Development of leiomyosarcoma of the uterus in MMTV-CR-1 transgenic mice

Overexpression of Cripto-1 (CR-1) in FVB/N mice using the MMTV-LTR promoter results in increased mammary tumourigenesis in these female transgenic mice (MMTV-CR-1). Here, we characterize uterine tumours that developed in 15/76 (19.7%) of MMTV-CR-1 female nulliparous or multiparous mice during 24 months of observation compared with 0/33 (0%) of FVB/N normal control mice observed during the same time period (p < 0.01). The uterine tumours collected from the MMTV-CR-1 mice were classified as leiomyosarcomas and found to express the CR-1 transgene by polymerase chain reaction analysis and immunohistochemistry. Detection by western blot analysis showed higher levels of phosphorylated (P) forms of c-src, Akt, GSK-3beta, and dephosphorylated (DP)-beta-catenin in lysates from MMTV-CR-1 uterine leiomyosarcomas in comparison with lysates from normal control FVB/N uteri. Immunostaining showed increased nuclear localization of beta-catenin in the MMTV-CR-1 uterine leiomyosarcomas. Increased immunostaining for CR-1 was detected in 9/13 (69.2%) cases of human leiomyosarcoma compared with staining in 3/15 (20%) human leiomyoma sections. Stronger immunostaining for P-src, P-Akt, P-GSK-3beta and increased nuclear localization of beta-catenin was also seen in human leiomyosarcomas in comparison with leiomyomas. Normal human uterine smooth muscle (UtSM) cells treated with exogenous soluble rhCR-1 showed increased levels of P-src, P-Akt, P-GSK-3beta and dephosphorylated (DP)-beta-catenin and increased proliferation (p < 0.05) and migration (p < 0.01) in comparison with untreated control UtSM cells. Inhibitors against c-src, Akt or beta-catenin, individually or in combination, significantly reduced CR-1-induced migration. These results suggest a role for CR-1 during uterine tumourigenesis either directly by activating c-src and Akt and/or via cross-talk with the canonical Wnt signalling pathway, as suggested by the increased expression of P-GSK-3beta, DP-beta-catenin, and increased nuclear localization of beta-catenin in human and MMTV-CR-1 mice leiomyosarcomas.     

Immune responses in the human female reproductive tract

Mucosal surfaces are key interfaces between the host and its environment, but also constitute ports of entry for numerous pathogens. The gut and lung mucosae act as points of nutrient and gas exchange, respectively, but the physiological purpose of the female reproductive tract (FRT) is to allow implantation and development of the fetus. Our understanding of immune responses in the FRT has traditionally lagged behind our grasp of the situation at other mucosal sites, but recently reproductive immunologists have begun to make rapid progress in this challenging area. Here, we review current knowledge of immune responses in the human FRT and their heterogeneity within and between compartments. In the commensal-rich vagina, the immune system must allow the growth of beneficial microbes, whereas the key challenge in the uterus is allowing the growth of the semi-allogeneic fetus. In both compartments, these objectives must be balanced with the need to eliminate pathogens. Our developing understanding of immune responses in the FRT will help us develop interventions to prevent the spread of sexually transmitted diseases and to improve outcomes of pregnancy for mothers and babies.     

Pulmonary benign metastasizing leiomyoma: a case report

Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity usually occurring in females with history of uterine leiomyoma, and it is preferential to metastasize to the lung and appears as a histopathologic benign tumor of smooth muscle origin. In this article, the clinical and pathological data from 1 patient with PBML were analyzed. Chest CT scan showed that multiple well-defined nodules in the both lobes of the lungs. The tumor cells in the lung were well differentiated, and the pattern of tumor was similar to the original tumor. IHC identified it originated from smooth muscle cells, consistent with the diagnosis of PBML. Positive staining of estrogen and progestogen receptors was detected in both the leiomyoma and the metastasizing lesions. During two years of observation, pulmonary function parameters were within normal limits and there was no evidence of tumor recurrence.     

Effect of Extract of Leaf and Seed of Piper guineense on Some Smooth Muscle Activity in Rat,Guinea-pig and Rabbit

Extracts of the leaf and seed of Piper guineense were separately prepared and their pharmacological effects screened using smooth muscle of the gastrointestinal tract and uterus. The leaf extract enhanced both the frequency and tone of spontaneous contractions of rabbit jejunum and induced contraction of guinea-pig ileum, which were blocked by atropine. The seed extract had the opposite effect on rabbit jejunum, an inhibition which was antagonized by prazocin, and little or no effect on guinea-pig ileum. Both extracts had a stimulant effect on rat uterine muscle, the seed extract to a lesser extent.     

宫腔微生物群与女性不孕症的研究进展

宫腔微生物群与多种妇科疾病密切相关,微生物群失衡与女性不孕症有关。通过探索不孕症患者宫腔微生物组成及变化后发现,特定菌种出现或菌群构成改变会影响妊娠结局。针对微生物进行相关治疗后,通过成功纠正宫腔微生物群失衡状态可以提高临床妊娠率。为此研究者正深入研究不孕症与宫腔微生物群的相关性,试图通过相关治疗改善子宫内膜容受性,尝试将宫腔微生物状态作为妊娠结局的预测因子。因此,本文就近年来对宫腔微生物群特征、宫腔微生物群与不孕症的关系及治疗的相关性研究进行综述,旨在为进一步研究提供思路。     

Unexpected uterine smooth muscle tumor of uncertain malignant potential and sarcoma: A single center cohort study in South Korea

ObjectiveTo evaluate the risk of encountering unexpected uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or sarcomas during surgical treatment of mesenchymal tumors of the uterus using morcellation.Material and methodsData were collected retrospectively from subjects who were pathologically diagnosed with uterine leiomyoma or its variants, STUMP or other premalignant mesenchymal tumors of uterus, or sarcoma during surgical treatment between July 2014 and June 2017.ResultsA total of 3785 women were investigated; 2824 laparoscopic procedures (74.6%) were performed, and an electronic power morcellator was used in 1636 patients (43.2%). Sixteen women (0.42%) were diagnosed with STUMP and 14 (0.37%) were diagnosed with uterine sarcoma. The incidence rate of unexpected STUMP or uterine sarcoma was 0.61% (23 of 3785 women); unexpected STUMP in 13 (0.34%), and unexpected sarcoma was in 10 (0.26%). Moreover, the unexpected leiomyosarcoma rate was 0.08% (3 in 3785). The rate of unintended morcellation of STUMPs was relatively high at 0.26% (10 in 3785), however, that for uterine sarcomas was 0.05% (2 in 3785).ConclusionThe risks of unintended morcellation were very low for sarcomas and STUMPs, although the risk of the latter was approximately 5-fold that of the former. To reduce the unintended dissemination of tumors, patients suspected of having malignancies should be provided adequate information regarding their treatment options as well as their associated risks. Meanwhile, improved preoperative screening methods for STUMP and sarcoma should be established.     

Plasticity of autonomic nerves: Differential effects of long-term guanethidine sympathectomy on the sensory innervation of the rat uterus during maturation

The sensory nerves, containing substance P and calcitonin gene-related peptide, and noradrenaline-containing sympathetic nerves of the rat uterus were analyzed following long-term sympathectomy with guanethidine in prepubertal (four weeks), young adult (eight weeks) and fully adult animals (18 weeks). Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows:

1. (1) long-term guanethidine treatment completely abolished the noradrenergic innervation of the uterine horn and parametrial tissue and markedly reduced the tissue levels of noradrenaline in both regions at the three ages analysed;

2. (2) in the uterine hom guanethidine treatment had no effect on the tissue levels of either calcitonin gene-related peptide or substance P or on the density of calcitonin gene-related peptide-containing nerves, at any of the three ages studied;

3. (3) in the parametrial tissue increased levels of calcitonin gene-related peptide were observed at 8 and 18 weeks of age, together with a significant increase in the density of calcitonin gene-related peptide-containing nerves.

Substance P levels showed a transient increase in this tissue at eight weeks. In conclusion, long-term sympathectomy with guanethidine resulted in an increase in calcitonin gene-related peptide and substance P in sensory nerves in the parametrial tissue, but not in the uterine horn. The changes in the parametrial tissue only occurred after puberty. It is suggested that sensory nerves in the uterine horn may be less responsive to sympathetic denervation since loss of sympathetic nerves occurs as part of a normal physiological process during pregnancy in this region.

子宫阔韧带肌瘤的CT诊断

目的　探讨子宫阔韧带肌瘤的CT诊断价值。方法　收集 2 1例子宫阔韧带肌瘤CT资料 ,进行回顾性分析 ,所有病例均经手术病理证实。结果　 2 1例均在盆腔内、子宫外显示肿块 ,CT表现 :实质性肿块 19例 ,边界清楚光整 16例 ,不甚清楚 3例 ,密度均匀 6例 ,平扫时与子宫肌密度相当 ,增强扫描呈明显强化 ,与子宫肌强化基本同步 ,不均匀 13例 ,其强化程度低于子宫肌 (约相差 10～ 2 0HU) ,瘤内变性、坏死或液化区不明显强化或不强化 ;囊实性 2例 ;肿块位置较固定 ,大多在宫旁匍匐生长 ,与子宫位置密切相关 ,其最大径层面与子宫体中心层面基本保持一致 ;形态各异 ,呈条块状、哑铃分叶状及扁圆烧饼状共 15例 ,呈圆形、椭圆形6例。结论　子宫旁呈条块、哑铃分叶状及扁圆烧饼状的实质性或实质性为主的肿块是本病较为可靠的CT征象 ,CT对诊断阔韧带肌瘤有实用价值     

阿胶补肾健骨方治疗去卵巢大鼠骨质疏松症的作用机制研究

目的：观察阿胶补肾健骨方对去卵巢大鼠骨质疏松症（OP）的影响,探讨阿胶补肾健骨方防治OP的作用机制。方法：将70只SD大鼠随机分为假手术组（J组）、模型组（M组）、阿胶补肾健骨方组（E组）和阿仑膦酸钠组（A组）。各组手术伤口恢复后,第7天开始灌胃（除J组外）治疗3个月,于末次给药后24 h处死大鼠并采集标本。采用ELISA法检测各组大鼠血清中OCN、PICP水平。结果：M组于造模后2个月起,体重明显高于J组（P＜0.05）;E组、A组体重渐增,显高于J组（P＜0.05）;M组、E组、A组大鼠子宫、双肾指数均不同程度均低于J组（P＜0.05);E组、A组大鼠子宫、双肾指数均高于M组（P＜0.05）;E组大鼠子宫、双肾指数优于A组（P＜0.05）;M组大鼠血清OCN、PICP均明显低于J组（P＜0.05）;E组、A组大鼠血清OCN、PICP水平均高于M组（P＜0.05）;A组大鼠血清OCN高于E组（P＜0.05）;E组大鼠血清PICP高于A组（P＜0.05）。结论：阿胶补肾健骨方可调节脂代谢,升高OP大鼠子宫及双肾指数;升高OP大鼠血清中OCN和PICP的水平,从而达到预防和治疗OP的目的。