Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

The application of extracellular vesicles,particularly exosomes(EXs),is rapidly expanding in the field of medicine,owing to their remarkable properties as natural carriers of biological cargo.This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues(NAF-EXs)for personalized medicine,which can be derived at the time of diagnosis by endoscopic ultrasound.Herein,we show that exosomes(EXs)derived from NAFs demonstrate differential bio-physical characteristics,efficient cellular internalization,drug loading efficiency,pancreatic tumor targeting and delivery of payloads.NAF-derived EXs(NAF-EXs)were used for loading ormeloxifene(ORM),a potent anti-cancer and desmoplasia inhibitor as a model drug.We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype,which may be due to regulation of Ca^(2+) influx in fibroblast cells.NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition(EMT)and repressed tumor growth in xenograft mouse model.In conclusion,our data suggests preferential tropism of NAF-EXs for PDAC tumors,thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs.Additionally,it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

脑动脉粥样硬化的颅内血管成形和支架置入术：美国介入和治疗神经放射学学会、介入放射学学会和美国神经放射学学会的立场声明

在北美、欧洲和亚洲，卒中是第3位死亡原因和成人残疾的首要病因。颅内动脉粥样硬化所致的卒中约占所有缺血性卒中的8％～10％，据报道，在亚洲、非洲和西班牙裔人群中这一比例更高。其危险因素包括胰岛素依赖性糖尿病、高胆固醇血症、高血压和吸烟。在美国，估计每年有40000～60000例新发卒中是由于颅内动脉粥样硬化所致。