简介:AbstractThe contemporary embrace of endoscopic technology in the approach to the anterior skull base has altered the perioperative landscape for patients requiring pituitary surgery. Utility of a multi-disciplinary unit in management decisions facilitates the delivery of optimal care. Evolution of technology and surgical expertise in pituitary surgery mandates ongoing review of all components of the care central to these patients. The many areas of potential variability in the pre, intra and post-operative timeline of pituitary surgery are readily identifiable. Core undertakings and contemporary controversies in the peri-operative management of patients undergoing endoscopic transsphenoidal pituitary surgery are assessed against the available literature with a view to providing guidance for the best evidence-based practice.
简介:AsanewmemberofIAP(inhibitorsofapoptosisprotein)family,survivinhaspotentanti-apoptoticactivities,andinvolvesinthemitosisandangiogenesis.Researcheshavedemonstratedthatsurvivingisatumor-specificanti-apoptoticfactor,expressedinfetaltissues,andcommonhumancancers,whilenotinnormal,terminallydifferentiatedadulttissues.Theoverexpressionofsurvivinintumortissuesiscorrelatedwithpoorprognosisofthepatients.Survivincanbeusedasaprognosticfactorandanewtargetintumortargetingtherapy.
简介:Thegeneralprinciplefortumorcellstoescapefromimmunesurveillanceistopreventtumorantigensfrombeingrecognizedbytheimmunesystem.Manymethodshavebeendevelopedtoincreasetheimmunogenecityofthetumorcells.Themostefficientmethodsareabletoforcetumorcellstopresenttheirowntumorantigenstotheimmunesystem.StimulatingThcellsbyconvertingtumorcellsintoMHCclassⅡ+/Ii-antigenpresentingcellsisoneofthemostefficienttechnologies.Usingantisensemethods,wesuppresstheexpressionoftheIiproteinthatnormallyco-expresseswithMHCclassⅡmoleculesandblockstheantigenicpeptidebindingsiteofMHCclassⅡmoleculesduringsynthesisintheendoplasmicreticulum.Insuchtumorcells,the'unprotected'MHCclassⅡmoleculespickupendogenoustumorantigenicpeptides,whichhavebeentransportedintotheERforbindingtoMHCclassⅠmolecules.SimultaneouspresentationoftumorantigensbybothMHCclassⅠandⅡmoleculesgeneratesarobustandlong-lastinganti-tumorimmuneresponse.MHCclassⅡ+/Ii-tumorcellsarepotenttumorcellvaccinesandalsocureasignificantnumberofanimalswithrenalandprostatetumors.Wehavedevelopedanalogoushumangenevectorsthataresuitableformostpatientsandcancers.
简介:Tumor-targetingantibodieswereinitiallydefinedasagroupoftherapeuticmonoclonalantibodies(mAb)thatrecognizetumor-specificmembraneproteins,blockcellsignaling,andinducetumor-killingthroughFc-driveninnateimmuneresponses.However,inthepastdecade,ampleevidencehasshownthattumor-targetingmAb(TTmAb)eradicatestumorcellsviaactivationofcytotoxicTcells(CTLs).Inthisreview,wespecificallyfocusonhowTTmAbsinduceadaptiveanti-tumorimmunityanditspotentialincombinationtherapywithimmunecytokines,checkpointblockade,radiation,andenzymetargetedsmallmoleculedrugs.ExploringthemechanismsofthesepreclinicalstudiesandretrospectiveclinicaldatawillsignificantlybenefitthedevelopmentofhighlyefficientandspecificTTmAb-orientedanti-tumorremedies.
简介:这研究是在RGD-FasL和内在的机制导致的垂体腺瘤房间线GH3/MMQ/AtT20上调查细胞毒素的效果。Fas/DcR3mRNAs被RT-PCR检测,他们的表面表情被流动cytometry测量。RGD-FasL在肿瘤房间上施加的Cytotoxicity与MTT试金被测量,导致的apoptosis被agarose胶化电气泳动决定。房间周期和apoptosis被流动cytometry估计,PI染色。caspase8/9/3,Bcl-2,RANKL和JNK2的表情被西方的弄污检测。约13.7%GH3房间,25.5%MMQ房间,,22.2%AtT20房间表示船边交货23.9%GH3房间,24.1%MMQ房间,4.6%AtT20房间表示DcR3。肿瘤房间上的FasL/RGD-FasL的细胞毒素的效果都以一种剂量依赖者方式被拿。房间线MMQ/AtT20至于FasL显示出一样的敏感到RGD-FasL,当房间线GH3对RGD-FasL不太敏感时。房间周期分析显示RGD-FasL能在G0/G1阶段和G2/M阶段禁止房间。在与RGD-FasL对待的MMQ和AtT20房间,AI不与,在与RGD-FasL对待的GH3房间与FasL对待那显著地不同,AI比与FasL对待的低。当Bcl-2的与RGD-FasL在处理以后被减少时,caspase-8/9/3,RANKL和JNK2的表情被增加,建议RGD-FasL导致通过caspase激活的apoptosis。我们断定RGD-FasL能可能被看作垂体腺瘤的处理的一个新奇therapeutical候选人。
简介:AbstractBackground:Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.Methods:Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 105 colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in the tumor tissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction.Results:The results showed that local inflammation induced by foreign body implantation suppressed tumor growth with decreased tumor weight (P = 0.001), volume (P = 0.004) and Ki67 index (P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased (P = 0.040), while CD4+ T cells slightly increased in the tumor tissues of the group of foreign body-induced local inflammation (P = 0.035). Moreover, the number of M1 macrophages (P = 0.040) and expression of TLRs, especially TLR3 (P < 0.001) and TLR4 (P < 0.001), were significantly up-regulated in the foreign body group. Contrarily, tumor growth was significantly promoted in LPS or PolyIC-induced systemic inflammation (P = 0.009 and 0.006). FCM results showed M1 type macrophages (P = 0.017 and 0.006) and CD8+ T cells (P = 0.031 and 0.023) were decreased, while M2 type macrophages (P = 0.002 and 0.007) were significantly increased in tumor microenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group.Conclusions:The foreign body-induced local inflammation inhibited tumor growth, while LPS or PolyIC-induced systemic inflammation promoted tumor growth. The results suggested that the different outcomes of tumor growth might be attributed to the infiltration of anti-tumor or pro-tumor immune cells, especially M1 or M2 type macrophages into tumor microenvironment.
简介:TheundecapeptidesubstanceP(SP)wasshowntobeintimatelyinvolvedinboththestructuralandfunctionalaspectsoftheanteriorpituitary.Yet,inadditiontoitsinfluencesonhormonalsecretion,SPmaywellpossessmoreactionsinthismastergland.ThepresentstudywasfthereforeaimedtoinvestigatetheeffectofSPontheproliferationofratanteriorpituitarycellsinprimaryculture,ItwasfoundthatSPcoulddose-dependentlyincreasetheincorporationoftritiatedthymidine(3H-TdR)intoculturedanteriorpituitarycells.OthermammaliantachykininssuchasneurokininAandneurokininBhadsimilareffectbuttovaryingdegrees.TheequipotentanalogueofSP,Norleucine^11-SP(Nle^11-SP),alsoactedlikewise.withitsactionantagonizablebyspantide,aSPreceptorblocker.TofurthercharacterizethenatureofcellsresponsivetothechallengeofSP,immunocytochemicalstainingagainstS-100proteinandsomeadenohypophysealhormoneswasperformedaloneorplusautoradiography.TheresultsshowedthatthepercentageofS-100proteinimmunorectivecellswasapparentlyelevatedbytheaddtionofNle^11-Spfor48h,whichindicatesapreferentialproliferationoffolliculo-stellatecellsundertheregime.ThiswasconfirmedbyincreasesinimmunocytochemicalorautoradiographicallabellingindicesofanteriorpituitarySubstancePandanteriorpituitarycellproliferation.Cellstreatedsimilarly.Takentogether,TheseresultsrevealthatthetrophicactionofSPobservedpreviouslyinothertissuesisalsopresentatleastinculturedratanteriorpituitarycells.withrespondingcellsbeingpredominantlyfolliculo-stellatecellsastypifiedbyS-100proteinimmunoreactivity.Therefore,anintra-pituitarytrophicactionofSPinvivocouldbeanticipated.
简介:AbstractBackground:Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.Methods:Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s t test.Results:Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).Conclusion:These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.
简介:Tumormetastasisisthedominantcauseofdeathincancerpatients.However,themolecularandcellularmechanismsunderlyingtumormetastasisarestillelusive.Theidentificationofproteinmoleculeswiththeirexpressionscorrelatedtothemetastaticprocesswouldhelptounderstandthemetastaticmechanismsandthusfacilitatethedevelopmentofstrategiesforthetherapeuticinterventionsandclinicalmanagementofcancer.Proteomicsisasystematicresearchapproachaimingtoprovidetheglobalcharacterizationofproteinexpressionandfunctionundergivenconditions.Proteomictechnologyhasbeenwidelyusedinbiomarkerdiscoveryandpathogeneticstudiesincludingtumormetastasis.Thisarticleprovidesabriefreviewoftheapplicationofproteomicsinidentifyingmolecularfactorsintumormetastasisprocess.Thecombinationofproteomicswithotherexperimentalapproachesinbiochemistry,cellbiology,moleculargeneticsandchemistry,togetherwiththedevelopmentofnewtechnologiesandimprovementsinexistingmethodologieswillcontinuetoextenditsapplicationinstudyingcancermetastasis.
简介:AbstractGlioblastoma (GBM) is the most common primary malignancy of the central nervous system in adults. The prognosis for late-stage glioblastoma (World Health Organization grade IV astrocytic glioma) is very poor. Novel treatment options are sought after and evaluated by clinicians and researchers, and remarkable advances have been made in surgical techniques, radiotherapy, and chemotherapy. However, the treatment of glioblastoma remains extremely difficult and it can extend the lives of patients by only a few months. There has been notable progress in the field of immunotherapy, particularly with the use of tumor vaccines, for treating glioblastoma; especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines and tumor cell vaccines. However, the results of the current clinical trials for vaccination are not satisfactory. This article reviews the progress in the development of vaccines for glioblastoma.
简介:Someantitumoractivitiesofcomponent(E),extractedfromtherootofFagopynumCymosum(Trev)Meisn(FCTM),haverecentlybeendiscoveredinvivoandinvitro.ThecomponentE(CE)’spatternofactionwithtumorcellularDNAatthemolecularpharmacologicallevelwasinvestigatedbymacromolecularsynthesisexperiment(MSE)andhumanDNAinteractionsystemestablishedinourlaboratory.Theexperimentsdemonstratedthat,invitro,theagentcouldmarkedlyinhibittheincorporationof3H-TdRintothecellularDNA,andtheIC50inP388leukemiacellandinSGC-7901cellwas17.86μg/mland110.4μg/ml,respectively.Theagent,atmg/mllevel,couldproduceanintercalationreversionpatternwithDNAwithinashorttime(2hours).Butwhentheintervalwasprolongedforover4hours,theactionchangedtointercalationirreversiblepattern.Accordingtotheseobservations,theauthorsinferthatCEinteractswithDNAintwoways-directlyandindirectly.Theindirectaction,especiallyinlowconcentr