简介：Objective:Humanpancreaticcancerisoneofthemostcommonclinicalmalignancies.Theeffectofcomprehensivetreatmentbasedonsurgeryisgeneral.Theeffectsofchemotherapywerenotobviousmainlybecauseoflackoftargetingandchemoresistanceinpancreaticcancer.Thisstudyaimedtoinvestigatetheeffectsoffolatereceptor(FR)-mediatedgemcitabineFA-Chi-Gemnanoparticleswithacore-shellstructurebyelectrostaticsprayonpancreaticcancer.Methods:Inthisstudy,thelevelsofexpressionofFRinsixhumanpancreaticcancercelllineswerestudiedbyimmunohistochemicalanalysis.Theuptakerateofisothiocyanate-labeledFA-ChinanoparticlesinFRhighexpressioncelllineCOLO357wasassessedbyfluorescencemicroscopeandtheinhibitionrateofFAChi-GemnanoparticlesonCOLO357cellswasevaluatedbyMTTassay.Moreover,thebiodistributionofPEG-FA-ICGDER02-Chiintheorthotopicpancreatictumormodelwasobservedusingnear-infraredimagingandthehumanpancreaticcancerorthotopicxenograftsweretreatedwithdifferentnanoparticlesandnormalsalinecontrol.Results:TheexpressionofFRinCOLO357wasthehighestamongthesixpancreaticcancercelllines.TheFRmainlydistributedoncellmembraneandfewerinthecytoplasminpancreaticcancer.Moreover,theabsorptionrateoftheFA-Chi-GemnanoparticleswasmorethantheChinanoparticleswithoutFAmodified.TheproliferationofCOLO357wassignificantlyinhibitedbyFA-Chi-Gemnanoparticles.ThePEG-FAICGDER02-Chinanoparticleswereenrichedintumortissueinhumanpancreaticcancerxenografts,whilenon-targetednanoparticlesweremainlyinnormallivertissue.PEG-FA-Gem-Chisignificantlyinhibitedthegrowthofhumanpancreaticcancerxenografts(PEG-FA-Gem-Chivs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-ChinanoparticlesmightbeaneffectivetargeteddrugfortreatinghumanFR-positivepancreaticcancer.

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简介：AbstractTo compare efficacy and safety of nab-paclitaxel plus gemcitabine (AG) with nab-paclitaxel plus S-1 (AS) as first-line treatment for metastatic pancreatic cancer, we conducted a retrospective analysis by reviewing medical records of 53 metastatic pancreatic cancer patients in our institution. They received either AG (nab-paclitaxel 125 mg/m2 on days 1, 8 and gemcitabine 1000 mg/m2 on days 1, 8) or AS (nab-paclitaxel 125 mg/m2 on days 1, 8 and S-1 80-120 mg on days 1-14) chemotherapy. We found that AS had higher objective response rate (36% vs 21.4%), better disease control rate (84% vs 75%), prolonged time to progression (TTP, 7.1 vs 5 months), and improved overall survival (OS, 15.3 vs 12 months) when compared with AG. In Cox proportional hazards model, sex was significantly associated with TTP (P value=.031) and metastatic sites plus treatment after progression were significantly associated with OS (P value=.028 and .01, respectively). The incidence rate of chemotherapy-related adverse events was similar in both groups. Neutropenia (50% and 60%, all grade; 21.4% and 36%, grade 3 or 4, in AG and AS group) and sensory neuropathy (21.4% and 24%, all grade; 3.6% and 4%, grade 3 or 4, in AG and AS group) were the most common hematologic and non-hematologic toxicity. Thus, we believed that AS is a reasonable and convenient alternative for patients treated with AG as first-line chemotherapy for metastatic pancreatic cancer.