Clinicopathological and Ultrasonic Features of Triple-Negative Breast Cancers: A Comparison with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Breast Cancers

The purpose of this study was to analyze the clinicopathological and ultrasound characteristics of triple-negative breast cancers (TNBCs) and compare these findings with those for hormone receptor-positive (HR-positive)/human epidermal growth factor receptor-2-negative (HER-2-negative) tumors. Seventy-five TNBCs and 135 HR-positive/HER-2-negative breast cancers were reviewed. Data from conventional ultrasound, Doppler vascularity and elastography were included in the analysis. TNBCs had a higher histologic grade and Ki-67 level. On ultrasound, TNBCs often appeared as microlobulated, markedly hypo-echoic masses with an abrupt interface boundary, posterior acoustic enhancement, absence of calcifications and more characteristics of surrounding tissue. Results from multivariate regression analysis revealed that margin, posterior acoustic features and surrounding tissue features of tumors were independent predictive factors in differentiating TNBCs from HR-positive/HER-2-negative tumors. Our results suggest that a thorough evaluation of sonographic findings might be useful in discriminating between TNBCs and HR-positive/HER-2-negative tumors, which may provide accurate evidence for clinical early diagnosis.     

女性激素在胆囊胆固醇结石形成中的作用的研究现状

目的综述女性激素致胆囊胆固醇结石形成的机制,为预防雌、孕激素致石形成寻找途径。方法复习有关雌、孕激素致石形成的文献,总结其致石机制。结果雌激素主要通过核效应机制影响胆固醇代谢导致胆固醇结石形成,也可通过非核效应促使胆固醇成核及影响胆汁排空参与结石形成。孕激素通过核效应机制影响介导胆囊平滑肌收缩舒张的G蛋白α亚基损伤胆囊运动,通过非核效应途径影响离子通道及信号传导削弱胆囊运动,但孕酮的非核效应在结石形成中可能不起重要作用。结论女性激素致石机制复杂,明确其相关致石机制可为预防雌、孕激素致石形成开辟新途径。     

Peptidoglycan inhibits progesterone and androstenedione production in bovine ovarian theca cells

Uterine bacterial infection perturbs uterine and ovarian functions in postpartum dairy cows. Peptidoglycan (PGN) produced by gram-positive bacteria has been shown to disrupt the ovarian function in ewes. The aim of this study was to determine the effect of PGN on steroid production in bovine theca cells at different stages of follicular development. Bovine theca cells isolated from pre- and post-selection ovarian follicles (<8.5 mm and >8.5 mm in diameter, respectively) were cultured in vitro and challenged with PGN. Steroid production was evaluated by measuring progesterone (P4) and androstenedione (A4) concentration in culture media after 48 h or 96 h of culture. Bovine theca cells expressed PGN receptors including Toll-like receptor 2 and nucleotide-binding oligomerization domain 1 and 2. Treatment with PGN (1, 10, or 50 μg/ml) led to a decrease in P4 and A4 production by theca cells in both pre- and post-selection follicles. The mRNA expression of steroidogenic enzymes were decreased by PGN treatment. Moreover, A4 production was further suppressed when theca cells of post-selection follicles were simultaneously treated by PGN and lipopolysaccharide (0.1, 1, or 10 μg/ml). These findings indicate that bacterial toxins may act locally on ovarian steroidogenic cells and compromise follicular development in postpartum dairy cows.     

Progesterone receptors A and B and estrogen receptor alpha expression in normal breast tissue and fibroadenomas

Fibroadenomas are the most common benign breast tumors, occurring mainly in young women. Their responses to the hormonal environment are similar to those of normal breast tissue, which suggests that steroid receptors may play a role in tumor development. We evaluated the gene and protein expression of progesterone receptors A and B (PRA and PRB) and the protein expression of estrogen receptor α (ER-α) in fibroadenoma samples, comparing with adjacent normal breast tissue, from 11 premenopausal women. Progesterone and estradiol levels were determined. No alterations in the PRs gene and protein expression and the ER-α protein expression were observed between the follicular and luteal phases, in normal breast versus fibroadenomas. Protein levels of PRA and PRB were higher in fibroadenomas compared to normal breast tissue (P = 0.038 and P = 0.031), while the PRs mRNA levels were similar in both tissues (P = 0.721 and P = 0.139). There were no differences in ER-α protein expression between normal breast tissue and fibroadenomas (P = 0.508). The PRA:PRB ratio was similar in the tissues, and also showed a strong correlation in both (r = 0.964, P = 0.0001). Our data suggest a role of PRs in the growth and development of fibroadenomas, although without alterations of the PRA:PRB ratio in these tumors. The absence of alterations in ER-α protein levels could be a characteristic behavior of fibroadenomas, unlike breast cancer.     

类固醇激素在乳腺癌中的作用及对肿瘤干细胞的影响

类固醇激素尤其雌激素和孕激素在乳腺癌的发病、进展和治疗中起着重要作用。与此同时,大量的研究证实肿瘤干细胞在乳腺癌发生、进展和转移过程中也起着关键作用。在乳腺癌临床治疗中,尽管肿瘤细胞经过常规抗内分泌治疗后受到了明显的抑制,但仅需少量的乳腺肿瘤干细胞(Breast cancer stem cells,BCSCs)存在,仍可维持肿瘤的再生长。以往大量的研究多集中在激素对正常乳腺发育及其与乳腺癌的相关性方面,最近,更多的研究观察激素对乳腺肿瘤干细胞活性影响,这为乳腺癌治疗和肿瘤干细胞研究开辟了新的方向。本文全面讨论类固醇激素(雌激素和孕激素)在乳腺癌中的作用及其对乳腺肿瘤干细胞的活性调节。     

孕激素诱导的microRNA-152对子宫内膜上皮细胞增殖的抑制作用

目的 研究孕激素诱导microRNA-152的表达及其对子宫内膜上皮细胞增殖的抑制作用。方法 培养子宫内膜上皮细胞Ishikawa,将其分为4组,分别为空白对照组（control,C组）、10-8mol/L雌激素处理组（estrogen,E组）、10-6mol/L孕激素处理组（progesterone,P组）以及相应浓度的雌、孕激素联合处理组（estrogen plus progesterone,E&P组）,利用实时定量PCR检测microRNA-152的成熟体microRNA-152-3p的表达。将microRNA-152-3p拟似剂转染雌激素预处理的细胞,microRNA-152-3p抑制剂转染雌、孕激素联合处理的细胞,CCK-8法观察microRNA-152-3p对细胞增殖的影响。利用microRNA靶蛋白数据库预测microRNA-152-3p的靶蛋白,并利用Western blot加以验证。结果 实时定量PCR结果显示E组与C组相比,其细胞microRNA-152-3p的表达量无明显变化（ P＞0.05）;P 组细胞microRNA-152-3p的表达量相比C组增加（ P<0.05）;且E&P组的microRNA-152-3p表达量高于C组和P组（ P均<0.05）。对microRNA-152-3p靶蛋白的预测表明CDC14A是其一个重要的靶蛋白。转染microRNA-152-3p拟似剂能够抑制雌激素对子宫内膜上皮细胞的增殖效应（ P<0.05）,同时下调CDC14A蛋白的表达（ P<0.05)。而microRNA-152-3p抑制剂能一定程度解除孕激素对子宫内膜上皮细胞的增殖抑制效应（ P<0.05）,同时上调CDC14A蛋白水平（ P<0.05)。结论 孕激素可通过诱导microRNA-152-3p的表达抑制子宫内膜上皮细胞的增殖,CDC14A蛋白可能是microRNA-152-3p抑制子宫内膜上皮细胞增殖的靶蛋白。     

Pessaire et prévention de l’accouchement prématuré

Cervical pessary is a promising tool to prevent preterm birth in high risk pregnant women with shortened midtrimester ultrasonographic cervical length. It is well tolerated by women. PECEP and ProTWIN trials have opened new fields of clinical research. Their results suggest that cervical pessary may prevent preterm birth in women with (i) singleton and cervical length ≤ 25 mm at 18–22 weeks, and with (ii) twins and cervical length ≤ 37 mm at 16–22 weeks. These results must be confirmed by other randomized controlled trial before a generalization of cervical pessary in these situations. The role of cervical pessary in the existing strategies to prevent birth (progesterone, cerclage or combinations thereof) has to be determined.     

Quality of embryos transferred and progesterone levels are the most important predictors of live birth after fresh embryo transfer: a retrospective cohort study

Purpose

To identify the independent predictors of live birth following IVF, and to assess the role of cohort-specific parameters, including antral follicle count (AFC), the number of oocytes retrieved, the total number of embryos, and the total number of good-quality embryos, in fresh IVF cycles.

Methods

A retrospective cohort study of 2,525 infertile women undergoing IVF between 2002 and 2007. The hypothesis that the number and quality of embryos transferred capture the effects previously attributed to cohort-specific variables was examined using mediation analysis and spline analysis. Independent predictors were identified by a bootstrap algorithm. Multivariable logistic regression was performed and the proportion of explained variation was measured to compare the relative importance of transfer-specific vs. cohort-specific predictors.

Results

The number of good-quality embryos transferred and progesterone level on the day of hCG administration ranked as the two most important predictors of live birth. Prospects of pregnancy started to decrease after progesterone level exceeded 0.6 ng/ml. The achievement of live birth in a fresh IVF cycle is primarily determined by the number and quality of embryos transferred, rather than by embryo cohort-specific variables.

Conclusions

The associations between cohort-specific variables and live birth in a fresh IVF cycle are completely mediated by the quality of embryos transferred. Progesterone level on the day of hCG administration is an independent predictor of pregnancy and merits further investigation.     

Regulation and disruption of hamster sperm hyperactivation by progesterone, 17β-estradiol and diethylstilbestrol

Purpose

Hyperactivation of hamster sperm is dose-dependently enhanced by progesterone (P) and 17β-estradiol (E). In the first part of the present study, enhancement of hyperactivation in response to the concentrations of P and E was examined in detail and in the second part, it was examined whether enhancement of hyperactivation by P and E was disrupted by diethylstilbestrol (DES).

Methods

Hamster spermatozoa were hyperactivated by incubation in modified Tyrode’s albumin lactate pyruvate medium with P, E and/or DES. After spermatozoa were recorded using a video-microscope, observations were quantified by manually counting the numbers of total, motile and hyperactivated spermatozoa.

Results

Hyperactivation was enhanced in response to the concentrations of P and E. When spermatozoa were exposed to DES with E, moreover, DES significantly and strongly suppressed P-enhanced hyperactivation by accelerating the effect of E, but DES itself only weakly suppressed P-enhanced hyperactivation.

Conclusions

Enhancement of hyperactivation was regulated by the concentrations of P and E, suggesting that in vivo hamster spermatozoa are hyperactivated through “monitoring” these concentrations in the oviduct. DES in combination with E suppressed P-enhanced hyperactivation, suggesting that DES significantly disrupts hyperactivation by acting as an accelerator of the effect of E.