20 research outputs found
Brain Environment
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ãžãšãªã¯ã«ãŒããã现èå€ãžã®æåºãä¿é²ããååã§ã¯ãªãããšèããŠããããã®éçšã¯ç¥çµçŽ°èã®ä¿è·ã«åãããéå°ã«ãªããšãšã¯ãœãœãŒã ã®æšçã§ããã°ãªã¢çŽ°èã«åŒ·ãççå¿çãæ¹èµ·ããè³ãã¡ãªã¹ã¿ã·ã¹ã®ç Žç¶»ã«ç¹ãããšäºæ³ããããç 究課é¡/é åçªå·:26111714, ç 究æé(幎床):2014-04-01 â 2016-03-3
Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer
Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show that while AXL-low expressing EGFR mutated lung cancer (EGFRmut-LC) cells are more sensitive to osimertinib than AXL-high expressing EGFRmut-LC cells, a small population emerge osimertinib tolerance. The tolerance is mediated by the increased expression and phosphorylation of insulin-like growth factor-1 receptor (IGF-1R), caused by the induction of its transcription factor FOXA1. IGF-1R maintains association with EGFR and adaptor proteins, including Gab1 and IRS1, in the presence of osimertinib and restores the survival signal. In AXL-low-expressing EGFRmut-LC cell-derived xenograft and patient-derived xenograft models, transient IGF-1R inhibition combined with continuous osimertinib treatment could eradicate tumors and prevent regrowth even after the cessation of osimertinib. These results indicate that optimal inhibition of tolerant signals combined with osimertinib may dramatically improve the outcome of EGFRmut-LC
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é沢倧åŠããçåœç§åŠç 究æWe have revealed that glioma-derived exosomes convey a tumor-related factor WT1 to microglial cells in the surrounding areas of a tumor leading to angiogenesis (generation of new blood vessels), which contributes to the creation of a microenvironment favorable for invasion and metastasis of a tumor.Using an intracranial implantation glioma mouse model, we first showed a longer survival time of mice through tumor size reduction and suppression of invasion and metastasis by repressing the production of exosomes by the glioma. Next, we showed that exosomes secreted from the glioma were taken up by the surrounding microglia thus regulating gene expression in microglia, thereby promoting angiogenesis. Furthermore, we showed that WT1, an expression regulator of that gene, was contained in tumor-derived exosomes of human patients and regulated the microglial ability of angiogenesis.ç¥çµè è
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µçŽ ãæŸåºãããèåšã»çµç¹é害ãåŒãèµ·ãããŠããã®ããMRIãçšããŠæããã«ããããã19Fããç²åãšã¬ããªããŠã é¯äœãçšããæ°èŠã¹ããŒããããŒããéçºãããSecretion of lysosomal enzymes from macrophages or neutrophils is called heterolysis, but what kind of physiological phenomena or pathological condition can be induced by heterolysis remains elusive. We recently identified a candidate molecule that regulates this process and confirmed that this molecule actually promotes heterolysis. When cardiovascular inflammation was induced in mice deficient in this molecule, the onset of cardiovascular inflammation was reduced as compared with the wild type mice. Furthermore, in order to clarify what type of lysosomal enzyme is actually released to cause organ and tissue damage in vivo by using MRI, we developed a new smart probe using 19F nanoparticles and a gadolinium complex.ç 究課é¡/é åçªå·:16K15231, ç 究æé(幎床):2015-04-01 - 2018-03-3
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