| 1 | NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2^(V617F)-positive myeloproliferative neoplasm cells显示文摘Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms(MPN);in this pathway,IRS2 is involved in the malignant transformation induced by JAK2^(V617F),and upregulation of IGF1R signaling induces the MPN phenotype.NT157,a synthetic compound designed as an IGF1R-IRS1/2 inhibitor,has been shown to induce antineoplastic effects in solid tumors.Herein,we aimed to characterize the molecular and cellular effects of NT157 in JAK2^(V617F)positive MPN cell lines(HEL and SET2)and primary patient hematopoietic cells.In JAK2^(V617F)cell lines,NT157 decreased cell viability,clonogenicity,and cell proliferation,resulting in increases in apoptosis and cell cycle arrest in the G2/M phase(p<0.05).NT157 treatment inhibited IRS1/2,JAK2/STAT,and NFκB signaling,and it activated the AP-1 complex,downregulated four oncogenes(CCND1,MYB,WT1,and NFKB1),and upregulated three apoptotic-related genes(CDKN1A,FOS,and JUN)(p<0.05).NT157 induced genotoxic stress in a JAK2/STAT-independent manner.NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients(p<0.05).These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN. | Bruna Alves Fenerich Jaqueline Cristina Fernandes Ana Paula Nunes Rodrigues Alves Juan Luiz Coelho-Silva Renata Scopim-Ribeiro Priscila Santos Scheucher Christopher A.Eide Cristina E.Tognon Brian J.Druker Eduardo Magalhães Rego João Agostinho Machado-Neto Fabiola Traina | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 4 | Composite particles with magnetic properties,near-infrared excitation,and far-red emission for luminescence-based oxygen sensing显示文摘Oxygen sensing,magnetic,and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing,baking,and grinding procedure.Upconverting nanocrystals are used as an excitation source and an oxygen indicator with far-red emission.The composite particles are excited with near infrared(NIR)laser light(980 nm).The visible upconversion emission is converted into an oxygen concentration-dependent far-red emission(<750 nm)using an inert mediator dye and a platinated benzoporphyrin dye.This concept combines the advantages of NIR excitation and far-red emissive indicator dyes,offering minimized auto-fluorescence and enhanced membrane permeability.Additional functionality is obtained by incorporating magnetic nanoparticles into the composite particles,which enables easy manipulation and separation of the particles by the application of an external magnetic field. | Elisabeth Scheucher Stefan Wilhelm Otto SWolfbeis Thomas Hirsch Torsten Mayr | 2015 | Microsystems & Nanoengineering2015，1，1： | 0 |
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