简介：Thisworkaimstoinvestigatetheeffectsofdosingregimentsondrugdeliveryinsolidtumorsandtovalidatethemwithexperimentsonrats.Thelumpedparametermodelsofpharmacokineticsandofdrugdeliveryintumorweredevelopedtosimulatetimecoursesofaveragedrugconcentration(Ct)oftumorinterstitiumintwotypesofdosingregiments(i.e.,single-shotandtriple-shotones).Thetworegimentswereperformedviaantitumordrug,hydroxycamptothecin(HCPT),onrats,tomeasurethedrugconcentrationinthetumor.Thesimulationsofthedrugconcentrationinthetumorofthetwodosingregimentswereconductedandcomparedwiththeexperimentaldataonrats.Thecoefficientsinthemodelswereinvestigated.Itisconcludedthatthetriple-shotmethodismoreeffectivethanthatofsingle-shotinjection.Thepresentlumped-parametermodelisquantitativelycompetentfordrugdeliveryinsolidtumor.

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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.

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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.

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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：作者在局部地凸的空格给稳固的锥的双描述。从这，作者为判定凸的锥在局部地凸的空格的各种各样的类型稳固获得一些标准。用一个稳固的锥的内部的一个一般表达式，作者获得很多个必要、足够的条件让凸的锥在Banach空格的框架稳固。特别地，作者给在稳固的锥和概括的锋利的锥之间的一种双关系。相关已知的结果被改进并且延长。

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简介：ＴＵＭＯＲＮＥＣＲＯＳＩＳＦＡＣＴＯＲ－αＡＬＴＥＲＳＰＲＯＴＥＩＮＭＥＴＡＢＯＬＩＳＭＡＮＤＣＥＬＬ－ＣＹＣＬＥＫＩＮＥＴＩＣＳＩＮＭＡＬＩＧＮＡＮＴＴＵＭＯＲＹｅＳｈｅｎｇｌｏｎｇ叶胜龙；ＴａｎｇＺｈａｏｙｏｕ汤钊猷；ＢｒｕｃｅＲＢｉｓｔｒｉａｎ...

简介：Thesolid-phasesynthesisofisoxazolineson2-polystyrylsulfonamidoethanolresinisreported.2-Polystyrylsuifonamidoethanolresin1wasreactedwithacryloylchloridetoafford2-polystyrylsulfonylamidoethylacrylateresin2,whichwasfurtherreactedwithbrominatedaldoximesby[3+2]cycioadditiontogiveisoxazolineresin4.Resin4wastreatedwithaqueous6mol/LHCIsolutiontoobtainisoxazolinesingoodyieldandpurity.

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：在这份报纸，稳固的粒子在的聚类的行为一二维(2D)liquidsolid使流体化床被使用费用学习测量并且处理技术的联合设备(电荷耦合器件)成像并且被分数维的分析描绘。在2Dliquidsolidfluidised床的稳固的粒子的分发不是制服和稳固的粒子的组织工会行为的电荷耦合器件图象表演在现在的试验性的条件下面被观察。稳固的粒子搬到在其配置经常在水平海滨形式的组或簇使流体化床的2D。簇的框分数维图形尺寸在2Dliquidsolid想象有与稳固的粒子直径和表面的液体速度的增长稳固的劫盗和还原剂升起的使流体化床的增加。在给定的稳固的劫盗和稳固的粒子尺寸，更轻的粒子显示出更小的分数维的尺寸。

简介：Tumormetastasisisthedominantcauseofdeathincancerpatients.However,themolecularandcellularmechanismsunderlyingtumormetastasisarestillelusive.Theidentificationofproteinmoleculeswiththeirexpressionscorrelatedtothemetastaticprocesswouldhelptounderstandthemetastaticmechanismsandthusfacilitatethedevelopmentofstrategiesforthetherapeuticinterventionsandclinicalmanagementofcancer.Proteomicsisasystematicresearchapproachaimingtoprovidetheglobalcharacterizationofproteinexpressionandfunctionundergivenconditions.Proteomictechnologyhasbeenwidelyusedinbiomarkerdiscoveryandpathogeneticstudiesincludingtumormetastasis.Thisarticleprovidesabriefreviewoftheapplicationofproteomicsinidentifyingmolecularfactorsintumormetastasisprocess.Thecombinationofproteomicswithotherexperimentalapproachesinbiochemistry,cellbiology,moleculargeneticsandchemistry,togetherwiththedevelopmentofnewtechnologiesandimprovementsinexistingmethodologieswillcontinuetoextenditsapplicationinstudyingcancermetastasis.

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简介：根据国家科学基金(NSF)主任A。Bement，鈥楾ransformative研究是承受极端地改变我们一个重要存在科学概念的理解或导致一个新范例的创造或科学的地的一个合理机会的想法驾驶的鈥?研究。鈥?被它对当前的理解的挑战也描绘或它到新边疆鈥?纳米技术的小径是如此的边疆之一。它是在强烈与原子、分子的相互作用联系的分子的水平鈥?现象的新材料，设备和系统的创造影响宏观的材料性质与显著地改进了机械、光、化学、电的鈥?性质。在2002的以前的NSF主任丽塔·科尔韦尔声明了，鈥榥anoscale技术将有一个影响平等者到工业Revolution'。超群的技术包括纳米技术，微电子学，信息技术和生物工学以及创新、支持的机械、民用的基础结构系统和材料。这些技术是二十第一个世纪和新经济的主要司机。力学是在所有超群的技术的一个必要元素。在力学研究机会，教育和挑战，包括在材料的nanomechanics，碳nano试管，启发简历的材料，燃料房间，以及改进工程和设计的试验性、数字、分析的方法在这被介绍并且讨论纸。

简介：ＳｏｌｉｄＭｏｄｅｌｉｎｇＥｒｏｒ：ＡｎａｌｙｓｉｓａｎｄＣｏｍｐｅｎｓａｔｉｏｎ①ＸｕＺｈｉｇａｎｇＨｕａｎｇＫｅｚｈｅｎｇＡｉＸｉｎｇＳｈａｎＬｉａｎｙｅＣｏｌｅｇｅｏｆＭｅｃｈａｎｉｃａｌＥｎｇｉｎｅｅｒｉｎｇ，ＳｈａｎｄｏｎｇＵｎｉｖｅｒｓｉ...

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