MUC1在胚泡植入中的作用

MUC1是一种多态性的大分子糖蛋白，可在人子宫内膜上皮细胞表达。MUC1 mRNA及蛋白水平受激素和胚泡信号调节，并可被蛋白水解酶裂解，而佛波醇酯可刺激酶解过程，人工合成金属蛋白酶抑制因子、内源性组织金属蛋白酶抑制因子、肿瘤坏死因子-α蛋白酶抑制因子可以明显抑制该过程。MUC1可能是人类子宫内膜表达的调节囊胚植入的分子之一，对MUC1表达及调控机制的深入研究将有助于更好的了解胚泡植入过程，指导辅助生殖工作，提高辅助生殖技术的成功率。     

基质金属蛋白酶与胚泡植入

植入又称着床是指胚泡通过与子宫内膜的相互作用而埋入于宫内膜的过程。胚泡植入是建立妊娠的第一步，成功与否直接影响妊娠的结局。基质金属蛋白酶(MMPs)是一组锌依赖性的蛋白水解酶，降解细胞外基质(ECM)，与月经期内膜重塑、胚胎植入密切相关。     

基质金属蛋白酶与胚泡植入

植入又称着床是指胚泡通过与子宫内膜的相互作用而埋入于宫内膜的过程.胚泡植入是建立妊娠的第一步,成功与否直接影响妊娠的结局.基质金属蛋白酶(MMPs)是一组锌依赖性的蛋白水解酶,降解细胞外基质(ECM),与月经期内膜重塑、胚胎植入密切相关.     

基质金属蛋白酶与胚泡植入

植入又称着床是指胚泡通过与子宫内膜的相互作用而埋入于宫内膜的过程。胚泡植入是建立妊娠的第一步,成功与否直接影响妊娠的结局。基质金属蛋白酶(MMPs)是一组锌依赖性的蛋白水解酶,降解细胞外基质(ECM),与月经期内膜重塑、胚胎植入密切相关。     

胚泡着床及相关因素

胚泡着床的生理生化机制迄今尚不十分清楚，已知与激素，细胞因子，免疫因子，蛋白，肽和酶类物质等相关因素有关。这些物质调控着床微环境，直接影响胚泡活性和子宫内膜可接受性。     

MUC1在人正常月经周期子宫内膜中的表达

目的:探讨MUC1在人正常月经周期子宫内膜中的表达及其变化规律。方法:采用免疫组织化学法对35例人正常月经周期子宫内膜MUC l蛋白质进行组织学定位和定量测定,逆转录聚合酶链反应(RT-PCR)方法对此35例人正常月经周期子宫内膜MUC1 mRNA进行半定量分析。结果:MUC1蛋白质主要分布在宫腔上皮(LE)和腺上皮(GE)细胞顶端表面,增生期和分泌期均有表达,其中增生期MUC1仅有弱表达,分泌期表达增强,分泌中期达到高峰(P<0.05),分泌晚期其表达又下降。MUC1 mRNA表达分泌中期强于增生期(P<0.05)。结论:MUC1作为一种粘蛋白分子,在正常人子宫内膜中规律性表达,可能对内膜容受性的建立以及胚胎着床发挥着重要作用。     

白介素-1系统与胚泡着床

白介素 1系统在胚泡着床过程中起重要作用 ,本文阐述了白介素 1系统对下丘脑 垂体 卵巢轴神经内分泌功能的影响 ,及在女性生殖器中如卵巢、子宫内膜 ,以及胚泡及卵母细胞中的表达和白介素 1在生殖医学领域中的重要作用 ,为临床解决有关胚胎着床的疑难问题提供帮助     

白介素—l系统与胚泡着床

白介素—1系统在胚泡着床过程中起重要作用，本文阐述了白介素—1系统对下丘脑—全体—卵巢轴神经内分泌功能的影响，及在女性生殖器中如卵巢、子宫内膜，以及胚泡及卵母细胞中的表达和白介素—1在生殖医学领域中的重要作用，为临床解决有关胚胎着床的疑难问题提供帮助。     

粘蛋白MUC1与卵巢肿瘤研究进展

MUC1粘蛋白是一种分布于人上皮细胞表面高度糖化、高分子量的糖蛋白,在卵巢肿瘤细胞其表达水平上调,糖基化发生改变,从而影响肿瘤细胞的粘附力、免疫识别、转移,与卵巢肿瘤的发生、发展及预后相关.     

瘦素与胚泡着床

瘦素(leptin)是近年发现的肥胖基因(ob)编码的肽类激素，主要作用于中枢和外周，调节机体的能量代谢和脂肪贮存。近年研究表明leptin与妊娠和生殖调节有关。早孕蜕膜、绒毛都有leptin受体的表达，滋养层细胞还能合成并分泌leptin，提示leptin与胚泡着床有一定关系。leptin的合成和分泌受甾体激素调节。     

MUC1在侵润性胰腺导管乳头状黏液腺瘤表达的Meta分析

目的系统评价黏液素1(MUC1)对侵润性胰腺导管乳头状黏液腺瘤表达的意义。方法通过检索获得公开发表的研究免疫组化技术检测MUC1在胰腺导管乳头状黏液腺瘤表达的文献,筛选文献,评价文献质量并提取纳入文献中有关准确度的数据,将侵润性胰腺导管乳头状黏液腺瘤设为侵润组,非侵润性胰腺导管乳头状黏液腺瘤设为非侵润组,获得MUC1在此2组表达的四格表,以优势比(OR)为效应量指标。采用Review Manager4.2软件进行Meta分析,得到合并OR值及95%可信区间(95%CI),同时进行特异性及敏感性分析。结果最终进入系统评价的文献共有14篇研究,其中侵润性胰腺导管乳头状黏液腺瘤234例,非侵润性胰腺导管乳头状黏液腺瘤345例,Meta分析结果异质性检验,P=0.17,采用固定效应模式。合并OR值为4.88,95%CI为3.11～7.65。敏感性分析显示结论较为稳定。结论对目前相关研究结果的Meta分析显示,MUCl在IPMNs的表达可作为侵润性的指标,从而有助于手术方式的选择以及预后的评估。     

子宫内膜异位症在位内膜MUC1的表达变化及意义

目的:探讨子宫内膜异位症患者在位内膜黏蛋白-1(MUC1)的表达变化及意义。方法:采集子宫内膜异位症及输卵管因素不孕的54例患者的在位子宫内膜,采用免疫组织化学方法检测内膜MUC1的表达;分析内异症不同疾病分期与MUC1表达变化的相关性以及与对照组的差异性。结果:子宫内膜异位症患者在位内膜MUC1在不同月经周期的表达差异不明显,而与对照组比较表达明显减少;MUC1表达与内异症不同疾病分期存在相关性。结论:子宫内膜异位症患者在位内膜MUC1表达的减少与内异症疾病分期有密切相关性,可能是导致不孕的原因之一。     

MUC1在卵巢肿瘤组织的表达及其临床意义

目的 :监测 MUC1在卵巢肿瘤组织中的表达 ,探讨其对于卵巢肿瘤诊断及治疗的意义。方法 :采用免疫组织化学ABC方法 ,用 CA12 5抗体和从小鼠腹水中提取的 MUC1抗体对 2 0例卵巢癌、12例交界性卵巢瘤和 12例卵巢良性肿瘤组织进行检测。结果 :两种抗体的检测结果与病理诊断基本相符 ,良恶性表达存在显著性差异 ,阳性程度与临床分期及转移密切相关。结论 :MUC1在卵巢癌快速诊断及治疗监测中有重要意义。     

The effects of fertilization mode,embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes

Abstract

The aim of this study was to evaluate the influence of in vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI), fertilization mode embryonic morphology at day 3, and female age on blastocyst development, on the clinical outcomes of pregnancy after blastocyst transfer. A total of 471 cycles were retrospectively investigated. The rates of blastocyst formation and of good blastocyst morphology were higher in IVF than in ICSI cycles but there were no significant differences in the clinical pregnancies or in the miscarriage rates. The rates of formation of blastocyst and of blastocysts with good morphology were significantly higher from good-morphology embryos than from poor-morphology embryos. Nevertheless, 16.9% of the poor-morphology embryos reached the blastocyst stage. The total rates of blastocyst formation, and rates of clinical pregnancy and implantation were statistically similar in the age <35, 35–39, and >39 year groups, although tending to decrease with increasing age. When equal numbers of embryos were transferred on day 3, the rates of clinical pregnancy and implantation after blastocyst transfer were significantly higher in the <35 year age group than in the 35–39 and >39 year age groups, which were not significantly different. The miscarriage rates after embryo or blastocyst transfers were not statistically different in groups of similar age. Therefore, extended embryo culture up to the blastocyst stage could be implemented for women aged younger than 35 years to increase the pregnancy rate. For older women, transfer and vitrification of available embryos at day 3 and extended culture of morphologically poor embryos to the blastocyst stage for cryopreservation may improve the clinical outcome.     

卵巢上皮性肿瘤黏蛋白抗原4、5AC的表达相关性研究

目的探讨黏蛋白抗原(mucin antigen,MUC)4、5AC在卵巢上皮性肿瘤中的表达情况及其临床意义。方法采用免疫组织化学法对30例正常卵巢组织、30例卵巢良性上皮性肿瘤、30例卵巢交界性上皮性肿瘤和46例卵巢恶性上皮性肿瘤组织中MUC4、5AC的表达情况进行检测。结果 MUC4和MUC5AC在卵巢上皮性肿瘤中有不同程度的表达,MUC4在4组的阳性表达率分别为0、10%、40%、82.5%,MUC5AC在4组的阳性表达率分别为0、50%、40%、15%。结论 MUC4蛋白表达上调或MUC5AC蛋白表达下调可能参与了卵巢上皮性肿瘤的发生、发展过程,与肿瘤的浸润转移有关。     

Antitumor efficacy of MUC1-derived variable epitope library treatments in a mouse model of breast cancer

The identification of novel targets for cancer immunotherapy and the development of new vaccine immunogens are subjects of permanent interest. MUC1 is an overexpressed antigen found in most tumors, and its overexpression correlates with poor prognosis. Many attempts to direct the immune response against MUC1 in tumor cells have failed, including several clinical trials. We have previously developed an innovative Variable Epitope Library (VEL) vaccine platform that carries massively substituted mutant variants of defined epitopes or epitope regions as an alternative to using wild-type peptide sequences-based immunogens. Here, two murine MUC1-derived epitopes equivalent to the previously tested in cancer immunotherapy human MUC1 regions were used to generate VELs. We observed that vaccination with the 23L VEL immunogens, encompassing the entire signal peptide region of MUC1, reduces the tumor area compared to the wild-type sequence treatment. Contrastingly, vaccination with the MUC1 signal peptide-derived predicted CD8⁺+ T cell epitope-based VEL, 9MUC1spL, showed similar tumor area reduction as the wild-type treatment; however, a decrease in lung metastasis after 9MUC1spL treatment was observed. In addition, vaccination induced a large pool of CD8⁺ T cells which recognized most variant epitopes from 9MUC1spL. Also, we generated MUC1 variable number tandem repeat (VNTR)-based VELs that reduced the metastatic burden when dendritic cells and M13 recombinant bacteriophages were used as vaccine carriers. Collectively, our data demonstrate the immunogenic and antitumor properties of MUC1 signal peptide- and VNTR-derived VEL immunogens.     

MUC1基因疫苗对乳腺肿瘤抑制的实验研究

目的:研究人粘蛋白MUC1基因DNA疫苗诱导小鼠体内免疫应答及对乳腺肿瘤的特异性抑制作用。方法:采用股四头肌注射法接种PcDNA3.1(+)-MUC1质粒,通过ELISA法检测小鼠血清MUC1抗体、脾细胞产生IL-2和IFN-γ的量及血清中TNF水平,通过乳酸脱氢酶释放法测定CTL对MCF-7细胞的杀伤活性。结果:经PcDNA3.1(+)-MUC1免疫小鼠后脾细胞分泌IL-2、IFN-γ及血清TNF水平较对照组明显增高,差异有统计学意义;在效靶比为100∶1、50∶1、25∶1、12.5∶1时,MUC1基因疫苗免疫组小鼠CTL对人乳腺癌细胞系MCF-7杀伤率分别为63.8%、51.2%、43.5%、22.5%,较空载体PcDNA3.1(+)组小鼠和灭菌生理盐水组小鼠均明显升高,差异有统计学意义(P<0.05)。结论:MUC1基因DNA疫苗能够激活小鼠Th1细胞,诱导小鼠产生抗MUCl特异性抗体,诱导产生杀伤高表达MUC1基因的乳腺癌细胞的CTL,为MUC1基因疫苗用于乳腺肿瘤生物治疗提供了一定的实验依据。     

MUC1体外转染脐带血DC疫苗抗乳腺肿瘤的免疫效应研究

目的:研究人粘蛋白核心肽-连续重复序列(MUC1-VNTR)基因转染的脐血DC疫苗抗乳腺肿瘤的免疫效应。方法:提取人脐带血淋巴细胞,培养脐血树突状细胞(DCs),采用Lipofectamine2000阳离子脂质体法将MUC1-VNTR转染入脐血DC,用Western印迹法检测MUC1-VNTR基因的表达;与自体T细胞共培养,用MTT法检测转染MUC1基因的脐血DC所致敏的细胞毒性淋巴细胞对乳腺癌MCF-7的杀伤活性;ELISA法检测其刺激T细胞分泌IFN-γ的能力。结果:Western印迹法检测到1条MUC1-VNTR基因表达的特殊条带,转染MUC1-VNTR基因的脐血DC对MUC1表达阳性的乳腺癌细胞系MCF-7的杀伤活性显著高于单纯脐血DC组(P<0.05),而且其刺激同种T细胞分泌高水平的IFN-γ,显著高于未转染的脐血DC(P<0.05)。结论:MUC1-VNTR基因转染的人脐血树突状细胞可诱导特异性CTL,产生有效的针对MUC1阳性乳腺癌细胞MCF-7的杀伤效应,并诱导特异性抗乳腺癌免疫应答。     

MUC1 and survivin combination tumor gene vaccine generates specific immune responses and anti-tumor effects in a murine melanoma model

MUC1 and survivin are ideal tumor antigens. Although many cancer vaccines targeting survivin or MUC1 have entered clinical trials, no vaccine combining MUC1 and survivin have been reported. Due to tumor heterogeneity, vaccines containing a combination of antigens may have improved efficacy and coverage of a broader spectrum of cancer targets. Here, cellular responses and anti-tumor activities induced by a combination of DNA vaccine targeting MUC1 and survivin (MS) were evaluated. Results showed that CTL activity and inhibition of tumor growth were obviously enhanced in mice immunized with the combined vaccine in a protection assay. However, in order to enhance the therapeutic effect in the treatment assay, a recombinant adenovirus (rAd) vaccine expressing MUC1 and survivin (Ad-MS) was used as a booster following the DNA vaccine prime. Meanwhile, IL-2 promoting T cell proliferation was used as an immunoadjuvant for the DNA vaccine. Results showed that the CTL activity response to the DNA vaccine was enhanced nearly 200% when boosted by the rAd vaccine and was further enhanced by nearly 60% when combined with the IL-2 adjuvant. Therefore, DNA prime combined with rAd boost and IL-2 (MS/IL2/Ad-MS) adjuvant was considered as the best strategy and further evaluated. Multiple cytokines promoting cellular immune responses were shown to be greatly enhanced in mice immunized with MS/IL2/Ad-MS. Moreover, in the treatment assay, the tumor inhibition rate of MS/IL2/Ad-MS reached up to 50.1%, which may be attributed to the enhancement of immune responses and reduction of immunosuppressive factors in tumor-bearing mice. These results suggested that immunization with the combination vaccine targeting MUC1 and survivin using a DNA prime–rAd boost strategy along with IL-2 adjuvant may be an effective method for breaking through immune tolerance to tumors expressing these antigens with potential therapeutic benefits in melanoma cancer.