子宫内膜异位症和腺肌症患者子宫内膜雌激素受体的时空表达

目的　研究子宫内膜异位症和子宫腺肌症子宫内膜各种细胞中雌激素α和 β受体的表达模式 ,为探索子宫内膜异位症和子宫腺肌症的致病机理提供依据。　方法　 10 8例患有内膜异位症、腺肌症、两症并发组和对照组子宫内膜组织 ,常规光镜下按Noyes分期标准行形态学分期。采用免疫组织化学的方法观察不同月经周期时相子宫内膜腺上皮、基质和血管内皮细胞中雌激素受体ERα和ERβ的表达。　 结果　与对照组相比 ,ERα信号强度在各组相应的细胞类型、相应的时相无显著差异 ,但子宫内膜腺上皮细胞、基质细胞和血管内皮细胞中显示阳性信号的细胞比例增大 ,且腺上皮细胞质普遍出现ERα阳性信号。子宫内膜异位症和腺肌症的血管内皮细胞中ERα阳性细胞数显著增加。ERβ在各组的表达模式与对照组相比无明显差异 ,甚至略呈下降趋势。　结论　人子宫内膜中ERα为雌激素效应的主要受体亚型 ,表达ERα的腺上皮、基质和血管内皮细胞数量的增多以及腺上皮细胞质普遍出现ERα阳性信号可能与这两种疾病的发病密切相关 ;ERβ并不参与这一过程。     

产后小鼠子宫内膜边缘群干/祖细胞的分离纯化

目的分离和纯化小鼠子宫内膜边缘群(side population,SP)干/祖细胞,为进一步探讨产后子宫修复的细胞机制奠定基础。方法分别采用酶消化和机械分离结合法与机械研磨分离的方法,原代分离小鼠子宫内膜上皮细胞与基质细胞,通过Hoechst33342-SP法(对照加入维拉帕米),使用流式细胞仪检测子宫内膜SP细胞。结果未孕小鼠子宫内膜上皮与基质中均无明确SP干/祖细胞,产后哺乳期后的小鼠子宫内膜基质中含有SP干/祖细胞达(3.44±1.59)%。结论本研究初步检测到小鼠产后子宫内膜中含有SP干/祖细胞。产后更多SP细胞的出现可能与修复损伤的子宫内膜有关。这群SP细胞是子宫原位干细胞还是有其他来源,如何参与子宫内膜的修复,其分子机制如何,尚待进一步研究。     

人子宫内膜基质细胞及上皮细胞的分离

为获得供人胚胎联合培养的人子宫内膜上皮和基质细胞标本，必须进行人子宫内膜上皮和基质细胞的分离和培养。为此，我们对传统的Ｋｅｖｉｎ［１］方法进行改进，现介绍如下。一、材料及方法１．标本来源：选自１９９６年１０月～１９９７年１２月在山东省立医院妇产科因子宫肌瘤做子宫切除术病例１０例，年龄３６～４８岁，月经周期规律（２８～３２天），术前３个月未用激素，病理检查为增殖期至早分泌期子宫内膜。２．子宫内膜上皮细胞及基质细胞的分离：参照Ｋｅｖｉｎ等［１］方法加以改良：术后立即刮取子宫内膜，置于含无菌Ｄ－Ｈａｎ…     

无排卵性功能失调性子宫出血患者子宫内膜雌、孕激素受体及基质金属蛋白酶表达变化的研究

目的研究无排卵性功能失调性子宫出血(功血)患者子宫内膜雌激素受体(ER)、孕激素受体(PR)、IV型胶原、基质金属蛋白酶-9(MMP-9)及其抑制物-1(TIMP-1)的表达,探讨无排卵性功血的发病机制。方法采用免疫组化法检测20例正常增殖期子宫内膜(对照组)和66例无排卵性功血患者(病例组)子宫内膜腺上皮和基质细胞ER、PR、IV型胶原、MMP-9及TIMP-1表达。结果病例组子宫内膜腺上皮和基质ER、PR表达高于对照组(P<0.05),MMP-9水平明显增加(P<0.05),MMP-9/TIMP-1比值升高(P<0.01),IV型胶原含量明显下降(P<0.01)。相关分析显示,无排卵性功血患者子宫内膜MMP-9水平与ER、PR均呈正相关(r=0.605,P<0.05;r=0.697,P<0.05)。结论无排卵性功血患者子宫内膜出血原因可能与雌激素作用下ER、PR表达失调有关,且MMP-9水平异常升高,导致细胞外基质过度降解,临床表现为子宫不规则出血。     

子宫内膜容受性治疗方法的新进展

胚胎质量与子宫内膜容受性是决定胚胎能否成功种植的关键。子宫内膜容受性障碍是导致胚胎种植失败的主要原因。近年来,如何改善子宫内膜容受性、提高体外受精-胚胎移植(IVF-ET)技术的胚胎种植率及临床妊娠率已经成为研究的热点。本文通过回顾文献,从增加子宫动脉血流、机械损伤子宫内膜、宫腔灌注某些与子宫内膜容受性相关的细胞因子、药物抑制子宫收缩等方面,对近年来一些研究的进展和新方法的探索进行了阐述。虽然其中的某些治疗方法可以有效提高IVF-ET技术的临床妊娠率,但是仍需高质量的大样本随机双盲对照研究证明其有效性,也亟待制定规范治疗方案及适应证。     

HOXA10在子宫内膜组织周期性表达与调控机制

HOXA10基因是多基因家族的转录调节基因之一,参与生殖道发育、胚胎植入的调控、细胞定向分化和增殖.近年来研究发现,HOXA10通过激活或抑制下游靶基因的转录来诱导子宫内膜成熟,并指导胚胎着床,在决定子宫内膜容受性方面起重要作用,且在子宫内膜异位症(EM)及其相关不育发病中发挥作用,EM患者子宫内膜容受性(endometrial receptivity)发生改变可能是其发生不育的原因之一.     

在植入和妊娠早期子宫内膜细胞特异基因激活

在植入和妊娠早期子宫内膜细胞特异基因激活ＬｉｎｄａＴｓｅｎｇ引言雌激素和孕激素调节人子宫内膜的生长和分化。在月经周期１０～１４天，子宫内膜每一成分，上皮性腺体、间质细胞和子宫内膜微血管系统迅速生长并达高峰。在月经周期中，腺上皮细胞形态显著改变。相反，...     

HOXA11在人子宫内膜和早孕蜕膜中的表达及与不育的关系

目的检测HOXA11蛋白在正常月经周期子宫内膜、早孕蜕膜和不明原因不育子宫内膜组织中的表达,探讨HOXA11与不明原因不育及雌孕激素受体(ER、PR)表达的相关性。方法采用免疫组织化学和Western-Blot方法对38例正常子宫内膜、15例早孕蜕膜和19例不明原因不育子宫内膜组织中HOXA11、ER及PR的表达。结果HOXA11蛋白在子宫内膜腺上皮和基质细胞均有表达,以分泌中晚期子宫内膜和早孕蜕膜表达量较高;在不育内膜的表达量显著降低(P<0.05);ER、PR在各组表达量的变化与HOXA11相同,即分泌中晚期子宫内膜和早孕蜕膜的表达量较高,而在不育内膜的表达量显著下降(P<0.05)。结论HOXA11基因在着床期子宫内膜的分化、发育以及着床后妊娠的维持起一定作用;HOXA11表达量下降与ER、PR表达量降低相关;HOXA11表达下降或缺失可能是女性不明原因不育的原因之一。     

胚泡围着床期子宫内膜细胞的增殖、分化与凋亡

围着床期子宫内膜细胞的增殖、分化与凋亡以一种时空有序和细胞特异性的方式发生是胚泡着床成功的重要条件。子宫内膜细胞的增殖、分化与凋亡是受雌、孕激素宏观调控 ,并受局部粘附分子 细胞因子 生长因子以及胚泡严格调控。了解围着床期子宫内膜细胞的增殖、分化与凋亡以及相关调节因素 ,对于我们深入理解胚泡着床机制具有重要意义。     

正常与异常子宫内膜中Bc1-2、Bax mRNA表达

为了解正常和异常子宫内膜中 Bc1 -2和 Bax m RNA的表达及与凋亡的关系。应用原位杂交方法检测了 2 7例正常子宫内膜 ,1 2例子宫内膜增殖症和 1 0例癌变子宫内膜 Bc1 -2和 Bax m RNA的表达情况。结果 :正常子宫内膜组织腺细胞 Bc1 -2与 Bax m R-NA表达的比例与子宫内膜的周期性变化密切相关 ,Bc1 -2 m RNA表达在增殖期增强 ,分泌期减弱 ,Bax m RNA表达则相反。增殖症和癌变子宫内膜组织中 ,Bc1 -2和 Bax m RNA表达呈正相关 (rs=0 .886 ,P<0 .0 5) ,随着子宫内膜由良性增生到恶性增生 ,Bc1 -2 m R-NA表达逐渐减弱至丧失表达 ;Bax m RNA在增殖症子宫内膜中 ,随着增生的异型化 ,表达逐渐增强 ,而在癌变子宫内膜中 ,随着病理分级的降低 ,表达逐渐降低。结论 :Bc1 -2和Bax基因对于维持正常子宫内膜周期性变化的平衡起着重要作用 ,在增殖症和癌变子宫内膜中表达的异常变化可能与子宫内膜癌生物学行为和预后相关。     

Stromal Mediation of Radiation Carcinogenesis

Ionizing radiation is a well-established carcinogen in human breast and rodent mammary gland. This review addresses evidence that radiation elicits the critical stromal context for cancer, affecting not only frequency but the type of cancer. Recent data from the breast tumors of women treated with radiation therapy and the cellular mechanisms evident in experimental models suggest that radiation effects on stromal-epithelial interactions and tissue composition are a major determinant of cancer development.     

Regulation of lnvasive Potential of Human Prostate Cancer Cell Lines by Hepatocyte Growth Factor

Background: The growth and progression of prostate cancer depends on the stromal-epithelial interaction which is under paracrine control. Hepatocyte growth factor (HGF), produced by mesenchymal cells, is a multifunctional growth factor stimulating the movement and growth of epithelial cells including cancer cells. We therefore assessed the relationship between the invasive potential of prostate cancer and HGF in vitro.
Methods: Three human prostate cancer cell lines were used including PC-3 and DU145 (androgenindependent), and LNCaP (androgen-dependent). We studied the expression of the HCF receptor c-met proto-oncogene (c-met) by Western blotanalysis, and alsodetermined theeffectsof HGF on cell scattering, and the mechanisms of invasion and proliferation, by microscopic observation, the matrigel invasion chamber assay, and the MTT assay.
Results: c-met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was increased cell motility in the scatter assay and an increased cell invasive potential in the matrigel invasion chamber assay by stimulation with HGF only with DU145 cells.
Conclusion: HGF plays an important role in the invasion and metastasis of the DU145 cell line through a paracrine mechanism mediated by the c-metreceptor. In the PC-3 cell line, the lack of downstream signal transduction after the c-met receptor is suggested.     

血管疾病的表观遗传学研究进展

表观遗传学指独立于DNA核苷酸序列本身的基因表达的可遗传改变,其主要机制包括DNA甲基化、组蛋白修饰和非编码RNA等,这些机制共同作用调控基因的特异性表达。血管疾病是由环境因素和遗传因素相互作用引发的一种慢性疾病。近年来,越来越多的研究证实表观遗传调节在血管疾病的发生发展中具有重要的作用。本文对表观遗传学在血管疾病中的最新研究进展进行综述。     

Unraveling complexity of antibody-mediated rejections,the mandatory way towards an accurate diagnosis and a personalized treatment

Antibody-mediated rejection (ABMR) remains one of the most challenging issues after organ transplantation and particularly after kidney transplantation. Despite many progresses during the last decade, ABMR is still the main cause of kidney graft loss and this all over the post- transplant period.In this review, we describe the recent knowledge about molecular and cellular mechanisms involved in ABMR. We focused our report on the role of the complement pathway in the process of ABMR and we give some insights into the role of inflammatory cells, NK lymphocytes and the role of endothelial cells. We further describe the potential role of non-HLA antibodies, of which the importance has been increasingly emphasized in recent years.Overall, this report could be of interest for all physicians who are working in the field of organ transplantation or who are working in the field of immunology. It gives essential information to understand new diagnosis advances and further therapeutic approaches.Antibody-mediated rejection (ABMR) is the leading cause of graft failure ([1,2]). In contrast to T-cell mediated rejection usually sensitive to steroids, active ABMR remains a therapeutic challenge. ABMR diagnosis relies on the presence of renal injuries and donor-specific antibodies (DSA) (HLA and non HLA antibodies) with sometimes the evidence of interaction between DSA and graft endothelium. Regularly revised during expert conferences, ABMR definition is currently categorized as active or chronic active. [3] The emergence of validated molecular assays targeting a better phenotyping of ABMR and the recent advances regarding the detrimental effect of DSA directed against minor antigens open the way to a better assessment of the heterogeneity of ABMR. In this review, we will address new aspects of ABMR regarding its mechanisms, diagnosis and treatments.     

Future opportunities for the diagnosis and treatment of prostate cancer

Despite recent advances, current diagnostic tests and treatment of prostate cancer have limitations. In the last few years, numerous biomolecules have been investigated with the aim of improving diagnosis, including kallikrein-like proteases, growth factors and neuroendocrine markers. Analysis of susceptibility genes has also been a focus of attention. Extensive research into new therapeutic approaches is also underway, including targeting angiogenesis, immune regulation and stromal-epithelial interactions. Gene therapy, gene chip technology and proteomics have emerged as promising innovations. The host of novel diagnostic markers and therapies require appropriate validation, both phenotypical and functional. A further consideration is the need to re-evaluate clinical trial design and end points to facilitate progression of promising targets through the clinical trial process. Overall, the outlook for the treatment of prostate cancer looks promising, with any advances likely to require both a multimodal and multidisciplinary approach.     

Transforming growth factor beta in the human prostate: its role in stromal-epithelial interactions in non-cancerous cell culture

BACKGROUND: Stromal-epithelial interactions play a critical role in prostate development, but the precise mechanisms are still unknown. Transforming growth factor-beta (TGFbeta) could be a potential mediator of these interactions, but there is as yet no clear demonstration of its role. METHODS: Separate cultures and co-cultures of fibroblasts and epithelial human prostate cells were performed. We measured TGFbeta1 and TGFbeta2 secretion by specific ELISA assay, cell growth by DNA assay, and TGFbeta type II receptor expression by RT-PCR. RESULTS: Co-culture resulted in a 20% inhibition of epithelial cell growth, similar to that obtained after TGFbeta treatment (2 ng/ml for 48 hr), but without affecting fibroblast proliferation. This was accompanied by a five- to six-fold increase in epithelial TGFbeta2 secretion. CONCLUSIONS: These results demonstrate for the first time that TGFbeta2 secretion by prostate epithelial cells is under the direct control of a diffusible factor secreted by fibroblasts. They emphasize the role of TGFbeta in stromal-epithelial interactions.     

Inflammatory processes in the acute respiratory distress syndrome

The clinical presentation of acute respiratory distress syndrome (ARDS) results from acute inflammation and tissue damage affecting the gas exchange apparatus of the lung. Basic science investigations into the cellular and molecular pathophysiology of ARDS and clinical studies emphasizing the crucial role of mechanical ventilation strategies in determining the outcome for patients have been the major recent advances in this field. By contrast relatively little is known about the mechanisms by which pulmonary inflammatory processes are switched off or how the lung repairs itself. Therapeutic advances have not yet followed the elucidation of the role of individual mediators of pulmonary inflammation. Hopefully improved supportive techniques, methods to predict patients who will develop ARDS and the recognition that large well designed multi-centre trials will be required will lead to the emergence of specific and effective pharmacotherapies.