E-钙黏蛋白和nm23-H1在卵巢上皮性癌中的表达及临床意义

目的 上皮性钙黏蛋白(E-cad)和nm23-H1在卵巢上皮性癌中的表达及其与卵巢癌侵袭转移的关系.方法 采用免疫组化SP法检测33例卵巢上皮性癌,20例卵巢良性上皮性肿瘤和10例卵巢正常组织中E-cad和nm23-H1的表达.结果 E-cad在卵巢癌组织中的阳性表达率(54.5％)明显低于正常组(100.0％)及良性组(65.0％)(P均＜0.05);nm23-H1在卵巢癌组织中的阳性表达率(66.7％)明显低于正常组(90.0％)及良性组( 85.0％)(P均＜0.05);E-cad和nm23-H1的阳性表达与卵巢癌临床分期、组织分级和淋巴转移有关(P＜0.05);在卵巢癌组织中E-cad与nm23-H1呈正相关关系.结论 E-cad及nm23-H1与卵巢癌的发生、发展和侵袭转移有关,是评估预后的有效指标;E-cad与nm23-H1在卵巢癌中表达呈正相关,在卵巢癌发生发展中可能存在协同效应.     

上皮性卵巢癌中基质金属蛋白酶-2及其抑制剂的表达及意义分析

目的检测上皮性卵巢癌中基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及金属蛋白酶组织抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)的表达水平,并分析其临床意义。方法采用免疫组化染色法检测MMP-2、TIMP-2在上皮性卵巢癌、上皮性良性卵巢肿瘤及正常卵巢组织3组对象卵巢组织中的阳性表达率,分析上皮性卵巢癌患者不同临床病理特征下MMP-2及TIMP-2的阳性表达水平。结果上皮性卵巢癌组卵巢组织MMP-2及TIMP-2的阳性表达率明显高于良性上皮性卵巢肿瘤组和正常卵巢组织组(P0.05)。MMP-2及TIMP-2在上皮性卵巢癌Ⅲ期+Ⅳ期患者中的阳性表达率明显高于Ⅰ期+Ⅱ期患者(P0.05);在低分化(G3)患者中的阳性表达率明显高于高、中分化(G1+G2)患者(P0.05);在有淋巴结转移患者中的阳性表达率明显高于无淋巴结转移患者(P0.05)。结论 MMP-2和TIMP-2的检测是否可作为早期诊断上皮性卵巢癌的生物指标,尚需进一步研究,但MMP-2及TIMP-2的表达水平与上皮性卵巢癌的临床分期、分化程度、淋巴结转移有关,可作为判断上皮性卵巢癌预后的辅助指标。     

卵巢上皮性肿瘤中WT1与Ki67的表达及其临床意义

目的:探讨肾母细胞瘤基因(Wilm's tumor gene,WT1)和Ki67在卵巢上皮性肿瘤中的表达、临床意义及二者的相关性。方法:采用免疫组化SP法检测40例恶性卵巢上皮性肿瘤组织(恶性组)、30例良性卵巢上皮性肿瘤组织(良性组)和20例正常卵巢组织(正常组)中WT1和Ki67的表达。结果:上皮性卵巢癌与卵巢良性肿瘤、正常卵巢组织相比,WT1和Ki67阳性表达率都增加,差异有统计学意义(P0.05)。WT1阳性表达与上皮性卵巢癌的病理分级及FIGO分期相关(P0.05),而与年龄、淋巴结转移和病理类型无关(P0.05)。Ki67阳性表达与上皮性卵巢癌FIGO分期和病理分级相关(P0.05),与淋巴结转移、年龄和病理类型无关(P0.05)。在上皮性卵巢癌中,WT1和Ki67阳性表达呈正相关(r=0.765,P0.05)。结论:WT1异常高表达可能是诊断卵巢癌的分子标志物。WT1和Ki67共同参与上皮性卵巢癌的肿瘤细胞的过度增殖,二者结合检测对恶性卵巢肿瘤的临床诊断和治疗有一定价值。     

Survivin在上皮性卵巢癌中的表达及意义

目的:检测survivin在上皮性卵巢癌组织中的表达,探讨survivin的表达与上皮性卵巢癌临床病理特征的关系。方法:应用免疫组织化学链霉亲和素-生物素-过氧化物霉复合物(SABC)方法,检测40例上皮性卵巢癌组织,20例良性上皮性卵巢肿瘤组织,20例正常卵巢组织中survivin的表达情况。结果:上皮性卵巢癌组织中survivin的阳性表达率为77.5%,高于良性上皮性卵巢肿瘤组织及正常卵巢组织的10%～0%(P<0.05),与组织学类型无相关性(P>0.05),与临床分期、组织学分级及淋巴结转移有关(P<0.05)。结论:survivin在上皮性卵巢癌组织中皆呈高表达,提示survivin可能与上皮性卵巢癌的浸润、转移有关。     

Activin在上皮性卵巢癌中的表达及意义

目的:检测activin在上皮性卵巢癌组织中的表达,探讨activin的表达与上皮性卵巢癌临床病理特征的关系。方法:应用免疫组织化学链霉亲和素-生物素-过氧化物霉复合物(SABC)方法,检测40例上皮性卵巢癌组织,20例良性上皮性卵巢肿瘤组织,20例正常卵巢组织中activin的表达情况。结果:上皮性卵巢癌组织中activin的阳性表达率为67.5%,高于良性上皮性卵巢肿瘤组织及正常卵巢组织的25%及10%(P<0.05),与组织学类型、临床分期无相关性(P>0.05),与组织学分级及淋巴结转移有关(P<0.05)。结论:Activin在上皮性卵巢癌组织中皆呈高表达,提示activin可能与上皮性卵巢癌的浸润、转移有关。     

E-钙黏附素和β-连环素在上皮性卵巢肿瘤中的表达及意义

目的探讨上皮钙黏附素(E-cadherin,E-cad)和β-连环素(β-catenin,β-cat)在上皮性卵巢肿瘤中的表达及意义。方法应用免疫组化S-P法检测10例正常卵巢组织、10例良性肿瘤、40例上皮性卵巢癌(epithelial ovarian carcinoma,EOC)中E-cad与β-cat的表达。结果E-cad、β-cat在正常卵巢组织中正常表达,在良性卵巢肿瘤中异常表达率分别为20.0%,10.0%。在上皮性卵巢癌中异常表达显著增高,分别为72.5%、100%,卵巢癌中的异常表达率显著高于卵巢正常组织及良性肿瘤,差异有显著意义(P<0.05)。随着卵巢癌的病理分级增加,异常表达逐渐提高,在G1-G2,G3(P<0.05),在I期～Ⅱ、Ⅲ、Ⅳ期(P<0.05),有淋巴结转移的异常表达率明显高于无淋巴节转移组(P<0.05)。结论E-cad与β-cat的异常表达与上皮性卵巢癌的发生、发展有关,并与卵巢癌的临床生物特性有一定关系。     

MMP-9在卵巢上皮性肿瘤中的表达和微血管密度与临床病理的关系

[目的]了解MMP-9和微血管密度(MVD)在卵巢上皮性肿瘤中的表达情况,探讨MMP-9和MVD与卵巢癌局部侵袭、淋巴结转移情况以及肿瘤细胞的分化程度的关系.[方法]收集卵巢恶性上皮性肿瘤组织50例,15例卵巢良性上皮性肿瘤和5例正常卵巢组织作为对照.采用免疫组织化学的方法进行定性分析.[结果]MMP-9的阳性表达率在卵巢癌组织中增高,达70%. MMP-9表达情况与肿瘤的临床分期、分化程度及淋巴结的转移情况有关.分别在进展晚期(89.3%)、低分化(81.8%)和有淋巴系统转移的组织中阳性率增高(93.8%).MVD与MMP-9表达成正相关.[结论]卵巢癌中MMP-9和MVD的阳性表达率增高,MMP-9在卵巢癌局部侵袭和淋巴结转移过程中有促进作用,MMP-9和MVD与卵巢癌的分化程度有关.     

EGFR及MVD在卵巢上皮性肿瘤中的表达及意义

[目的]研究表皮生长因子受体(EGFR)及微血管密度(MVD)在卵巢上皮性肿瘤中的表达及意义.[方法]应用免疫组织化学SP法检测90例卵巢癌组织,30例交界性卵巢肿瘤组织,15例卵巢良性肿瘤组织和5例正常卵巢组织中EGFR及MVD的表达. [结果]在卵巢癌中的EGFR阳性表达率和MVD值分别为50%和20.59±5.44,显著高于良性卵巢肿瘤和正常卵巢组织的34%和7.21±3.84(P(0.05),且与肿瘤的临床分期、分化程度及淋巴结的转移有关.在卵巢癌组织中EGFR与MVD的表达呈正相关(r=0.500 2,P<0.01). [结论]EGFR及MVD有可能在卵巢上皮性肿瘤的侵袭和转移中起重要作用,可作为判断卵巢上皮性肿瘤恶性程度和预后的一个良好指标.     

Survivin蛋白和VEGF在上皮性卵巢癌中的表达及相关性

目的:探讨Survivin蛋白和VEGF在上皮性卵巢癌组织中的表达及其在上皮性卵巢癌发生、发展中的作用及两者的相关性。方法:采用链霉菌抗生物素蛋白-过氧化酶(SP)免疫组织化学方法检测45例上皮性卵巢癌、19例卵巢良性上皮性肿瘤及16例正常卵巢组织中Survivin和VEGF的表达,并分析其与各临床病理特征的关系及两者的相关性。结果:①上皮性卵巢癌中Survivin蛋白和VEGF表达水平均显著高于卵巢良性上皮性肿瘤及正常卵巢组织,差异有显著性(P<0.05)。②Sur-vivin蛋白和VEGF的阳性表达率与上皮性卵巢癌病理类型无关(P>0.05),与临床分期、组织学分级及淋巴结转移有关(P<0.05)。③上皮性卵巢癌中Survivin蛋白与VEGF的表达呈正相关。结论:Survivin蛋白和VEGF均可作为反映上皮性卵巢癌生物学行为的客观参考指标,与卵巢癌的发生、发展和转移密切相关,Survivin和VEGF的联合检测有助于判断卵巢癌的恶性程度和预后,同时为卵巢癌的靶向治疗提供新的途径。     

MMP-9、Ⅳ型胶原、CD34在卵巢上皮癌临床分期中的表达及意义

目的:探讨基质金属蛋白酶9(MMP-9)、Ⅳ型胶原、CD34在不同期别卵巢上皮癌中的表达及意义。方法:选取广州医学院第三附属医院2003～2006年住院卵巢肿瘤患者82例(卵巢恶性上皮性肿瘤48例,卵巢交界性上皮性肿瘤23例,卵巢良性上皮性肿瘤11例),采用免疫组化Elivision法,检测MMP-9、Ⅳ型胶原和CD34在肿瘤组织中的表达情况。结果:MMP-9的表达在卵巢癌晚期(Ⅲ～Ⅳ期)组与卵巢癌早期(Ⅰ～Ⅱ期)组间差异存在统计学意义(F=21.306,P0.001)。CD34在卵巢癌晚期组与卵巢癌早期组间的表达差异也有统计学意义(F=90.632,P0.001)。Ⅳ型胶原的表达在卵巢癌晚期组与卵巢癌早期组间比较差异有统计学意义(F=10.132,P0.001)。随着临床分期的增高,MMP-9和CD34的阳性表达及Ⅳ型胶原的缺失表达越明显。CD34的表达与MMP-9的阳性表达呈正相关(rs=0.802,P=0.000 1)。MMP-9的阳性表达与Ⅳ型胶原的缺失表达呈正相关(rs=0.796,P0.000 1)。MMP-9在有淋巴结转移组的表达高于无淋巴结转移组的表达(Z=-3.171,P=0.002)。CD34在有淋巴结转移组的表达高于无淋巴结转移组的表达(t=-4.187,P0.001)。结论:MMP-9、CD34的阳性表达及Ⅳ型胶原的缺失表达与卵巢癌的临床分期及转移有关。通过联合检测MMP-9、CD34、Ⅳ型胶原在卵巢癌的表达对判断卵巢癌的预后具有重要的临床意义。     

Squalene-adjuvanted H7N9 virus vaccine induces robust humoral immune response against H7N9 and H7N7 viruses

Recent cases of avian influenza H7N9 have caused great concerns that virus may become transmittable between humans. It is imperative to develop an effective vaccine to fight against the pandemic potential of this H7N9 influenza virus to protect human from the disease. This study aims to investigate an optimized formulation for the development of H7N9 vaccines. Various doses of H7N9 inactivated whole or split-virus antigens (0.5, 1.5, or 3 μg based on hemagglutinin content) combined with squalene-based adjuvant (AddaVAX), aluminum hydroxide Al(OH)₃ or without adjuvant were evaluated for the efficacy of H7N9 vaccine regiments in mice. With either H7N9 whole or split-virus based vaccines, AddaVAX-adjuvanted formulations were the most immunogenic in eliciting significant humoral immune response against H7N9 virus and exhibited strong cross-reactive response in hemagglutination inhibition (HAI) and viral-neutralization assays against H7N7 virus as well. In contrast, formulations with Al(OH)₃ or without adjuvant were less immunogenic and elicited lower titers of HAI and microneutralization assays against both viruses. Dose-sparing experiments suggested that the formulation with as low as 0.004 μg of split or whole virus vaccine antigens together with 50% AddaVAX provided sufficient sero-protective HAI titers and achieved essential virus-neutralizing antibody titers against H7-subtype influenza viruses in mice. Protection experiments demonstrated that the formulation of 0.004 μg to 0.5 μg of split-virion vaccines with AddaVAX conferred full protection against viral challenge up to 100 LD50 of wild-type H7N9 virus, with 0% survival in placebo group. Taken together, our study demonstrates that squalene-based adjuvant can significantly enhance the protective efficacy of H7N9 virus vaccine and provides a useful strategy to confront the potential pandemic outbreaks of H7N9 virus.     

全国中医药工作会议七道难题七个解法--中药现代化面临破题

记者在2005年全国中医药工作会议上获悉,国家中医药管理局日前完成的一项调查表明,我国中药现代化发展仍面临七大难题.这七大难题是:     

小檗胺下调MCF7及MCF7/ADR细胞Suivivin表达

目的探讨钙调蛋白拮抗剂小檗胺(BBM)下调抗凋亡基因Survivin表达的可能性。方法采用人乳腺癌细胞MCF7及其耐阿霉素(ADR)MCF7/ADR细胞与不同浓度BBM培养72h后,采用半定量RT-PCR法检测SurvivinmRNA表达。结果20μmol/LBBM使MCF7和MCF7/ADR细胞SurvivinmRNA表达分别由0.43±0.02下降至0.21±0.04和0.57±0.05下降至0.45±0.04(P值均<0.01)。结论BBM可下调MCF7和MCF7/ADR细胞SurvivinmRNA表达。     

Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine

Background

H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV).

Methods

Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04 (H7N3) pLAIV all given as 10^7.5 50% tissue culture infective doses (TCID₅₀) intranasally. A subset of subjects received one 45 μg dose of H7N7 pIIV containing the A/Mallard/Netherlands/12/2000 HA intramuscularly 18–24 months after pLAIV. Viral shedding was assessed by culture and real-time polymerase chain reaction (rRT-PCR), B cell responses following pLAIV were evaluated by ELISPOT and flow cytometry. Serum antibody was assessed by hemagglutination-inhibition (HAI), microneutralization (MN) and ELISA assays after each vaccine.

Results

Serum HAI or MN responses were not detected in any subject following one or two doses of either H7 pLAIV, although some subjects had detectable H7 specific B cells after vaccination. However, 10/13 subjects primed with two doses of H7N7 pLAIV responded to a subsequent dose of the homologous H7N7 pIIV with high titer HAI and MN antibody that cross-reacted with both North American and Eurasian lineage H7 viruses, including H7N9. In contrast, naïve subjects and recipients of a single dose of the mismatched H7N3 pLAIV did not develop HAI or MN antibody after pIIV.

Conclusions

While pLAIVs did not elicit detectable serum MN or HAI antibody, strain-specific pLAIV priming established long term immune memory that was cross-reactive with other H7 influenza strains. Understanding the mechanisms underlying priming by pLAIV may aid in pandemic vaccine development.     

Safety and immunogenicity of an 8 year interval heterologous prime-boost influenza A/H7N7-H7N9 vaccination

Background

Influenza A/H7N9 viruses are undergoing antigenic drift since their emergence in 2013, and vaccination strategies are needed for pandemic preparedness. Two doses of adjuvanted monovalent inactivated influenza A/H7N9 vaccine (IIV1 A/H7N9) are needed for optimal serological responses. However, administering 2 doses in a pandemic setting might be challenging. We evaluated the immunogenicity of “boosting” with IIV1 A/H7N9 in subjects “primed” 8?years previously with IIV1 A/H7N7.