acid phosphataseTumorCulturedReceptor Activator of Nuclear Factor-kappa BGenes fosCell DifferentiationOsteoblastCell biologyIsoenzymesmultiple myelomamedicine.anatomical_structureMatrix Metalloproteinase 9osteoclastMatrix Metalloproteinase 2medicine.medical_specialtyfosCellsAcid PhosphataseBiologyCollagen Type IBone resorptionCell LineOsteoclastCell Line TumorInternal medicinemedicineHumansBone ResorptionOsteoblastsmicroRNA.NFATC Transcription FactorsTartrate-Resistant Acid PhosphatasemiR-29bCell Biologymedicine.diseaseActinsMicroRNAsEndocrinologyGenesAcid Phosphatase; Actins; Bone Resorption; Cathepsin K; Cell Differentiation; Cell Line Tumor; Cells Cultured; Collagen Type I; Gene Expression; Genes fos; Humans; Isoenzymes; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; MicroRNAs; Multiple Myeloma; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Osteolysis; Receptor Activator of Nuclear Factor-kappa BJournal of Cellular Physiology
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Circulating cathepsin K and cystatin C in patients with cancer related bone disease: clinical and therapeutic implications.

2007

Abstract The clinical significance of serum cathepsin K and cystatin C was assessed in patients with breast cancer (BCa) or prostate cancer (PCa) with confined disease (M0) or bone metastasis (BM). Cathepsin K and cystatin C circulating levels were determined by ELISAs in 63 cancer patients, in 35 patients with nonmalignant diseases and in 42 healthy blood donors (control group). In BCa patients, cathepsin K serum levels were significantly lower than in sex matched control group (HS; p  = 0.0008) or in patients with primary osteoporosis (OP; p  = 0.0009). On the contrary, cystatin C levels were significantly higher in BCa patients than in HS ( p  = 0.0001) or OP ( p  = 0.017). In PCa patien…

CA15-3Malemedicine.medical_specialtyCathepsin KProstatic HyperplasiaBone NeoplasmsBreast NeoplasmsEnzyme-Linked Immunosorbent Assayurologic and male genital diseasesZoledronic AcidProstate cancerInternal medicinemedicineCathepsin KBiomarkers TumorHumansCystatin CAgedPharmacologyAged 80 and overbiologyBone Density Conservation AgentsDiphosphonatesbusiness.industryBone cancerImidazolesCancerBone metastasisProstatic NeoplasmsGeneral MedicineMiddle Agedmedicine.diseaseCathepsinsCystatinsBone metastasis; cathepsin K; Cystatin CEndocrinologyZoledronic acidCystatin CROC CurveBone metastasiCase-Control Studiesbiology.proteinDisease ProgressionOsteoporosisFemaleDrug Monitoringbusinessmedicine.drugBiomedicinepharmacotherapy = Biomedecinepharmacotherapie
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Collagenolytic proteinases in keratoconus.

2006

To study the proteolytic phenomena contributing to the pathogenesis of keratoconus, corneal enzymes with potential to cleave fibrillar collagen were studied.Immunohistochemical labeling was undertaken of conventional and novel mammalian collagenases (MMP-1, -2, -8, -13, and -14) of the matrix metalloproteinase (MMP) family and other collagenolytic proteinases of the serine (human trypsin-2) and cysteine (cathepsin K) endoproteinase families. The results were analyzed using a semiquantitative scoring system.Labeling of MMP-8 was moderate in healthy controls, but weak in keratoconus. Moderate MMP-2 and weak MMP-14 expressions were similar in controls and keratoconus. MMP-1 was slightly overex…

KeratoconusPathologymedicine.medical_specialtygenetic structuresCathepsin KMatrix metalloproteinaseKeratoconusPathogenesisCorneaImmunoenzyme TechniquesCorneamedicineCathepsin KHumansTrypsinCollagenaseschemistry.chemical_classificationmedicine.diseaseCathepsinseye diseasesMatrix MetalloproteinasesOphthalmologyEnzymemedicine.anatomical_structurechemistryCollagenaseTrypsinogenImmunohistochemistrysense organsKeratoplasty Penetratingmedicine.drugCornea
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Osteoclast-like Giant Cell Tumor of the Pancreas With Ductal Adenocarcinoma: Case Report with Novel Data on Histogenesis

2002

MalePathologymedicine.medical_specialtyPancreatic diseaseEndocrinology Diabetes and MetabolismCathepsin KOsteoclastsBiologyHistogenesisCathepsin BEndocrinologyImmunophenotypingOsteoclastInternal MedicinemedicineHumansPancreatic ductHepatologyGiant Cell TumorsOsteoclast-Like Giant CellMiddle Agedmedicine.diseaseCathepsinsImmunohistochemistryPancreatic Neoplasmsmedicine.anatomical_structureAdenocarcinomaPancreasCarcinoma Pancreatic DuctalPancreas
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Upconversion Nanocarriers Encapsulated with Photoactivatable Ru Complexes for Near-Infrared Light-Regulated Enzyme Activity.

2017

Enzyme activity is important for metabolism, cell functions, and treating diseases. However, remote control of enzyme activity in deep tissue remains a challenge. This study demonstrates near-infrared (NIR) light-regulated enzyme activity in living cells based on upconverting nanoparticles (UCNPs) and a photoactivatable Ru complex. The Ru complex is a caged enzyme inhibitor that can be activated by blue light. To prepare a nanocarrier for NIR photoinhibition of enzyme activity, a UCNP and the caged enzyme inhibitors are encapsulated in a hollow mesoporous silica nanoparticle. In such a nanocarrier, the UCNP can harvest NIR light and convert it into blue light, which can activate the caged e…

Materials scienceCell SurvivalInfrared RaysCathepsin KNanoparticle02 engineering and technology010402 general chemistryPhotochemistry01 natural sciencesRutheniumBiomaterialsCell Line TumorLNCaPHumansGeneral Materials ScienceEnzyme Inhibitorsneoplasmschemistry.chemical_classificationbiologytechnology industry and agricultureGeneral ChemistryMesoporous silicaequipment and supplies021001 nanoscience & nanotechnologyPhoton upconversionEnzyme assay0104 chemical sciencesEnzymechemistryEnzyme inhibitorbiology.proteinNanoparticlesNanocarriers0210 nano-technologyBiotechnologySmall (Weinheim an der Bergstrasse, Germany)
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