Th1/Th2类细胞因子与葡萄胎恶变的相关性研究

目的:通过对妊娠滋养细胞疾病患者外周血血清中Th1/Th2类细胞因子的测定,从免疫学角度探讨Th1/Th2类细胞因子预测葡萄胎恶变的价值。方法:收集1997至2001年首次以葡萄胎诊断进行清宫和手术的患者的外周血血清,采用酶联免疫吸附法检测血清中IFN-γ、IL-2、IL-4、IL-10的水平来确定Th1/Th2的活性。结果:与侵葡+绒癌组相比,葡萄胎组IFN-γ含量明显增加(P<0.001),IL-10含量明显降低(P<0.001)。葡萄胎患者中,与非恶变组相比,恶变组Th1类细胞因子(IFN-γ,IL-2)含量呈下降趋势,而Th2类细胞因子(IL-4,IL-10)含量呈增加趋势,4种细胞因子变化均具有统计学差异(P<0.0001)。随着滋养细胞增生程度的增加,4种细胞因子的变化均具有统计学差异,除外IL-4的变化在轻、中度增生组中无统计学意义(P>0.05)。结论:Th1/Th2细胞因子向Th2漂移时,葡萄胎恶变倾向增高。     

卵巢癌患者血浆中Th1/Th2类细胞因子的检测

探讨卵巢癌患者血浆中Th1/Th2类细胞因子失调及其临床意义。方法 :用ELISA法检测了 2 5例卵巢癌及 15例健康妇女血浆中IL - 2、IFN -γ、IL - 6和IL - 10水平。结果 :卵巢癌患者较健康妇女血浆中IL - 2水平明显降低 ,而IL - 6和IL - 10明显升高 ,且这种变化随临床期别的升高更加明显。结论 :卵巢癌患者外周血中Th1/Th2类细胞因子失调 ,在卵巢癌的发生发展中可能起重要作用。     

Th1／Th2型细胞因子与妊娠高血压综合征

主要由Th1细胞分泌促进细胞免疫的Th1型细胞因子和主要由Th2细胞分泌促进体液免疫的Th2型细胞因子在妊娠时期母胎间细胞因子网络平衡的调控中有重要作用，就Th1/Th2型细胞因子在妊娠高血压综合征中的作用与机制做了大量的研究，发现存在着两种因子的失衡。     

Th1/rh2型细胞因子与妊娠高血压综合征

主要由Th1细胞分泌促进细胞免疫的Th1型细胞因子和主要由Th2细胞分泌促进体液免疫的Th2型细胞因子在妊娠时期母胎间细胞因子网络平衡的调控中有重要作用。近年，就Th1／Th2型细胞因子在妊娠高血压综合征中的作用与机制做了大量的研究，发现存在着两种因子的失衡。     

Th1/rh2型细胞因子与妊娠高血压综合征

主要由Th1细胞分泌促进细胞免疫的Th1型细胞因子和主要由Th2细胞分泌促进体液免疫的Th2型细胞因子在妊娠时期母胎间细胞因子网络平衡的调控中有重要作用。近年，就Th1／Th2型细胞因子在妊娠高血压综合征中的作用与机制做了大量的研究，发现存在着两种因子的失衡。     

Th1、Th2型细胞因子与妊娠及其并发症的关系

免疫耐受(immune tolerance)是机体免疫系统在接触抗原后产生的特异性免疫无反应状态。妊娠期母体对同种半异体的胎儿表现为免疫耐受，过去普遍认为这是孕妇免疫系统受抑制的结果，但近年来越来越多的研究表明这是一个免疫调节过程。妊娠期母体通过复杂的激素一免疫一细胞因子网络对妊娠的各个生理过程，包括着床、胚胎生长发育以及分娩过程进行免疫调节，而T辅助细胞亚群(Thl、Th2细胞)及其分泌的细胞因子在这一过程中起核心调控作用。现将Thl、Th2型细胞因子的来源及其与妊娠的关系作一综述。     

hnRNP E1对妊娠滋养细胞疾病恶变的早期预测价值评估

目的:通过分析hnRNP E1蛋白在良性及恶变转归葡萄胎中的表达,评估其在妊娠滋养细胞疾病恶变中的预测价值.方法:选取2007年至2008年因葡萄胎在南京市妇幼保健院清宫的40例患者,收集葡萄胎清宫标本.根据患者5年内的预后情况将早期清宫标本分为:良性转归组(29例)和恶性转归组(11例).放射免疫法测定清宫前血清β-HCG水平,免疫组化法检测葡萄胎组织中hnRNP E1蛋白的表达及分布情况,RT-PCR检测葡萄胎组织中hnRNP El mRNA的表达,Western blot法检测葡萄胎组织中hnRNP E1蛋白的定量表达.结果:hnRNP E1蛋白在葡萄胎组织中主要表达于滋养细胞的细胞核及细胞质中.恶性转归组葡萄胎组织中的hnRNP El mRNA和蛋白相对表达水平分别为(0.49±0.18,0.89±0.24),均显著低于良性转归组(1.15±0.24,1.61±0.31) (P＜0.05).hnRNP E1表达与葡萄胎恶变及血清β-HCG水平呈负相关(P＜0.05).结论:hnRNP E1表达下调可能是滋养细胞疾病恶性转化的早期事件.hnRNP E1有望成为预测葡萄胎恶变的新靶标之一,为临床预防性化疗提供有力的理论依据.     

Fas／FasL与滋养细胞及妊娠滋养细胞疾病关系的研究

Fas／FasL是凋亡信号传导的一条途径。正常妊娠滋养细胞表达FasL诱导母体活化淋巴细胞凋亡是胎儿免疫耐受的重要机制。Fas／FasL在妊娠滋养细胞疾病中表达的研究刚起步。葡萄胎滋养细胞表达FasL引起蜕膜Fas巴细胞凋亡促进免疫耐受和滋养细胞的存活。恶性滋养细胞Fas介导的凋亡敏感性降低及与FasL同时表达反击淋巴细胞可传授免疫赦免。Fas／FasL可能代表一个机制，通过这个机制恶性滋养细胞抵抗凋亡，逃避免疫监视和发生转移。     

T辅助细胞1、2细胞因子平衡与正常妊娠及习惯性流产关系的初步探讨

目的　探讨T辅助细胞 1(Th1)细胞因子 (γ干扰素、肿瘤坏死因子α)、Th2细胞因子 (白细胞介素 4、白细胞介素 10 )平衡在母胎免疫耐受中的作用机理。方法　用半定量逆转录 聚合酶链反应 (RT PCR)技术 ,检测 11例正常未妊娠妇女、10例正常早期妊娠妇女、11例正常晚期妊娠妇女、11例习惯性流产患者的外周血单个核细胞内γ干扰素、肿瘤坏死因子α、白细胞介素 4、10mRNA表达水平的相对含量 (% )。结果　 (1)白细胞介素 10 :正常未妊娠妇女为 (13.5 8± 3.91) % ,正常早期妊娠妇女为 (18.6 1± 5 .43) % ,正常晚期妊娠妇女为 (2 0 .72± 5 .36 ) % ,习惯性流产妇女为 (9.48± 2 .84) % ,后者明显低于前 3者 (P <0 .0 5 )。 (2 )γ干扰素 :正常未妊娠妇女为 (30 .76± 5 .35 ) % ,正常早期妊娠妇女为 (2 7.2 3± 5 .74) % ,正常晚期妊娠妇女为 (2 4.6 8± 5 .5 5 ) % ,习惯性流产妇女为 (36 .0 8± 5 .75 ) % ,后者明显高于前 3者 (P <0 .0 1)。 (3)肿瘤坏死因子a水平在以上 4种妇女之间比较 ,差异无显著性 (P >0 .0 5 )。结论　正常妊娠是以分泌Th2细胞因子为主的 ,当发生偏向性地分泌炎性Th1细胞因子时 ,可能会导致习惯性流产的发生 ,提示Th1与Th2细胞因子平衡在母胎免疫耐受中起一定作用。     

Assessment of Her-2/neu expression in hydatidiform moles for prediction of subsequent gestational trophoblastic neoplasia

OBJECTIVE: The aim of the present study was to asses the ability of Her-2/neu immunohistochemical staining of the molar tissue to predict the risk of developing gestational trophoblastic neoplasia (GTN). METHODS: Sections prepared from 33 consecutive formalin-fixed paraffin-embedded archival reconfirmed hydatidiform mole tissue blocks were immunohistochemically stained for Her-2/neu. The staining was scored according to the subjectively evaluated intensity of staining and the proportion of stained villous cytotrophoblastic cells. Clinical data were abstracted from medical files. RESULTS: 23 patients had a complete and 10 a partial mole. Nine patients (27.3%) were diagnosed with GTN [7 of 23 patients with a complete mole (30.4%) and 2 of the 10 (20.0%) with a partial mole]. A positive immunohistochemical Her-2/neu stain was found in 6 (18.2%) of the patients with hydatidiform mole (3 with a complete mole). The rate of Her-2/neu expression was somewhat higher in moles with subsequent GTN than in moles with an uneventful course (22.2% vs. 16.6%, respectively). The difference did not reach significance (Fisher's Exact Test, P=0.55) possibly due to the small number of cases (power of <5%). The sensitivity and specificity of Her-2/neu expression for prediction of GTN was 22.2% and 83.3%, respectively, and the positive and negative predictive value 33.3% and 74.1%, respectively. CONCLUSION: While the specificity of Her-2/neu immunohistochemical staining for prediction of GTN is relatively high, the low sensitivity and low positive and negative predictive value precludes its practical clinical use for prediction of post-molar GTN. The quest for a precise predictor of post-molar GTN should continue.     

癌基因、妊娠性滋养细胞增生与葡萄胎恶变关系的研究

目的：探讨癌基因、妊娠性滋养细胞增生程度与葡萄胎恶变的关系。方法：采用针对Ｃ－Ｈａ－ｒａｓ及Ｃ－ｅｒｂＢ２基因表达产物Ｐ２１和Ｐ１８５的单克隆抗体进行免疫组织化学染色。检测８２例葡萄胎中两种基因产物的表达情况，经２年以上随访证实未发生恶变３２例为非恶变组，经手术和临床证实发生恶变５０例为恶变组，其中３５例行手术治疗。结果：恶变组Ｐ２１的表达程度低于非恶变组（Ｐ＝０．００８２）；Ｐ１８５的表达显著高于非恶变组（Ｐ＝０．００２８）。手术治疗的３５例中，恶变后两种基因产物的表达改变较恶变前更明显。两组葡萄胎中滋养细胞增生程度差异无显著性（Ｐ＝０．４１３）。不同来源的绒毛膜癌（绒癌）之间及绒癌与侵蚀性葡萄胎（侵葡）之间，Ｐ２１和Ｐ１８５的表达差异亦无显著性（Ｐ＝０．２６８，Ｐ＝０．７１９）。结论：Ｐ２１的低表达及Ｐ１８５的高表达与葡萄胎恶变有关，但与其恶性转化方向无关；滋养细胞增生程度与葡萄胎恶变亦无关。     

主动免疫治疗对不明原因习惯性流产患者辅助T细胞因子水平的影响

目的　探讨主动免疫治疗对不明原因习惯性流产 (UHA)患者辅助T细胞 (Th) 1 /Th2型细胞因子水平的影响。方法　采用酶联免疫吸附法 ,检测 30例半年内接受过淋巴细胞主动免疫治疗的UHA患者 (治疗组 ) ,及 2 5例未经治疗的UHA患者 (未治疗组 ) ,外周血单个核细胞 (PBMC)经滋养细胞抗原刺激产生的Th1型细胞因子白细胞介素 (IL) 2、γ干扰素 (IFN γ)及Th2型细胞因子产生IL 4、IL 1 0水平。并选取 1 5例正常非妊娠妇女作为对照 (对照组 )。结果　 (1 )在最佳诱导时间内 ,治疗组IL 2、IFN γ的水平分别为 (1 0 8± 37)ng/L、(1 1 0± 52 )ng/L ,明显低于未治疗组的 (2 2 3± 85)ng/L、(32 6±92 )ng/L(P值均 <0 .0 5) ;IL 4、IL 1 0水平分别为 (50± 1 1 )ng/L、(1 4 0± 37)ng/L ,明显高于未治疗组的(2 3± 1 1 )ng/L、(52± 2 8)ng/L(P值均 <0 .0 5)。未治疗组IL 2、IFN γ水平明显高于对照组的 (92± 32 )ng/L、(1 0 2± 35)ng/L(P值均 <0 .0 5) ;IL 4、IL 1 0水平低于对照组的 (62± 2 1 )ng/L、(1 50± 42 )ng/L(P值均 <0 .0 5)。治疗组与对照组各细胞因子水平比较 ,差异均无显著性 (P值均 >0 .0 5)。 (2 )治疗组30例患者治疗后半年内妊娠 2 6例 ,其中 8例自然流产 ,IL 2、IFN γ水平明显高于 1 8例妊娠     

Increase in the incidence of gestational trophoblastic disease in The Netherlands

Objective

The objective of this study is to determine the incidence and time trends of gestational trophoblastic disease (GTD) in The Netherlands using population-based data.

Methods

Data on patients with a pathologically confirmed diagnosis of GTD from 1995 to 2008 were obtained from PALGA, a national archive containing all histopathology reports in The Netherlands. Data on number of deliveries were obtained from the Database of Statistics Netherlands.

Results

During the study period, 4249 GTD patients were registered. Overall incidence rates of hydatidiform mole (HM), choriocarcinoma and placental site trophoblastic tumor (PSTT) were 1.34 per 1000 deliveries, 3.1 per 100,000 deliveries, and 1.0 per 100,000 deliveries, respectively. Incidence rates of HM increased from 1.02 per 1000 deliveries in 1995 to 1.56 per 1000 in 2001, an increase of 0.091 per year (95% CI 0.081-0.101). After 2001 incidence rates remained constant (increase per year −0.010, 95% CI −0.045-0.024). Maternal age and ethnicity are known to influence the risk of HM. Highest incidences were observed in women under 20 and over 40 years of age. The proportion of deliveries accounted for by women over 40 years of age increased from 1.5% to 2.9%, whereas women under 20 accounted for 1.5% of deliveries. The proportion of live births of Asian descent increased from 2.6% to 3.7%.

Conclusion

The incidence of GTD in The Netherlands increased significantly from 1995 to 2008. This can partially be explained by increased maternal age and increased proportion of live births of Asian descent. Part of the increase might result from improved diagnostic techniques. However, these factors do not seem to account for the total observed increase and part of the increase therefore remains unexplained.     

Multiple metastatic gestational trophoblastic disease after a twin pregnancy with complete hydatidiform mole and coexisting fetus,following assisted reproductive technology: Case report and literature review

Objective

Twin pregnancy with complete hydatidiform mole and coexisting fetus (CHMCF) is rare and associated with severe complications during pregnancy and subsequent gestational trophoblastic disease (GTD). We encountered a case of multiple metastatic GTD after a twin pregnancy with CHMCF, following conventional in vitro fertilization (IVF). Only one case of metastatic GTD after CHMCF due to assisted reproductive technology (ART) has been reported. Here, we present the clinical course and reveal the clinical features of CHMCF after ART through a literature review.

妊娠滋养细胞疾病中EMT相关蛋白CK19和N-cad表达的研究

目的:探讨上皮细胞向间质转化(EMT)相关蛋白细胞角蛋白19(CK19)和神经钙黏蛋白(N-cad)在妊娠滋养细胞疾病发生、发展中的作用。方法:采用免疫组化SP法检测了41例正常早孕绒毛(NP)、31例葡萄胎(HM)、32例妊娠滋养细胞肿瘤(GTN)[26例侵蚀性葡萄胎(IM)+6例绒癌(CCA)]中CK19和N-cad的定位及表达情况。结果:NP组中CK19和N-cad蛋白相对表达均显著高于HM、GTN组(P0.05),HM组显著高于GTN组(P0.05)。CK19与N-cad的表达无相关性(r=0.202,P=0.268)。结论:伴随着滋养细胞恶性程度的升高,CK19和N-cad表达逐渐降低,提示EMT可能与滋养细胞的恶性转化有关。     

Twin pregnancy with a complete hydatidiform mole and co-existent live fetus: two case reports and review of the literature

Introduction  The aim of this study was to report the clinical features, management, and outcome of two cases of complete hydatidiform mole with a coexisting viable fetus and to review the literature. Case reports  In this article, we report on the well-documented follow-up of two cases of twin pregnancies with complete hydatidiform mole and a normal fetus. Genetic amniocentesis showed normal fetal karyotype in both of two cases. In the first case, a live male infant was delivered by a cesarean section because of severe maternal bleeding at 29 weeks of gestation. In the second case, termination of pregnancy was performed due to early onset of severe preeclampsia and vaginal hemorrhage. Conclusion  The chances of a live birth have been estimated between 30 and 35% and the risk of persistent trophoblastic disease is similar to singleton molar pregnancies in complete mole with coexisting fetus pregnancy. Therefore, in these pregnancies, expectant management instead of termination of pregnancy can be suggested.