简介：AbstractThe tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.

简介：Objective:Variousnanoparticleshavebeendesignedandtestedinordertoselectoptimalcarriersfortheinhalationdeliveryofanticancerdrugstothelungs.Methods:Thefollowingnanocarrierswerestudied:micelles,liposomes,mesoporoussilicananoparticles(MSNs),polypropyleneimine(PPI)dendrimer-siRNAcomplexesnanoparticles,quantumdots(QDs),andpoly(ethyleneglycol)polymers.Allparticleswerecharacterizedusingthefollowingmethods:dynamiclightscattering,zetapotential,atomicforcemicroscopy,invitrocyto-andgenotoxicity.Invivoorgandistributionofallnanoparticles,retentioninthelungs,andanticancereffectsofliposomesloadedwithdoxorubicinwereexaminedinnudemiceafterthepulmonaryorintravenousdelivery.Results:Significantdifferencesinlunguptakewerefoundaftertheinhalationdeliveryoflipid-basedandnon-lipid-basednanoparticles.Theaccumulationofliposomesandmicellesinlungsremainedrelativelyhigheven24hafterinhalationwhencomparedwithMSNs,QDs,andPPIdendrimers.Therewerenotabledifferencesbetweennanoparticleaccumulationinthelungsandotherorgans1and3hafterinhalationorintravenousadministrations,but24hafterintravenousinjectionallnanoparticlesweremainlyaccumulatedintheliver,kidneys,andspleen.Inhalationdeliveryofdoxorubicinbyliposomessignificantlyenhanceditsanticancereffectandpreventedsevereadversesideeffectsofthetreatmentinmicebearingtheorthotopicmodeloflungcancer.Conclusion:Theresultsofthestudydemonstratethatlipid-basednanocarriershadconsiderablyhigheraccumulationandlongerretentiontimeinthelungswhencomparedwithnon-lipid-basedcarriersaftertheinhalationdelivery.Theseparticlesaremostsuitableforeffectiveinhalationtreatmentoflungcancer.

简介：AbstractThis review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of "gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome." Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.

简介：AIM:Toinvestigatethelifetimeriskofdevelopmentofesophagealadenocarcinomaand/orhigh-gradedysplasiainpatientsdiagnosedwithBarrett’sesophagus.METHODS:DatawereextractedfromtheUnitedKingdomNationalBarrett’sOesophagusRegistryondateofdiagnosis,patientageandgenderof7877patientsfromwhohadbeenregisteredfrom35UnitedKingdomcenters.LifeexpectancywasevaluatedfromUnitedKingdomNationalStatisticsdatabasedupongenderandageatyearatdiagnosis.Thesedatawerethenusedwithpublishedestimatesofannualadenocarcinomaandhigh-gradedysplasiaincidencesfrommetaanalysesandlargepopulation-basedstudiestoestimateoveralllifetimeriskofdevelopmentofthesestudyendpoints.RESULTS:ThemeanageatdiagnosisofBarrett’sesophaguswas61.6yearsinmalesand67.3yearsinfemales.Themeanlifeexpectancyatdiagnosiswas23.1yearsinmales,20.7yearsinfemalesand22.2yearsoverall.Usingdatafrompublishedmeta-analyses,thelifetimeriskofdevelopmentofadenocarcinomawasbetween1in8and1in14andthelifetimeriskofhigh-gradedysplasiaoradenocarcinomawas1in5to1in6.Usingdatafrom3largerecentpopulation-basedcohortstudiesthelifetimeriskofadenocarcinomawasbetween1in10and1in37andofthecombinedendpointofhigh-gradedysplasiaandadenocarcinomawasbetween1in8and1in20.AgeatBarrett’sesophagusdiagnosisisreducingandlifeexpectancyisincreasing,whichwillpartiallycounter-balancelowerannualcancerincidence.CONCLUSION:Thereisasignificantlifetimeriskofdevelopmentofhigh-gradedysplasiaandadenocarcinomainBarrett’sesophagus.

简介：AbstractIntroduction:Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that disproportionately affects geriatric patients. Combination therapy with surgery and chemotherapy is associated with longer survival than medical treatment or supportive care. Preoperative selection of patients for surgical treatment, based on patient-specific factors such as sarcopenia, may help risk-stratify patients and improve outcomes. This paper aims to review the current literature on the impact of sarcopenia and sarcopenic obesity on patients undergoing treatment for PDAC.Outcomes:The impact of sarcopenia and sarcopenia obesity on perioperative and long-term outcomes after treatment for PDAC is variable. Sarcopenia has been associated with high-grade complications, longer length of hospital, and intensive care unit stays, more frequent discharge to skilled nursing facilities and decreased utilization of adjuvant therapy in patients treated with curative intent surgery. Sarcopenic obesity has been associated with more complications, high-grade complications, and hematologic toxicities. Patients with sarcopenic obesity may have even lower overall survival than sarcopenic patients.Discussion:The effect of a pre-treatment diagnosis of sarcopenia or sarcopenic obesity on outcomes for patients undergoing treatment for PDAC remains unknown, in part due to the heterogeneity of studies and definitions. Prehabilitation programs including resistance exercise and nutritional supplementation have shown benefit in sarcopenic patients.Conclusion:PDAC remains a deadly disease and patient-specific factors such as sarcopenia and sarcopenic obesity identified at the time of cancer diagnosis offer potential as risk stratification measures and points of intervention. Currently, a paucity of standardized measurement tools, definitions, and prehabilitation regimens limits the clinical implementation of such knowledge.

简介：DearEditor,Adenocarcinomaofthenonpigmentedciliaryepithelium(NPCE)isararemalignanttumorwhichisnoteasytobefoundintheearlystage~([1]).Herein,wereportacaseofadenocarcinomaoftheNPCEinaChineseboyanddiscussits

简介：AbstractExtracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.

简介：Differentapproachesfortreatinglungcancerhavebeendevelopedovertime,includingchemotherapy,radiotherapyandtargetedtherapiesagainstactivatingmutations.Lately,betterunderstandingoftheroleoftheimmunologicalsystemintumorcontrolhasopenedmultipledoorstoimplementdifferentstrategiestoenhanceimmuneresponseagainstcancercells.Itisknownthattumorcellseludeimmuneresponsebyseveralmechanisms.Thedevelopmentofmonoclonalantibodiesagainstthecheckpointinhibitorprogrammedcelldeathprotein1(PD-1)anditsligand(PD-L1),onTcells,hasledtohighactivityincancerpatientswithlonglastingresponses.Nivolumab,anantiPD-1inhibitor,hasbeenrecentlyapprovedforthetreatmentofsquamouscelllungcancerpatients,giventhesurvivaladvantagedemonstratedinaphaseIIItrial.Pembrolizumab,anotherantiPD-1antibody,hasreceivedFDAbreakthroughtherapydesignationfortreatmentofnon-smallcelllungcancer(NSCLC),supportedbydatafromaphaseItrial.ClinicaltrialswithantiPD-1/PD-L1antibodiesinNSCLChavedemonstratedverygoodtolerabilityandactivity,withresponseratesaround20%andamediandurationofresponseof18months.

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简介：AbstractImmunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.

简介：肺上皮是在各种各样的肺疾病的肺损坏的主要地点。上皮的房间apoptosis被认为是在各种各样的肺疾病的起始的事件。发信号的Apoptosis古典主义地由二条原则小径组成。一个人是从死亡受体结扎的一条直接小径到caspase串联激活和房间死亡。象药，放射，传染代理人和反应的氧种类那样的压力触发的另外的小径被线粒体调停。Endoplasmic蜂窝胃也被显示了是细胞器调停apoptosis.Epithelial房间死亡被改变过程跟随，它由组成上皮并且成纤维细胞激活，cytokine生产，凝结小径的激活，neoangiogenesis，re-epithelialization和fibrosis.Epithelial和间充质的相互作用在这些过程起重要作用。apoptosis由新奇策略发信号和它的规定的进一步的理解可以对各种各样的肺疾病导致有效治疗。我们在apoptosis发信号的理解考察最近的进展并且在肺改变讨论apoptosis的参与。

简介：FromNovember1,2013,TranslationalLungCancerResearch(TLCR)isofficiallyendorsedbytheSpanishLungCancerGroup(Figure1).ThisisameaningfulmilestoneforTLCRasanacknowledgmentofitsexpansionanddedicationtolungcancerresearchandwilltremendouslyadvanceitscontinuedexplorationinthefield.SinceitwaslaunchedinMay2013,TLCRhasbeendedicatedtoprovidingcutting-edgefindingsintherapidly

简介：AIM:TopreparepolylacticacidmicrospheresofErythromycinforLungtargeting.METHEDS:Theorthogonaltestdesignwasusedtooptimizethetechnology,ofpreparation.Thecharacterofthemicrospheres,drugreleaseinvitro,stabilityandtissuedistributionwereexaminedRESULTS:TheErythromycinpolylacticacidmicrosphereswasregularinitsmorphology.DrugwasenvelopedinmicrospheresbutnotphysicallymixedwithPDLLA.Theaverageparticlesizewas11.65μnwithover94%ofthemicrospheresbeingintherangeof5～20trn;Thedrugloadingandtheincorporationefciencywere18%and60%respectively.Themicrosphereswerestableforthreemonthat4℃androomtemperature.TheinvitroreleasepropertiescouldbeexpressedbytheHiguchi'sequation:y=28.067+3.8515t11/2(r=0.9834).Comparingwithinjection,thedruginmicrosphereswasmoreconcentratedinlungtissue.CONCLUSION:Erythromycinpolylacticacidmicrospheresshowedsignificantsustainedreleaseandlungtargeting.

简介：LyingatthesouthernfootofMountJishiinJishishanCountyborderingGansuandQinghaiProvinces,Hor-sTag-lungMonastery(thereafterabbreviatedtosTag-lungMonastery)isawell-knownTibetanBuddhistmonasterybuiltintheearlyperiodofTibetanBuddhism.Ithasahistoryofmorethan400yearsandwasaffiliatedwithbKra-shis-lhun-poMonastery.Its

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简介：摘要：目的：探讨靶向+全脑治疗在肺腺癌EGFR敏感突变多发脑转移患者中的疗效与安全性。方法：选取2018年1月到2020年1月我院就诊的肺腺癌EGFR敏感突变多发脑转移患者共70例作为研究对象，随机分为两组各

简介：AIM:Toclarifythecorrelationwithphenotypicexpression,clinicopathologicalfeatures,geneticalterationandmicrosatellite-instabilitystatusinsmallintestinaladenocarcinoma(SIA).METHODS:Thecasesof47patientsdiagnosedwithprimarySIAsthatweresurgicallyresectedatourinstitutionin1975-2005werestudied.Wereviewedclinicopathologicalfindings(age,gender,tumorsize,grossappearance,histologicalmorphologictype,invasiondepth,lymphaticpermeation,venousinvasion,andlymphnodemetastasis),andtheimmunohistochemicalexpressionofMUC5AC,MUC6,MUC2,CD10,andmismatch-repair(MMR)proteins(MLH1andMSH2).WeanalyzedKRASandBRAFgenemutations,andthemicrosatelliteinstability(MSI)status.TheimmunohistochemicalstainingofCD10,MUC2,MUC5ACandMUC6wasconsideredpositivewhendistinctstainingin>5%oftheadenocarcinomacellswasrecorded.ToevaluateofMMRproteinexpression,weusedadjacentnormaltissueincludinglymphoidfollicles,inflammatorycells,andstromalcellsasaninternalpositivecontrol.SectionswithoutnuclearstaininginthetumorcellswereconsideredtohavelosttheexpressionoftherespectiveMMRprotein.RESULTS:Therewere29malesand18femalespatients(meanage59.9years,range:23-87years).Tumorswerelocatedintheduodenumin14cases(30%),thejejunumin21cases(45%),andtheileumin12cases(25%).Aphenotypicexpressionanalysisrevealed20MUC2-positivetumors(42.6%),11MUC5AC-positive(23.4%),4MUC6-positive(8.5%),and7CD10-positive(14.9%).ThetumorsizesoftheMUC2(+)tumorsweresignificantlylargerthanthoseoftheMUC2(-)tumors(mean,5.7±1.4cmvs4.7±2.1cm,P<0.05).AllthreetumorswithadenomatouscomponentwerepositiveforMUC2(P<0.05).PolypoidappearancewasseensignificantlymorefrequentlyintheCD10(+)groupthanintheCD10(-)group(P<0.05).ThetumorsizewassignificantlylargerintheCD10(+)groupthanintheCD10(-)group(mean,5.9±1.4cmvs5.0±2.1cm,P<0.05).Of34SIAswithsuccessfullyobtainedMSIdata,4wereMSI-high.O

简介：Apocrinecarcinomaisararemalignantadnexalneoplasm.Thedifferentialdiagnosisbetweenapocrinecarcinomaandcutaneousmetastasisisoftendifficult.Here,wereportacaseoflocallyrecurrentpenileapocrinecarcinomainitiallydiagnosedasmetastaticadenocarcinomaofthecolon.A75-year-oldmanwithahistoryofsurgicalresectionduetosigmoidcoloncancerandpenilemetastasistwoyearspriortothisstudypresentedwithanoduleattheleftpenilebase.Heunderwentawidelocalresectionofthepenilemassunderasuggestedpreoperativediagnosisofextra-mammaryPaget’sdisease(EMPD)associatedwithprevioussigmoidcoloncancer.However,thepreviouslyandcurrentlyresectedpenilemasseswereidentifiedasprimaryapocrinecarcinomauponhematoxylinandeosin(H&E)stainingandimmunohistochemicalstaining.Althoughtheincidenceisextremelyrare,bothcliniciansandpathologistsshouldbealerttothepossibilityofsynchronousdoubleprimaryapocrinecarcinomaincancerpatientswithmalignantcutaneouslesions.

简介：AbstractPancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies, and the majority of patients with PDAC present with metastatic disease, mainly in the liver, at the time of diagnosis. Surgical resection is the only treatment that can offer prolonged survival and possible cure. However, the indications for surgery for patients with PDAC metastases remain extremely limited to highly selected patients with localized disease, and metastatic disease is generally regarded as a contraindication to surgery. Recently, however, the advent of more effective chemotherapy has changed the treatment strategy for metastatic PDAC. In fact, cases in which resection of synchronous or metachronous PDAC liver metastases lead to prolonged survival in highly selected patients have been reported. In this review, we provide current data regarding survival outcomes after surgery, and discuss the role of surgical resection and selection criteria for patients with PDAC liver metastases in the modern era.