幽门螺杆菌感染对胃癌患者血管生成相关因子表达的影响

研究幽门螺杆菌(Helicobacter pylori,Hp)感染促血管生成素2(angiopoietin2,Ang2)及其受体Tie2、CD34和HER-2/neu蛋白的表达的影响,以探讨Hp诱导胃癌发生发展的可能机制,并寻找胃癌可能的肿瘤标记物。胃癌病人Hp阳性13例,阴性16例,取病灶组织,应用免疫组化方法检测Ang-2、Tie2、CD34和HER-2/neu蛋白的表达。同时将产幽门螺杆菌毒力因子(cytotoxin-associated gene A,cagA)的Hp培养滤液加入胃癌细胞(MGC-803)及正常胃粘膜上皮细胞(GES-1)的培养基中,48 h后应用流式细胞仪检测Tie2、HER-2/neu蛋白的表达。免疫组化结果显示与Hp阴性胃癌组相比,Hp阳性组Ang2和Tie2的阳性表达率均显著升高;流式检测结果显示:幽门螺杆菌毒力因子的添加导致MGC-803细胞中HER-2/Neu的表达显著增加(P<0.05),而正常胃粘膜GES-1细胞Neu表达无明显变化。上述结果表明Ang2及其受体Tie2参与了Hp诱导的胃癌发生发展,对两者的检测可能预示胃癌的发生,含CagA蛋白的幽门螺杆菌培养滤液单独作...     

促血管生成素在肿瘤血管生成中的作用

促血管生成素(angiopoietin，Ang)是近年来发现的唯一的一个含有受体激动剂和受体抑制剂的血管生长因子家族。目前发现的Ang家族共有4个成员，包括Ang-1，2，3，4，其与它们的共同受体Tie-2结合产生不同的作用，Ang-1和Ang-4能够激活Tie-2，而Ang-2和Ang-3拮抗Ana-1的功能。Ang家族与血管内皮生长因子(VEGF)调节通路协同作用，共同促进机体血管形成，     

土贝母苷甲在非小细胞肺癌异种移植鼠模型中抑制肿瘤血管生成的研究

目的 研究土贝母苷甲对肿瘤血管生成的影响及相应的分子机制.方法 将20只CD-1裸鼠随机分为对照组(生理盐水)和土贝母苷甲组(TBMS-I),每组各10只;皮下注射接种非小细胞肺癌(NSCLC)浓度为l×107/ml的NCI-H460单细胞悬液100μl,接种1d后开始腹腔给药,TBMS-I给药浓度为5 mg/kg,1/d,绘制肿瘤生长曲线,并对瘤体积和瘤重进行统计学分析;观察瘤内微血管密度;采用WST-1检测TBMS-I对内皮细胞、肿瘤细胞的抑制作用;Western blot检测TBMS-I对裸鼠内皮细胞eEND2的VEGFR-2 (KDR)和Tie2的表达的影响.结果 TBMS-I可显著抑制NSCLC的形成,减少瘤内血管密度,诱导内皮细胞凋亡且不减弱肿瘤细胞的活性,降低裸鼠内皮细胞eEND2膜上VEGFR-2(KDR)和Tie2的表达,与对照组比较差异均有统计学意义(P＜0.05).结论 TBMS-I能够抑制肿瘤血管的生成,其作用机制可能与下调VEGF/VEGFR2和Ang2/Tie2信号传导途径相关.     

血管内皮生长因子及受体Flt-1在膀胱癌中的表达及意义

目的 探讨血管内皮生长因子(VEGF)及其受体Flt-1在膀胱癌血管生成中的作用及与膀胱癌分化程度的关系。方法 采用免疫组化S-P法对40例膀胱癌及5例正常膀胱组织中VEGF、Flt-1蛋白进行检测。结果 VEGF及其受体Fit-1主要分布在膀胱癌组织血管内皮细胞和癌细胞胞质内,VEGF及Fit-1在G3(低分化)膀胱癌血管内皮细胞和癌细胞中的表达高于G2(中分化)和G1(高分化)并且明显高于正常组织(P＜0.01)。结论VEGF和其受体Fit-1与膀胱肿瘤的分级和分期密切相关,可以作为判断膀胱癌生长和浸润的指标之一。     

依那普利对2型糖尿病大鼠血浆Ang II水平及血管、肾脏AT1受体表达的影响

目的研究依那普利对2型糖尿病大鼠血浆Ang II和AT₁受体表达的影响。方法用放射免疫法测定血浆Ang II水平，免疫组化法观察血管和肾脏AT₁受体表达。结果糖尿病大鼠血浆Ang II明显高于对照组，应用依那普利后大鼠血浆Ang II明显降低。免疫组化染色发现糖尿病大鼠血管内皮细胞、平滑肌细胞和肾脏AT₁受体表达明显增加，依那普利治疗组大鼠血管内皮细胞、平滑肌细胞和肾脏AT₁受体表达与正常组接近。结论糖尿病大鼠血浆Ang II升高，血管和肾脏AT₁受体表达增加，依那普利可降低糖尿病大鼠血浆Ang II水平，下调血管和肾脏AT₁受体表达。     

人脑动静脉畸形及贝伐单抗相关作用研究进展

人脑动静脉畸形是由供血动脉、异常血管、引流静脉构成的畸形血管团,与血管的异常增殖、新生有关.研究证实,VEGF、Notch4、EphrinB2与人脑动静脉畸形血管的发生、进展关系密切.其通路导致VEGF升高,影响血管内皮细胞增殖、迁移能力,进而使畸形血管进一步增生,或致血管发生破裂出血.目前对于其治疗有显微手术治疗、血管内栓塞治疗、立体定向放射治疗.三种方法各有利弊,具体选择哪种还需要综合考虑多方因素.我们考虑药物治疗,研究贝伐单抗对血管畸形的作用.贝伐单抗是VEGF的单克隆抗体,可阻断VEGF作用于内皮细胞,从而影响畸形血管的产生和进展.有报道称能部分正常化这些BAVM.因而有可能是一种BAVM的治疗手段.本文就VEGF、Notch4、EphrinB2通路与内皮细胞增殖迁移的作用机制和贝伐单抗的药物作用进行综述.     

脑动静脉畸形破裂出血的急性期显微手术治疗

目的：探讨脑动静畸形（CAVM）破裂出血急性期手术疗效和临床特征。方法：回顾分析30例CAVM破裂出血患者急性期的不同治疗方法和疗效。结果：30例中1期血肿清除联合CAVM显微切除术19例,1期单纯血肿清除联合2期CAVM显微切除术5例,血肿清除联合γ刀治疗2例,血肿清除联合栓塞术1例,双侧脑室外引流3例。30例中死亡3例,昏迷1例,其余患者神经功能较术前均有不同程度的改善。结论：CAVM破裂出血急性期外科手术的正确判断和恰当处理是关键,应争取在血肿清除同时切除畸形血管。     

HIF-2α和Tie2在乳腺癌中的表达及临床意义

目的 研究低氧诱导因子2α(HIF-2α)、血管生成素受体(Tie2)、微血管密度(MVD)在乳腺癌中的表达及临床意义.方法 采用免疫组化法检测41例乳腺癌组织(A组)及22例乳腺正常组织(B组)中HIF-2α、Tie2及MVD表达,RT-PCR方法检测HIF-2α mRNA和Tie2 mRNA表达水平,分析HIF-2α、Tie2表达与乳腺癌临床指标的关系.结果 与B组相比,A组HIF-2α、Tie2、MVD表达明显增加(P＜0.05).A组中HIF-2α mRNA、MVD表达均与Tie2 mRNA表达呈正相关(r=0.881、0.832,P＜0.05).HIF-2α、Tie2蛋白表达与肿瘤大小、淋巴结转移密切相关.结论 HIF-2α、Tie2在乳腺癌血管生成过程中起到了重要的作用,可作为判断肿瘤生物学行为指标之一.     

血管内皮生长因子、血管生成素与子宫内膜异位症的研究进展

目的研究血管内皮生长因子（vascular endothelial growth factor,VEGF）及血管生成素（angiopoietin,Ang）对子宫内膜异位症（Endometriosis,Ems）的治疗作用。方法比对VEGF和Ang对Ems的作用,及两者的相互作用。结果 VEGF在Ems患者的腹腔液、血清、在位及异位内膜组织均呈高表达;Ang与VEGF相互作用,共同促进血管形成。结论血管内皮生长因子是目前所知作用最强的一种促血管生成因子,抑制血管内皮生长因子及受体、血管生成素及受体的药物可阻断异位病灶的血管形成,可能成为治疗Ems的重要手段之一。     

多层螺旋CT血管成像在脑动静脉畸形诊断及治疗中的价值

目的探讨脑动静脉畸形（CAVM）在多层螺旋cT血管造影（MSCTA）中的表现及MSCTA的临床价值。方法收集36例行MSCTA检查的CAVM患者的资料,采用容积再现重组（VR）血管生长技术（AV）进行血管重建,分析供血动脉、引流静脉的表现。结果36例CAVM患者中,病变累及枕叶10例,颞叶9例,额叶2例,顶叶3例,枕叶、小脑半球7例,颞、枕叶3例,额、顶叶2例,均清楚显示畸形血管团、供血动脉及引流静脉;4例合并血管畸形内动脉瘤,2例合并血管畸形外动脉瘤,3例蛛网膜下腔出血,6例脑出血。结论MSCTA能清楚显示CAVM的畸形血管团、供血动脉、引流静脉及合并的动脉瘤。     

Targeting the angiopoietin (Ang)/Tie-2 pathway in the crosstalk between acute myeloid leukaemia and endothelial cells: studies of Tie-2 blocking antibodies,exogenous Ang-2 and inhibition of constitutive agonistic Ang-1 release

Background: The Tie-2 receptor can bind its agonistic ligand Angiopoietin-1 (Ang-1) and the potential antagonist Ang-2. Tie-2 can be expressed both by primary human acute myeloid leukaemia (AML) cells and endothelial cells, and Tie-2-blocking antibodies are now being evaluated in clinical trials for cancer treatment. Design and methods: We investigated the effects of Tie-2-blocking antibodies, exogenous Ang-2 and pharmacological agents on AML cell proliferation and the release of angioregulatory mediators. Results: Tie-2-blocking antibodies had a growth inhibitory effect on human AML cells co-cultured with microvascular endothelial cells, but this inhibition was not observed when leukaemic cells were co-cultured with fibroblasts or osteoblasts. AML cell viability in co-cultures was not altered by anti-Tie-2. Furthermore, anti-Tie-2 decreased hepatocyte growth factor (HGF) levels and increased CXCL8 levels in co-cultures, whereas the levels of endocan (a proteoglycan released by endothelial cells) were not altered. The only significant effects of exogenous Ang-2 were decreased levels of HGF and endocan. Constitutive AML cell release of agonistic Ang-1 was decreased by the proteasomal inhibitor bortezomib and the specific IκB-kinase/NFκB inhibitor BMS-345541. Conclusion: We conclude that various strategies for inhibition of Tie-2-mediated signalling should be considered in AML therapy, possibly in combination with other antiangiogenic strategies.     

Angiotensin II (Ang II) evoked secretion of the human placental lactogen (HPL) in intrauterine growth retardation: examination of the relationship with Ang II receptor type 1 (AT1) expression

Angiotensin II (Ang II) and its hemodynamic effects on placental vasculature mediated via Ang II receptor type 1 (AT1) may play significant role in intrauterine growth retardation (IUGR). Placental lactogen (HPL) production directly reflects placental function. We compared influence of Ang II on HPL production in normal and IUGR-complicated pregnancies and correlated this phenomenon with AT1 expression. Basal and Ang II-evoked HPL secretion was examined in perfused placental lobules using ELISA. After immunostaining of placental sections, AT1 expression was estimated using quantitative morphometry. Ang II increased HPL secretion. Ang II-evoked increase in HPL concentration in the perfusion fluid was 27.36+/-6.4 (%, +/-SEM) lower in IUGR (p<0.05) compared to normal-course pregnancies. AT1 expression was significantly decreased in IUGR and was 78.12+/-8.2 (%, +/-SEM) of the mean value of controls. Demonstrating that Ang II-evoked secretion of HPL in preeclampsia-free IUGR is decreased and correlates with down-regulated expression of AT1, we present a new approach to the pathophysiology of IUGR.     

4,5-Epoxy-2(E)-decenal-induced formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine adducts

trans-4,5-Epoxy-2(E)-decenal reacted with 2'-deoxyadenosine to give 1,N(6)-etheno-2'-deoxyadenosine as well as other 2'-deoxyadenosine adducts. It also reacted with 2'-deoxyguanosine to give 1,N(2)-etheno-2'-deoxyguanosine and other 2'-deoxyguanosine adducts. Synthetic trans-4,5-epoxy-2(E)-decenal was quite stable under the reaction conditions that were used. It was not contaminated with 2,3-epoxyoctanal, a potential precursor to the formation of unsubstituted etheno adducts. Furthermore, using a sensitive LC/MS assay, it was possible to show that no 2,3-epoxyoctanal was formed during prolonged incubations of trans-4,5-epoxy-2(E)-decenal. Therefore, trans-4,5-epoxy-2(E)-decenal, a primary product of lipid peroxidation, is a precursor to the formation of 1,N(6)-etheno-2'-deoxyadenosine and 1,N(2)-etheno-2'-deoxyguanosine. There is no need for an additional oxidation step such as would be required if trans,trans-2,4-decadienal or 4-hydroxy-2-nonenal were the lipid hydroperoxide decomposition products that initiated the formation of unsubstituted etheno adducts. These findings provide an important link between a primary product of lipid peroxidation and a mutagenic DNA lesion that has been detected in human tissues.     

1—（1H—1，2，4—三唑—1—基）—2—（2，4—二氟苯基）—3—取代—2—丙醇的合成及抗真菌活性研究（Ⅱ）

基于计算机辅助药物设计系统及靶酶模建的需要。根据氮唑类抗真菌药物的构效关系和作用机理。设计合成了15个1-（1H-1,2,4-三唑-1-基）-2-（2,4-二氟苯基）-3-取代-2-丙醇类化合物,均为首次报道。运用微量注偌倍比稀释法对8种常见致病真菌进行外抑菌试验。化合物Ⅳg具有较强的体外抗真菌活性。     

血管生成素样蛋白1和2水平在急性心肌梗死患者中的表达及临床意义

目的 探讨血管生成素样蛋白1（Ang-1）和血管生成素样蛋白2（Ang-2水平）在急性心肌梗死（AMI）患者中的表达以及与肌钙蛋白T（cTnT）的相关性.方法 选取AMI患者75例,同期选择健康体检者50例为对照组,采用酶联免疫吸附试验（ELISA）和化学发光法分别检测研究对象中Ang-1、Ang-2和cTnT水平,并与对照组作比较.结果 AMI患者Ang-2、Ang-2/Ang-1水平分别为（2310.2±131.6） ng/L和（11.9±1.3）,显著高于对照组的（905.8±171.4） ng/L和（4.6±1.8）,差异有统计学意义（P＜ 0.05）;AMI患者Ang-1水平为（19 589.3±2033.4） ng/L,对照组为（19 612.1±1824.1） ng/L,差异无统计学意义（P＞0.05）.Ang-2水平和Ang-2/Ang-1与cTnT均呈正相关（r=0.597,0.604,P＜0.05）.结论 高Ang-2水平和Ang-2/Ang-1是心肌梗死的危险因素,并与cTnT正相关.     

含哌嗪环的三唑醇类化合物的合成及体外抗真菌活性

目的设计合成含哌嗪环侧链的三唑醇类化合物并研究其体外抗真菌活性。方法以2-氯-2′,4′-二氟苯乙酮为起始原料经多步反应合成目标化合物，化合物结构经IR、^1H-NMR谱确证；选择8种真菌为实验菌株，按国际标准抗真菌敏感性实验方法测定体外抑菌活性。结果设计合成了11个新化合物。所有目标化合物对8种真菌均具有一定的抑制作用。结论多个目标化合物的抗真菌活性明显高于阳性对照药氟康唑，其中化合物11具有广谱、高活性的优点，其体外抗真菌活性与对照药伊曲康唑相当，有进一步研究开发的价值。     

Multiple column peptide synthesis,Part 2 (1, 2)

A manually operated apparatus for parallel multiple column soli-phase peptide synthesis is described. It employs Fmoc-amino acid-O-Dhbt or -Pfp esters in the continuous flow version of the polyamide method on small packed columns of kieselguhr supported resin in a reaction block of Teflon. The solvents and deprotecting reagents are dispensed from two washers in a parallel fashion and reagent consumption is low. Activated and protected amino acids are transferred from a dispenser tray as solutions, eight at a time. The use of the method is demonstrated by the synthesis of overlapping peptides from a protein structure and of analogous protease substrates. The products have been characterized by HPLC, FAB mass spectroscopy and amino acid analysis.     

H2-Antihistaminika, 15. Mitt.1) 1,n-Bis(2-imidazolyl)alkane

H₂-Antihistaminics, XV: 1,n-Bis(2-imidazolyl)alkanes 1,n-Bis(2-imidazolyl)alkanes with histamine H₂-functional side-chains at C-4 of the imidazole rings were prepared and tested for H₂-antihistaminic activity.     

含氧叔丁基三唑醇类化合物的合成及其体外抗真菌活性

目的设计合成含氧取代的叔丁基三唑醇类化合物并研究其体外抗真菌活性。方法以一氯频那酮为起始原料经多步反应合成目标化合物,化合物结构经1H-NMR谱、IR谱确证;选择8种真菌为实验菌株,按国际标准抗真菌敏感性实验方法测定体外抑菌活性。结果与结论合成了12个新化合物。所有目标化合物对8种真菌均具有一定的抑制作用。可以将现有的三唑醇类抗真菌药物结构中的2,4-二氟苯基替换成其他疏水性基团来设计抗真菌化合物。