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| 1 | 子宫内膜癌的治疗进展显示文摘子宫内膜癌(endometrial carcinoma,EC)是女性生殖系统最常见的三大恶性肿瘤之一,约占女性生殖系统恶性肿瘤的20%-30%,占女性全身恶性肿瘤的7%。子宫内膜癌好发于围绝经期及绝经后的妇女,近年来呈年轻化趋势,发生于绝经前的占25%,其中〈40岁占3%-14%。 | 公苓苓 郭杨 孙浩罡 王英红 | 2015 | 中国妇幼保健2015，30，11： | 37 |
| 2 | 子宫内膜癌及癌前病变第4版WHO的分类解读显示文摘子宫内膜癌在西方国家是女性最常见的恶性肿瘤,随着我国经济的发展,人们生活水平的提高,肥胖及代谢性疾病的增加,子宫内膜癌的发病率也呈逐年增高的趋势,已经成为女性生殖系统第二大常见恶性肿瘤。众所周知,子宫内膜癌并不是一个单一的肿瘤,它是由生物学和组织学各异的一组肿瘤组成, | 沈丹华 | 2015 | 实用妇产科杂志2015，31，7： | 16 |
| 3 | 子宫内膜癌组织中ER、PR、p53、Ki-67的表达及其与临床病理特征的相关性分析显示文摘子宫内膜癌(endometrial carcinoma)是女性最常见的生殖系统恶性肿瘤之一,其发病率逐年增高,且有年轻化趋势。子宫内膜癌的发病机制尚未完全清楚,但临床大量研究已经证实性激素水平异常可能是导致子宫内膜癌发病的主要原因之一,同时抑癌基因的抑制、原癌基因的激活等也参与了子宫内膜癌的发生发展过程。 | 赵琦 | 2017 | 中国实验诊断学2017，21，2： | 16 |
| 4 | Role of phosphatase PTEN in the activation of extracellular signal-regulated kinases induced by estradiol in endometrial carcinoma cells显示文摘Objectives To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-β-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs. Methods Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-β-estradiol for different lengths of time. Western blot was also used for examining the expression of ERα and ERβ in NIH3T3 fibroblasts after transient transfection of pCXN2hERα and pCXN2hERβ. Then, ERK activation was examined after stimulation with 17-β-estradiol. Results 17-β-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-β-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-β-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-β-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERα. Conclusions 17-β-estradiol activate ERK cascades in Ishikawa cells by integrating with ERα. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-β-estradiol in Ishikawa cells. | 张育军 魏丽惠 王建六 孙铁铮 | 2003 | Chinese Medical Journal2003，，3： | 13 |
| 5 | DNMT3A/3B overexpression might be correlated with poor patient survival, hypermethylation and low expression of ESR1/PGR in endometrioid carcinoma: an analysis of The Cancer Genome Atlas显示文摘Background:DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial cancer.ESR1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain tumors.However, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied extensively.The aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer to investigate whether the methylation catalyzed by DNMT3A/3B contributes to low ER/PR expression.Methods:The clinicopathologic information and RNA-Seq expression data of DNMT3A/3B of 544 endometrial cancers were derived from The Cancer Genome Atlas (TCGA) uterine cancer cohort in May 2018.RNA-Seq level of DNMT3A/3B was compared between these clinicopathologic factors with t-test or one-way analysis of variance.Results:DNMT3A/3B was overexpressed in endometrioid carcinoma (EEC) and was even higher in non-endometrioid carcinoma (NEEC) (DNMT3A, EEC vs.NEEC:37.6% vs.69.9%, t=-7.440, P<0.001;DNMT3B, EEC vs.NEEC:42.4% vs.72.8 %, t=-6.897, P<0.001).In EEC, DNMT3A overexpression was significantly correlated with the hypermethylation and low expression of the ESR1 and PGR (P<0.05).The same trend was observed in the DNMT3B overexpression subgroup.In the ESR1/PGR low-expression subgroups, as much as 83.1% of ESR1 and 59.5% of PGR were hypermethylated, which was significantly greater than the ESR1/PGR high-expression subgroups (31.3% and 11.9%, respectively).However, the above phenomena were absent in NEEC, while DNMT3A/3B overexpression, ESR1/PGR hypermethylation, and low ER/PR expression occurred much more often.In univariate analysis, DNMT3A/3B overexpressions were significantly correlated with worse prognosis.In multivariate analysis, only DNMT3A was an independent predictor of disease-free survival (P<0.05).Conclusions:DNMT3A/3B expression increases progressively from EEC to NEEC and is correlated with poor survival.The mechanisms underlying low ER/PR expression might be distinct in EEC vs.NEEC.In EEC, methylation related to DNMT3A/3B overexpression might play a major role in ER/PR downregulation. | Dan He Xiao Wang Yan Zhang Jian Zhao Rui Han Ying Dong | 2019 | Chinese Medical Journal2019，，2： | 12 |
| 6 | IL-10、IL-17在子宫内膜癌中的表达及其与临床病理的关系显示文摘子宫内膜癌(endometrial carcinoma)作为临床常见的妇科恶性肿瘤,多发生于50岁及以上的绝经妇女,并且其发病率有呈逐渐升高的趋势,严重威胁患者的健康和生命质量。关于其发病机制,目前尚无统一结论 ,有研究证实多种细胞因子可能参与了子宫内膜癌的发生及发展过程。 | 欧阳小明 史文静 冀天星 郝卓芳 廖德贵 | 2015 | 中国实验诊断学2015，19，5： | 12 |
| 7 | Antidiastole Value of Three-dimensional Ultrasonography and Power Doppler between Uterine Parenchyma Lumps and Endometrial Cancer:A Retrospective Study显示文摘Sometimes endometrial polyps,submucosal myomas,and endometrial cancer show similar findings under ultrasonography.The aim of this study was to assess the antidiastole value of blood flow parameters using three-dimensional(3D)power Doppler ultrasonography angiography(PDA)between endometrial cancer and uterine parenchyma lumps.The data of the blood flow indices in 3D-PDA including the vascularization index(VI),flow index(FI),and vascularization flow index(VFI)in 40 patients with endometrial cancer and 41 patients with uterine parenchyma lumps(endometrial polyps and submucosal myomas)were retrospectively analysed and compared utilizing Virtual Organ Computer-aided AnaLysis(VOCAL)software.The results showed that all the blood flow parameters(VI,FI,VFI)were significantly higher in women with endometrial cancer than in those with uterine parenchyma lumps(P<0.001).The area under the curve of ROC of VI,FI,and VFI was 0.98,0.84,and 0.97,respectively.Thus,the best predictor of endometrial carcinoma was VI with a sensitivity of 97.0% and a specificity of 91.0%.The optimal cutoff value of VI was 4.06%.Our data demonstrated that all of the blood flow signal parameters(including VI,FI,and VFI)in 3D power Doppler ultrasonography had significant antidiastole values between endometrial cancer and uterine parenchyma lumps to assist clinicians in properly diagnosing patients. | Yan ZHANG Jing CHEN Zeng ZHEN Xiao-yan XU | 2019 | Current Medical Science2019，39，5： | 11 |
| 8 | 快速冰冻病理在98例子宫内膜癌手术中的临床价值显示文摘子宫内膜癌(endometrial carcinoma)是女性生殖器官常见的恶性肿瘤之一,近年来其发病率呈上升趋势。本文通过回顾性分析我院98例子宫内膜癌患者术中快速冰冻病理检查,并根据子宫内膜癌的特殊病理类型、肿瘤细胞分级及癌灶肌层浸润深度的相符情况,旨在讨论快速冰冻病理在子宫内膜癌术中行分期手术的临床价值。 | 张秀平 | 2016 | 中国药物与临床2016，16，3： | 10 |
| 9 | SCM-198 protects endometrial stromal cells from oxidative damage through Bax/Bcl-2 and ERK signaling pathways显示文摘In creasi ng amounts of evidence dem on strated that accumulative reactive oxyge n species (ROS) and apoptosis of human endometrial stromal cells (ESCs) are closely associated with endometrial dysfunction induced by oxidative stress, which plays an important role in the pathological process of multiple gyn ecological and reproduction-related diseases. SCM-198, an alkaloid active component of Leonurus japonicas Houtt, has been reported to have anti-oxidative activity. However, the specific mechanisms of SCM-198 in the prevention of endometrial damage remain unknown. In the present study, we assessed the effect of SCM-198 on hydrogen peroxide (H2O2Hnduced oxidative injury in ESCs. ESCs were pretreated with SCM-198 for 4 h and then challenged with H2O2.Morphology ch a nges, apoptosis rate, and intracellular ROS producti on were measured to assess the level of oxidative injury. Flow cytometry and western blot analysis were performed to detect the expression levels of Bax, Bcl-2, active-caspase-3, and mitogen-activated protein kinases pathways. Classic inflammation cytokines were measured by real-time polymerase chain reactions. Our results showed that SCM-198 attenuated apoptosis and ROS generation of ESCs induced by H2O2. H2O2 induced the apparent apoptotic characteristics, including fragmentation of DNA, upregulation of Bax/Bcl2, activation of caspase-3, and secretion of inflammation cytokines, which were all ameliorated by SCM-198. Furthermore, H2O2-induced apoptosis-related ERK1/2 pathway activation was restrained by SCM-198 pretreatme nt. These fin dings suggested that SCM-198 could protect ESCs from oxidative injury, mainly by inhibiting oxidative stress and reducing apoptosis. | Yunyun Li Yikong Lin Xixi Huang Chunfang Xu Xinhua Liu Li Wang Min Yu Dajin Li Yizhun Zhu Meirong Du | 2019 | Acta Biochimica et Biophysica Sinica2019，51，6： | 10 |
| 10 | Endometrial mesenchymal stem cells as a cell based therapy for pelvic organ prolapse显示文摘Pelvic organ prolapse(POP) occurs when the pelvic organs(bladder, bowel or uterus) herniate into the vagina, causing incontinence, voiding, bowel and sexual dysfunction, negatively impacting upon a woman's quality of life. POP affects 25% of all women and results from childbirth injury. For 19% of all women, surgical reconstructive surgery is required for treatment, often augmented with surgical mesh. The surgical treatment fails in up to 30% of cases or results in adverse effects, such as pain and mesh erosion into the bladder, bowel or vagina. Due to these complications the Food and Drug Administration cautioned against the use of vaginal mesh and several major brands have been recently been withdrawn from market. In this review we will discuss new cell-based approaches being developed for the treatment of POP. Several cell types have been investigated in animal models, including a new source of mesenchymal stem/stromal cells(MSC) derived from human endometrium. The unique characteristics of endometrial MSC, methods for their isolation and purification and steps towards their development for good manufacturing practice production will be described. Animal models that could be used to examine the potential for this approach will also be discussed as will a rodent model showing promise in developing an endometrial MSC-based therapy for POP. The development of a preclinical large animal model for assessing tissue engineering constructs for treating POP will also be mentioned. | Stuart J Emmerson Caroline E Gargett | 2016 | World Journal of Stem Cells2016，8，5： | 10 |
| 11 | Activation of Rev-erbα attenuates lipopolysaccharide-induced inflammatory reactions in human endometrial stroma cells via suppressing TLR4-regulated NF-κB activation显示文摘Perturbation of the circadian rhythm damages the biological characteristics of cells and leads to their dysfunction. Rev-erbα, an important gene in the transcription-translation loop of circadian rhythm, is involved in regulating the balance between pro-inflammation and anti-inflammation. The disruption of this balance in human endometrial stroma cells (hESCs) destroys their biological behavior function in maintaining the menstrual cycle and embryonic implantation. Whether pharmacological modulation of Rev-erbα affects the inflammation of hESCs remains unclear. In this study, we treated hESCs with lipopolysaccharide (LPS) and found that LPS treatment increased the mRNA levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, IL-18, and TNFα, and the secretion of IL-6. SR9009, a Rev-erbα agonist, significantly alleviated the LPS-induced production of pro-inflammatory cytokines in hESCs. Meanwhile, knockdown of Rev-erbα increased the expressions of IL-1β, IL-6, and IL-8, accompanied by an increased mRNA level of the core clock gene Bmal1. Western blot analysis showed that SR9009 inhibited the expression of toll-like receptor 4 (TLR4) and the activation of NF-κB induced by LPS. All these findings suggested that pharmacological activation of Rev-erbα attenuated the LPS-induced inflammatory response of hESCs by suppressing TLR4-regulated NF-κB activation. This study may provide a strategy for preventing inflammation-related endometrial dysfunction and infertility or recurrent implantation failure. | Weijie Zhao Liyuan Cui Xixi Huang Songcun Wang Dajin Li Liping Li Yan Sun Meirong Du | 2019 | Acta Biochimica et Biophysica Sinica2019，51，9： | 8 |
| 12 | Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer显示文摘Obesity is a global pandemic characterized by high levels of body fat(adiposity) and derived-cytokines(i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin's main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1(IL-1) [Notch, IL-1 and leptin crosstalk outcome(NILCO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILCO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILCO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers. | Crystal C Lipsey Adriana Harbuzariu Danielle Daley-Brown Ruben R Gonzalez-Perez | 2016 | World Journal of Methodology2016，6，1： | 8 |
| 13 | Analyses of circRNA profiling during the development from pre-receptive to receptive phases in the goat endometrium显示文摘Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes.Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5(pre-receptive endometrium,PE) and three goats at gestational day 15(receptive endometrium,RE).Overall,21,813 circRNAs were identified,of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE,which suggested high stage-specificity.Further analysis found 334 differentially expressed circRNAs in the RE compared with PE(P < 0.05).The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression.Moreover,some circRNAs were regulated by estrogen(E2)/progesterone(P4) in endometrial epithelium cell lines(EECs) and endometrial stromal cell line(ESCs),and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4.Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation. | Yuxuan Song Lei Zhang Xiaorui Liu Mengxiao Niu Jiuzeng Cui Sicheng Che Yuexia Liu Xiaopeng An Binyun Cao | 2019 | Journal of Animal Science and Biotechnology2019，10，3： | 8 |
| 14 | Wogonoside inhibits tumor growth and metastasis in endometrial cancer via ER stress-Hippo signaling axis显示文摘Wogonoside,a bioactive flavonoid component derived from Scutellaria baicalensis Georgi,has been reported to inhibit tumor growth in mice bearing various types of cancer cells such as breast cancer,lung cancer,and leukemia cells.However,whether wogonoside could inhibit tumor growth of endometrial cancer has not been elucidated.In this study,we explored the function of wogonoside on tumor growth and the underlying mechanism on endometrial cancer.Firstly,we investigated the effect of wogonoside on endometrial cancer cells and found that wogonoside could significantly decrease cell proliferation and metastasis.Mechanistically,wogonoside could aggravate the extent of ER stress and upregulate the phosphorylation level of Mammalian Ste20-like kinase 1,leading to the activation of the Hippo signaling pathway.Taken together,in vitro and in vivo data demonstrated that wogonoside could be a potent inducer of ER stress and could be further developed into a promising therapy for endometrial cancer. | Shaorong Chen Zhuna Wu Yumin Ke Pingping Shu Caihong Chen Ruying Lin Qirong Shi | 2019 | Acta Biochimica et Biophysica Sinica2019，51，11： | 8 |
| 15 | Effect of Danzhi decoction on expression of angiogenesis factors in patients with sequelae of pelvic inflammatory disease显示文摘Objective:To investigate the efteets of traditional Chinese medicine.Danzhi decoction,on the expression angiogenesis factors in human endometrial cells during the sequelae of pelvic inflammatoty disease(SPID) and explore the role of Danzhi decction in improving the blood stasis microenvironment of SPID.Methods:A three-dimensional(3D) co—culture system including human vascular endothelial cells(VECs),endometrial stromal cells and glandular epithelial cells was established in vitro and treated with Danzhi decoction,sterilized water and aspirin respectively.A Milliplex multifunctional liquid chip technique was used to measure the expression levels of vascular endothelial growth factor(VEGF)—A/C/D,fibroblast growth factor-1/2.angiopoietin-2.epidermal growth factor(EGF) HB-EGF,bone morphogenetic protein-9.endoglin.endothehn-l.granulocyte colony stimulating factor,hepatocyte growth factor,interleukin-8,follistatin.placenta growth factor and leptin.The location of angiogenesis factors was monitored by immunofluorescence labeling and confocal laser scanning microscope3 D reconstruction.Results:Endometrial stromal cells and glandular epithelial cells were isolated and primary cultured for establishing a 3D co-culture system.The levels of VEGF—A/C/D in Danzhi decoction group and aspirin group were significantly lower than those in mock group(P<0.05).while there was no significant difference between Danzhi decoction group and aspirin group(P>0.05).Furthermore,the alterative location of VEGF—A/C/D was observed in the cytoplasm of endometrial glandular epithelial cells.Conclusions:Danzhi decoction mav inhibit the expression of VEGF in the blood stasis microenvironment of SPID by targeting the cytoplasm of endometrial glandular epithelial cell. | Bao-Qin Liu Xin Gong Zhe Jin | 2014 | Asian Pacific Journal of Tropical Medicine2014，7，12： | 7 |
| 16 | Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways显示文摘Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways. | Wenyan Tian Fei Teng Jinping Gao Chao Gao Guoyan Liu Yanfang Zhang Shizhu Yu Wei Zhang Yingmei Wang Fengxia Xue | 2019 | Cancer Biology & Medicine2019，16，1： | 6 |
| 17 | miR-27b-3p/MARCH7 regulates invasion and metastasis of endometrial cancer cells through Snail-mediated pathway显示文摘Ubiquitin E3 ligase membrane-associated RING-CH-type finger 7(MARCH7),also known as axotrophin,was originally identified in mouse embryonic stem cells.MARCH7 is involved in T-cell proliferation,neuronal development,and the immune system.However,its role in endometrial cancer(EC)remains unclear.This study aimed to investigate the role of MARCH7 in EC.Quantitative polymerase chain reaction,immunohistochemistry,and western blot analysis were used to examine the expression of MARCH7,E-cadherin,Snail,and Vimentin in EC cell lines or clinical specimens.The role of MARCH7 in maintaining EC cell malignant phenotype was determined by transwell assay and using xenograft tumor model.Dual-luciferase reporter gene assay was performed to determine whether MARCH7 is an authentic target of miR-27b-3p.Our data showed that the expression level of MARCH7 in EC tissues was higher than that in normal endometrium tissues.The level of MARCH7 was positively associated with that of Snail and Vimentin,clinical stage,and histological grade,while negatively associated with that of E-cadherin.Knockdown of MARCH7 inhibited the invasion and metastasis of EC cells in vitro and in vivo.The opposite effect was observed after overexpressing MARCH7.MARCH7 promoted invasion and metastasis of EC cells via the Snail-mediated pathway.Furthermore,MARCH7 was demonstrated to be an authentic target of miR-27b-3p,and miR-27b-3p decreased the stimulus effect induced by MARCH7.These data indicate that MARCH7 may be an oncogenic factor and a therapeutic target for EC.miR-27b-3p/MARCH7 may also regulate EC cell invasion and metastasis via the Snail-mediated pathway. | Ling Liu Jianguo Hu Tinghe Yu Shuang You Yulin Zhang Lina Hu | 2019 | Acta Biochimica et Biophysica Sinica2019，51，5： | 6 |
| 18 | 超声引导下聚桂醇硬化治疗在复发性卵巢巧克力囊肿中的应用显示文摘卵巢子宫内膜异位囊肿(ovarian endometrial cyst,OEC)又称卵巢巧克力囊肿,是子宫内膜异位症中最常见的一种病变,约占80%,多发于育龄期妇女。临床上多使用药物治疗及手术治疗,但长期使用药物不良反应较大,而保守性手术对患者损伤较大,且难以彻底治愈,术后极其容易复发,复发率约为24.1%~57.1%[1]。而复发性卵巢巧克力囊肿目前尚无特别有效的治疗方法。 | 王丹 何冠南 | 2017 | 山西医药杂志2017，46，11： | 6 |
| 19 | Leptin-induced Notch and IL-1 signaling crosstalk in endometrial adenocarcinoma is associated with invasiveness and chemoresistance显示文摘BACKGROUND Obesity is a recognized risk factor for endometrial cancer (EmCa) and other cancer types. Leptin levels are significantly increased in obese individuals. Leptin-induced signaling crosstalk [Notch, Interleukin-1 (IL-1) and leptin outcome, NILCO] has been associated with breast cancer progression. This complex signaling crosstalk affects cancer cell proliferation, migration, invasion, angiogenesis, apoptosis and chemoresistance. NILCO expression was previously detected in human EmCa. However, it is unknown whether leptin regulates NILCO and alters EmCa’s response to chemotherapeutics. It is hypothesized that leptin induces NILCO and increases aggressiveness and chemoresistance in EmCa cells. AIM To determine whether leptin induces NILCO molecules in EmCa affecting cell proliferation, aggressiveness and chemoresistance. METHODS Leptin’s effects on the expression of NILCO molecules [mRNAs and proteins for Notch receptors (Notch1-4), ligands (JAG1 and DLL4) and downstream effectors (survivin, Hey2), and leptin (OB-R) and IL-1 (IL-1R tI) receptors] was examined in EmCa cells (type I: Ishikawa, and HEC-1A, and type II: An3Ca and KLE) using Real-time PCR and Western blot analysis, respectively. In addition, the effects of leptin on cell cycle, proliferation and cell invasion were determined using cytometric analysis (Cellometer Vision CBA system), MTT cell proliferation and Matrigel-based invasion assays, respectively. Inhibitors of leptin (nanoparticlebound leptin peptide receptor antagonist-2, IONP-LPrA2), IL-1 (anti-IL-1R tI antibody) and Notch (siRNA interference RNA) were used to investigate NILCO’s effects on cell proliferation and invasion. Leptin’s effects on Paclitaxel cytotoxicity in EmCa cells was determined by the CCK8 and Cellometer-based Annexin V assays. RESULTS For the first time it was shown that leptin is an inducer of Notch in EmCa. Experimental data suggest that leptin induced the expression of NILCO molecules, promoted proliferation and S- phase progression, and reduced Paclitaxel cytotoxicity on EmCa cells. Leptin’s effects were higher in type II EmCa cells. The progression of this more aggressive form of the disease is associated with obesity. Remarkably, the use of the leptin signaling antagonist, IONPLPrA2, re-sensitized EmCa cells to Paclitaxel. CONCLUSION Present data suggest the notion that leptin-induced NILCO could be a link between obesity and EmCa progression and chemoresistance. Most aggressive type II EmCa cells were higher sensitive to leptin, which appears to increase proliferation, cell cycle progression, aggressiveness, and chemoresistance to Paclitaxel. Therefore, leptin and NILCO could be novel therapeutic targets for type II EmCa, which does not have targeted therapy. Overall, IONP-LPrA2 has a potential as a novel adjuvant drug to enhance the effectiveness of type II EmCa chemotherapy. | Danielle Daley-Brown Adriana Harbuzariu Ann Anu Kurian Gabriela Oprea-Ilies Ruben Rene Gonzalez-Perez | 2019 | World Journal of Clinical Oncology2019，10，6： | 5 |
| 20 | Sonohysterography: Principles, technique and role in diagnosis of endometrial pathology显示文摘Sonohysterography (SHG), which provides enhanced endometrial visualization during standard transvaginal ultrasonography, is a relatively safe procedure for the evaluation of endometrial pathology. It can be used to evaluate patients with abnormal vaginal bleeding or infertility. This modality offers real time imaging of the endometrium without exposure to ionizing radiation. SHG is typically used in patients for whom standard transvaginal ultrasonography does not show the endometrium well, show a potential abnormality for which further imaging is required, or in patients without endometrial pathology defined on routine transvaginal imaging but in whom there is a strong clinical suspicion of an abnormality. This article will discuss the utility of the sonohysterogram in evaluation of various endometrial pathologies. Imaging examples of these pathological entities will be illustrated as well. | Thomas Yang Amit Pandya Leonardo Marcal Ronald O Bude Joel F Platt Deepak G Bedi Khaled M Elsayes | 2013 | World Journal of Radiology2013，5，3： | 5 |
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