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Cancer stem cells: Involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics

World Journal of Gastroenterology 2014年第31期20卷 10790-10801页

作者： Cristiana Pistol Tanase Ana Iulia Neagu Laura Georgiana Necula Cristina Mambet Ana-Maria Enciu Bogdan Calenic Maria Linda Cruceru radu albulescu Department of Biochemistry-Proteomics Victor Babes National Institute of Pathology Stefan S Nicolau Institute of Virology Carol Davila University of Medicine and Pharmacy National Institute for Chemical Pharmaceutical Research and Development

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells(CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

关键词： Cancer stem cells Pancreatic cancer Cancer stem cells signaling pathways Targeted therapy miRNA

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Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms

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Acta Pharmaceutica Sinica B 2020年第10期10卷 1835-1845页

作者： Chunfang Xie Julien Slagboom Laura-Oana albulescu Govert W.Somsen Freek J.Vonk Nicholas R.Casewell Jeroen Kool Amsterdam Institute of Molecular and Life Sciences Division of BioAnalytical ChemistryDepartment of Chemistry and Pharmaceutical SciencesFaculty of ScienceVrije Universiteit AmsterdamAmsterdam 1081HVThe Netherlands Centre for Analytical Sciences Amsterdam(CASA) Amsterdam 1098 XHThe Netherlands Centre for Snakebite Research and Interventions Liverpool School of Tropical MedicineLiverpool L35QAUK Centre for Drugs and Diagnostics Liverpool School of Tropical MedicineLiverpool L35QAUK Naturalis Biodiversity Center Leiden 2333 CRThe Netherlands

Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite *** this study,we investigated the inhibiting effects of the small molecules varespladib(nonspecific phospholipase A2 inhibitor),marimastat(broad spectrum matrix metalloprotease inhibitor)and dimercaprol(metal ion chelator)against coagulopathic toxins found in Crotalinae(pit vipers)snake *** from Bothrops asper,Bothrops jararaca,Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography,followed by nanofractionation and mass spectrometry identification undertaken in *** of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under *** venom toxins were mostly identified as phospholipases A2,while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine *** was found to effectively inhibit most anticoagulant venom effects,and also showed some inhibition against procoagulant ***,marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant *** information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates,and highlights their potential as future snakebite treatments.

关键词： Snakebite Antivenom Varespladib Marimastat Dimercaprol Chelators Nanofractionation

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Independent and complementary bio-functional effects of CuO andGa_(2)O_(3) incorporated as therapeutic agents in silica-and phosphate-based bioactive glasses

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Journal of Materiomics 2022年第4期8卷 893-905页

作者： T.Tite A.C.Popa B.W.Stuart H.R.Fernandes I.M.Chirica G.A.Lungu D.Macovei C.Bartha L.albulescu C.Tanase S.Nita N.Rusu D.M.Grant J.M.F.Ferreira G.E.Stan National Institute of Materials Physics MagureleRO-077125Romania Advanced Materials Research Group Faculty of EngineeringUniversity of NottinghamNG72RDUK CICECOdAveiro Institute of Materials Department of Materials and Ceramics EngineeringUniversity of Aveiro3810-193AveiroPortugal “Victor Babes”National Institute of Research and Development in Pathology and Biomedical Sciences BucharestRO-050096Romania National Institute for Chemical Pharmaceutical Research and Development BucharestRO-031299Romania

The incorporation of therapeutic-capable ions into bioactive glasses(BGs),either based on silica(SBGs)or phosphate(PBGs),is currently envisaged as a proficient path for facilitating bone *** with this view,the single and complementary structural and bio-functional roles of CuO andGa_(2)O_(3)(in the 2e5 mol%range)were assessed,by deriving a series of SBG and PBG formulations startingfrom the parent glass systems,FastOs®BG e 38.5SiO2d36.1CaOd5.6P2O5d19.2MgOd0.6CaF2,and50.0P2O5d35.0CaOd10.0Na_(2)Od5.0 Fe2O_(3)(mol%),respectively,using the process of *** inter-linked physico-chemistry e biological response of BGs was assessed in search of bio-functional *** light was shed on the structural role e as network former or modifier e ofCu and Ga,immersed in SBG and PBG *** preliminary biological performance was surveyedin vitro by quantification of Cu and Ga ion release under homeostatic conditions,cytocompatibility assays(in fibroblast cell cultures)and antibacterial tests(against Staphylococcus aureus).The similar(Cu)anddissimilar(Ga)structural roles in the SBG and PBG vitreous networks governed their ***,Cuions were leached in similar concentrations(ranging from 10e35 ppm and 50e110 ppm at BG doses of 5and 50 mg/mL,respectively)for both type of BGs,while the release of Ga ions was 1e2 orders ofmagnitude lower in the case of SBGs(i.e.,0.2e6 ppm)compared to PBGs(i.e.,9e135 ppm).This wasattributed to the network modifier role of Cu in both types of BGs,and conversely,to the network former(SBGs)and network modifier(PBGs)roles of *** glasses were cytocompatible at a dose of 5 mg/mL,while at the same concentration the antimicrobial efficiency was found to be accentuated by the coupledrelease of Cu and Ga ions from *** collective assessment,the most prominent candidate material forthe further development of implant coatings and bone graft substitutes was delineated as the38.5SiO2d34.1CaOd5.6P2O5d16.2MgOd

关键词： Bioactive glass Copper Gallium Structure Ion release Antibacterial

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