Publications by authors named "Fengxia Xue"

89 Publications

Endometrial cancer in Lynch syndrome.

Int J Cancer 2021 Aug 16. Epub 2021 Aug 16.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.
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http://dx.doi.org/10.1002/ijc.33763DOI Listing
August 2021

Evaluation of the practical applications of fluorescence hybridization in the prenatal diagnosis of positive noninvasive prenatal screenings.

J Matern Fetal Neonatal Med 2021 Jul 21:1-8. Epub 2021 Jul 21.

Department of Obstetrics & Gynecology, Tianjin Medical University General Hospital, Tianjin, China.

Objective: To investigate the application value and limitations of fluorescence hybridization (FISH) in prenatal diagnosis of positive results for trisomies 13, 18, 21 (T13, T18, T21) and sex chromosome aneuploidies (SCAs) indicated by noninvasive prenatal screening (NIPS).

Methods: Samples from women who underwent prenatal diagnosis for the indication of positive NIPS of T13, T18, T21, and SCAs were collected. Each sample was split into two for both karyotype analysis and FISH analysis. The efficiency and consistency of FISH were assessed for the detection of chromosome abnormalities in the indications of positive NIPS results compared with karyotyping.

Results: A total of 649 pregnant women who scored positive for clinical significance of fetal chromosome abnormalities by NIPS were enrolled in our study, including T 13 (6%), T18 (14.3%), T21 (44.7%), SCAs (35.0%). From the following diagnostic test, the positive predictive value (PPV) of NIPS for T13, T18, T21, and SCAs was 17.9, 60.2, 89.3, and 43.6% respectively. FISH analysis was successful in all samples. Compared with karyotyping, the sensitivity and specificity were 98.3 and 100%, respectively. 95.7% (621/649) were fully concordant with karyotyping. 3.2% (21/649) cases were incompletely concordant with the karyotyping, among these cases, the FISH analysis identified all the aneuploidies, but karyotyping analysis provided more information about the chromosomal structure. There were 7 cases (1.1%, 7/649) of anomalies diagnosed by karyotype but missed out by FISH, all of which occurred in cases with the indication of SCAs. If the indications were confined to cases with a positive NIPS of T13, T18, T21, the diagnostic consistency of the two methods almost perfectly agree, and all the aneuploidies were detected by the FISH assay. FISH analysis was highly consistent in determining whether the fetus was euploid or not in the prenatal diagnosis for the patients with positive NIPS results compared with karyotyping (kappa= 0.976,  < .01).

Conclusion: For the prenatal diagnostic indications of positive NIPS of T13, T18, T21, and SCAs, FISH was equally efficacious in identifying aneuploidies and provided a quick diagnosis to alleviate anxiety. However, the missed risk of FISH analysis for structural chromosomal abnormalities should be taken seriously and fully informed during genetic counseling.
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http://dx.doi.org/10.1080/14767058.2021.1949449DOI Listing
July 2021

Weight Loss Improves Pregnancy and Livebirth Outcomes in Young Women with Early-Stage Endometrial Cancer and Atypical Hyperplasia.

Cancer Manag Res 2021 14;13:5711-5722. Epub 2021 Jul 14.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Key laboratory of Female Reproductive Health and Eugenics, Tianjin, People's Republic of China.

Purpose: To evaluate the effects of body weight loss on reproductive outcomes in young women with early-stage endometrial cancer (EC) and atypical hyperplasia (AH) who underwent fertility-sparing therapy.

Patients And Methods: Patients with well-differentiated EC (n=8, FIGO stage Ia) and AH (n=36) who achieved complete regression after fertility-sparing therapy were retrospectively reviewed. Patients were divided into a weight loss group (n=25) and a non-weight loss group (n=19). Subgroup analysis according to body mass index and relative weight loss were performed to investigate the effect of weight loss on pregnancy and live birth outcomes. Univariate and multivariate logistic regression analyses were undertaken to determine pregnancy-associated factors.

Results: Mean body weight and body mass index at pre-progestin treatment and at fertility treatment initiation were 70.63±12.03 and 67.08±8.18 kg, respectively, 27.06±4.44 and 25.73±3.15 kg/m, respectively. Twenty-five patients (56.82%) lost weight, the median absolute weight loss was 5.00 kg (1.00-34.50), and the median relative weight loss was 6.70% (1.00-36.00%) over a median of 12 months (5.00-97.00). A favorable pregnancy rate (65.91%) and live birth rate (50.00%) were achieved. The pregnancy and live birth rates were meaningfully higher in the weight loss group than in the non-weight loss group (88.00% vs 36.84%, =0.000; 64.00% vs 31.58%, =0.033); weight loss ≥5% significantly increased pregnancy and live birth rate in patients with BMI ≥25 kg/m. The risk ratio of weight loss ≥5% in multivariate logistic analysis for pregnancy was 10.448 (1.102, 99.056, =0.041).

Conclusion: Weight loss could positively affect pregnancy rate and improve live birth rate in overweight and obese women with early-stage EC and AH during/after fertility-sparing therapy. Weight loss ≥5% increased pregnancy and livebirth rates significantly in overweight and obese women.
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http://dx.doi.org/10.2147/CMAR.S316040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286730PMC
July 2021

IK: A novel cell mitosis regulator that contributes to carcinogenesis.

Cell Biochem Funct 2021 Jul 11. Epub 2021 Jul 11.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Carcinogenesis is characterized by abnormal regulation of cell growth and cell death. IK is a novel cell mitosis regulator that may contribute to carcinogenesis. Previous studies showed that the loss of IK expression resulted in cell mitotic arrest and even cell death. Besides, IK can also inhibit the interferon gamma (IFN-γ)-induced expression of human leukocyte antigen (HLA) class II antigen, which is associated with tumour immune microenvironment. To gain insight into the current research progress regarding IK, we conducted a review and searched the limited literature on IK using PubMed or Web of Science. In this review, we discussed the possible biological functions and mechanisms of IK in cancer and its immune microenvironment. Future perspectives of IK were also mentioned to explore its clinical significance.
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http://dx.doi.org/10.1002/cbf.3660DOI Listing
July 2021

Inactivating Mutations of the Gene Weaken Ku80/Ku70-Mediated DNA Repair and Sensitize Endometrial Cancer to Chemotherapy.

Cancers (Basel) 2021 May 20;13(10). Epub 2021 May 20.

Department of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.

IK is a mitotic factor that promotes cell cycle progression. Our previous investigation of 271 endometrial cancer (EC) samples from the Cancer Genome Atlas (TCGA) dataset showed IK somatic mutations were enriched in a cluster of patients with high-grade and high-stage cancers, and this group had longer survival. This study provides insight into how IK somatic mutations contribute to EC pathophysiology. We analyzed the somatic mutational landscape of IK gene in 547 EC patients using expanded TCGA dataset. Co-immunoprecipitation and mass spectrometry were used to identify protein interactions. In vitro and in vivo experiments were used to evaluate IK's role in EC. The patients with IK-inactivating mutations had longer survival during 10-year follow-up. Frameshift and stop-gain were common mutations and were associated with decreased IK expression. IK knockdown led to enrichment of G2/M phase cells, inactivation of DNA repair signaling mediated by heterodimerization of Ku80 and Ku70, and sensitization of EC cells to cisplatin treatment. IK/Ku80 mutations were accompanied by higher mutation rates and associated with significantly better overall survival. Inactivating mutations of IK gene and loss of IK protein expression were associated with weakened Ku80/Ku70-mediated DNA repair, increased mutation burden, and better response to chemotherapy in patients with EC.
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http://dx.doi.org/10.3390/cancers13102487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160817PMC
May 2021

Antibiotic prescriptions for children younger than 5 years with acute upper respiratory infections in China: a retrospective nationwide claims database study.

BMC Infect Dis 2021 Apr 12;21(1):339. Epub 2021 Apr 12.

National Clinical Research Center for Respiratory Diseases, Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: In China, there were few studies to estimate antibiotic use for children with upper respiratory infections at the national level. The aim of this study was to describe the antibiotic prescribing practice for children aged < 5 years old with upper respiratory infections (URIs) using a nationwide claims database.

Methods: This was a retrospective cross-sectional study using a sampled database from the China Health Insurance Research Association (CHIRA). Study subjects included children younger than 5 years with outpatient visits in 2015 that resulted in a diagnosis of a upper respiratory infection. We calculated the percentage of visits who received antibiotics, the proportion of injection formulations, the percentage of combined antibiotics and the proportion of each antibiotic class. The patterns of antibiotic prescription were also described by medical institution type, city level and geographical region.

Results: Among the 92,821 visits, 27.1% were prescribed antibiotics, of which 27.0% received injection formulations. The rate of antibiotic prescribing varied by age group (P < 0.001), with the lowest (16.0%) in infants and the highest in patients at age 3 to < 4 years (29.9%) and age 4 to < 5 years (32.5%). The Midwestern region, underdeveloped cities and low-level hospitals represented relatively higher rates of prescribing antibiotics (P < 0.001) and higher proportions of injection dosage forms (P < 0.001). The most 3 common antibiotic classes prescribed of all visits with antibiotic prescriptions were the third-generation cephalosporins (34.9%), macrolides (24.3%), and the second-generation cephalosporins (23.3%).

Conclusions: In mainland China, the overall rate of antibacterial prescribing and the proportion of injection formulations prescribed in children under 5 years with URIs were at a low level, but still higher in underdeveloped regions and cities. Moreover, the overuse of the second and third generation cephalosporins, macrolides, remains a serious issue. Further efforts should be focused on reducing those non-first-line antibiotic prescribing and narrowing the gaps among regions and cities.
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http://dx.doi.org/10.1186/s12879-021-05997-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040226PMC
April 2021

Harmine alleviates atherogenesis by inhibiting disturbed flow-mediated endothelial activation via protein tyrosine phosphatase PTPN14 and YAP.

Br J Pharmacol 2021 04 15;178(7):1524-1540. Epub 2021 Feb 15.

Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.

Background And Purpose: Disturbed flow induces endothelial dysfunction and contributes to uneven distribution of atherosclerotic plaque. Emerging evidence suggests that harmine, a natural constituent of extracts of Peganum harmala, has potent beneficial activities. Here, we investigated if harmine has an atheroprotective role under disturbed flow and the underlying mechanism.

Experimental Approach: Mice of ApoE , LDLR , and endothelial cell (EC)-specific overexpression of yes-associated protein (YAP) in ApoE background were fed with a Western diet and given harmine for 4 weeks. Atherosclerotic lesion size, cellular composition, and expression of inflammatory genes in the aortic roots were assessed. HUVECs were treated with oscillatory shear stress (OSS) and harmine and also used for proteomic analysis.

Key Results: Harmine retarded atherogenesis in both ApoE and LDLR mice by inhibiting the endothelial inflammatory response. Mechanistically, harmine blocked OSS-induced YAP nuclear translocation and EC activation by reducing phosphorylation of YAP at Y357. Overexpression of endothelial YAP blunted the beneficial effects of harmine in mice. Proteomic study revealed that protein tyrosine phosphatase non-receptor type 14 (PTPN14) could bind to YAP. Moreover, harmine increased PTPN14 expression by stabilizing its protein level and inhibiting its degradation in proteasomes. PTPN14 knockdown blocked the effects of harmine on YAP and EC activation. Finally, overexpression of PTPN14 mimicked the effects of harmine and ameliorated atherosclerosis, and knockdown of PTPN14 blunted the atheroprotective effects of harmine and accelerated atherosclerosis, in a partial ligation mouse model.

Conclusion And Implications: Harmine alleviated OSS-induced EC activation via a PTPN14/YAP pathway and had a potent atheroprotective role.
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http://dx.doi.org/10.1111/bph.15378DOI Listing
April 2021

The Interaction Between Microorganisms, Metabolites, and Immune System in the Female Genital Tract Microenvironment.

Front Cell Infect Microbiol 2020 23;10:609488. Epub 2020 Dec 23.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

The female reproductive tract microenvironment includes microorganisms, metabolites, and immune components, and the balance of the interactions among them plays an important role in maintaining female reproductive tract homeostasis and health. When any one of the reproductive tract microorganisms, metabolites, or immunity is out of balance, it will affect the other two, leading to the occurrence and development of diseases and the appearance of corresponding symptoms and signs, such as infertility, miscarriage, premature delivery, and gynecological tumors caused by infectious diseases of the reproductive tract. Nutrients in the female reproductive tract provide symbiotic and pathogenic microorganisms with a source of nutrients for their own reproduction and utilization. At the same time, this interaction with the host forms a variety of metabolites. Changes in metabolites in the host reproductive tract are related not only to the interaction between the host and microbiota under dysbiosis but also to changes in host immunity or the environment, all of which will participate in the pathogenesis of diseases and lead to disease-related phenotypes. Microorganisms and their metabolites can also interact with host immunity, activate host immunity, and change the host immune status and are closely related to persistent genital pathogen infections, aggravation of infectious diseases, severe pregnancy outcomes, and even gynecological cancers. Therefore, studying the interaction between microorganisms, metabolites, and immunity in the reproductive tract cannot only reveal the pathogenic mechanisms that lead to inflammation of the reproductive tract, adverse pregnancy outcomes and tumorigenesis but also provide a basis for further research on the diagnosis and treatment of targets.
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http://dx.doi.org/10.3389/fcimb.2020.609488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785791PMC
June 2021

Discovery of a Chinese familial deletion 18p syndrome due to a false positive result on noninvasive prenatal testing.

J Obstet Gynaecol Res 2021 Feb 16;47(2):827-832. Epub 2020 Nov 16.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Clinical manifestations of deletion 18p syndrome vary a lot, which makes it easily overlooked in the clinical practice. Familial transmission of deletion 18p syndrome is rare. We report a Chinese familial deletion 18p syndrome, which was diagnosed by anatomizing the underlying reason for the discrepancy between noninvasive prenatal testing (NIPT) and prenatal diagnosis. A 35-year-old pregnant woman was recruited to our center owing to the abnormal NIPT result with a high risk of chromosome 18 monosomy. However, the karyotype of the fetus was normal after amniocentesis. Further analysis indicated that the pregnant woman herself had an abnormal karyotype of 46,XX,del(18)(p11.2), (arr18p11.32p11.21[136,227-15,099,116]×1) and her first 12-year-old son had got the same deletion of 18p as her. A distinct phenotype variability was noted although they share identical deletion. We consider that adequate clinical genetic counseling is vital for women with adverse pregnancy history before getting pregnant. Maternal CNVs may be one of the main causes of the false-positive result on NIPT. NIPT, especially extended NIPT may provide extra valuable evidence when used as routine prenatal screening method.
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http://dx.doi.org/10.1111/jog.14565DOI Listing
February 2021

The oncogenic role of SOX8 in endometrial carcinoma.

Cancer Biol Ther 2020 12 16;21(12):1136-1144. Epub 2020 Nov 16.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital , Tianjin, China.

Endometrial carcinoma (EC) remains one of the most prevalent forms of cancer to impact the female reproductive system, yet the mechanisms governing its development and progression are incompletely understood. We, therefore, sought to assess the relevance of SOX8 to EC progression and patient prognosis. Array comparative genomic hybridization (aCGH) was performed using samples from 50 patients with EC. Samples were separated based upon whether patients were positive for lymph node metastasis (LN+ and LN-, respectively). Based on our initial results, the SOX8 gene was selected for further analysis. Immunohistochemical staining of 630 endometrial tissue samples was conducted to understand how SOX8 expression relates to specific EC clinicopathological characteristics. In addition, we explored the impact of SOX8 expression on the growth, invasion, and migration of EC cells through knockdown and overexpression experiments. In our initial aCGH analysis, SOX family proteins and the Wnt and Notch signaling pathways were significantly associated with EC LN metastasis. SOX8 expression was markedly increased in EC tumor samples relative to normal endometrial tissue (= .003), and higher SOX8 expression was linked to a high tumor histological grade (= .032), LN metastasis (= .027), and shorter patient overall survival (= .031). When SOX8 was knocked down, this further impaired the proliferative, invasive, and migratory activity of EC cells, whereas overexpressing this gene had the opposite effect. SOX8 may function in an oncogenic manner to drive EC development and progression, and higher SOX8 expression is associated with a poor EC patient prognosis.
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http://dx.doi.org/10.1080/15384047.2020.1840318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722791PMC
December 2020

High serum Androgen and Insulin concentrations increase the tendency of Endometrial Carcinoma.

J Cancer 2020 25;11(19):5656-5664. Epub 2020 Jul 25.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

The objective of the study was to evaluate the important role played by androgen and insulin in the development of endometrial carcinoma (EC), and their combined effect on EC risk. We enrolled 510 type I EC patients and 510 age-, time-, and nationality-matched subjects into this study. Metabolic and hormonal parameters of enrolled subjects were examined. Univariate and multivariate logistic regression analyses for EC and control subjects were performed. Type I EC risk was evaluated with respect to testosterone, androstenedione, and insulin levels based on odds ratios (ORs) using stratified data. EC risk was positively associated with C-peptide, estrone, androgen (including testosterone and androstenedione) and insulin levels, BMI, WHR, family history of cancer, nulliparity, irregular menstruation, diabetes, and hypertension. In multivariate logistic regression models, high C-peptide and testosterone levels, diabetes, and hypertension were independent risk factors after adjustment for BMI, WHR, family history of cancer, high serum insulin, and estrone levels. Increased serum total testosterone and insulin levels were positively correlated with EC risk in total, premenopausal, and postmenopausal women. Androstenedione was correlated with EC in total and postmenopausal, but not in premenopausal subjects. Compared with higher testosterone and insulin, odds ratios (ORs) for higher testosterone with lower insulin and lower testosterone with higher insulin were decreased in total, premenopausal, and postmenopausal women. Similarly, compared to both higher FAI and insulin, ORs for higher FAI with lower insulin and lower FAI with higher insulin were decreased in all three groups. Coordinately, ORs for higher androstenedione with lower insulin and lower androstenedione with higher insulin were decreased in total and postmenopausal, but not premenopausal subjects. These findings suggested that androgen and insulin were risk factors of type I EC, and relatively high levels of both testosterone and insulin synergistically affected EC risk.
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http://dx.doi.org/10.7150/jca.46391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477453PMC
July 2020

Ambient PM exposures and systemic biomarkers of lipid peroxidation and total antioxidant capacity in early pregnancy.

Environ Pollut 2020 Nov 4;266(Pt 2):115301. Epub 2020 Aug 4.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, China. Electronic address:

Evidence for effects of PM on systemic oxidative stress in pregnant women is limited, especially in early pregnancy. To estimate the associations between ambient PM exposures and biomarkers of lipid peroxidation and total antioxidant capacity (T-AOC) in women with normal early pregnancy (NEP) and women with clinically recognized early pregnancy loss (CREPL), 206 early pregnant women who had measurements of serum malondialdehyde (MDA) and T-AOC were recruited from a larger case-control study in Tianjin, China from December 2017 to July 2018. Ambient PM concentrations of eight single-day lags exposure time windows before blood collection at the women's residential addresses were estimated using temporally-adjusted land use regression models. Effects of PM exposures on percentage change in the biomarkers were estimated using multivariable linear regression models adjusted for month, temperature, relative humidity, gestational age and other covariates. Unconstrained distributed lag models were used to estimate net cumulative effects. Increased serum MDA and T-AOC were significantly associated with increases in PM at several lag exposure time windows in both groups. The net effects of each interquartile range increase in PM over the preceding 8 days on MDA were significantly higher (p < 0.001) in CREPL [52% (95% CI: 41%, 62%)] than NEP [22% (95% CI: 9%, 36%)] women. Net effects of each interquartile range increase in PM over the preceding 5 days on T-AOC were significantly lower (p = 0.010) in CREPL [14% (95% CI: 9%, 19%)] than NEP [24% (95% CI: 18%, 29%)] women. Exposure to ambient PM may induce systemic lipid peroxidation and antioxidant response in early pregnant women. More severe lipid peroxidation and insufficient antioxidant capacity associated with PM was found in CREPL women than NEP women. Future studies should focus on mechanisms of individual susceptibility and interventions to reduce PM-related oxidative stress in the first trimester.
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http://dx.doi.org/10.1016/j.envpol.2020.115301DOI Listing
November 2020

The effect of pathophysiological changes in the vaginal milieu on the signs and symptoms of genitourinary syndrome of menopause (GSM).

Menopause 2020 08 17;28(1):102-108. Epub 2020 Aug 17.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Importance And Objective: The aim of this study was to provide an overview of the most recent literature on genitourinary syndrome of menopause (GSM), to explore the key elements of GSM diagnosis, and the potential impact of pathophysiological changes in the vaginal milieu on vulvovaginal symptoms.

Methods: The MEDLINE database was searched, and only articles written in English were considered. Additional references were identified by hand searching the bibliographies of the included articles.

Discussions And Conclusion: The vaginal milieu plays important roles in producing bothersome symptoms in the host. In women with GSM, low hormone states can result in pathophysiological changes in the vaginal milieu, including the vaginal microbiome and the mucosal immunity. Hormone-associated disruption of the balance of the indigenous microbiota and the dysregulation of these immune responses are the pathophysiological basis of GSM symptoms. However, whether the microbiome and mucosal immunity are markers of vulvovaginal disorder or agents actively promoting a healthy vagina are still not fully understood. It is an important area of focus.
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http://dx.doi.org/10.1097/GME.0000000000001644DOI Listing
August 2020

Cross‑validation of genes potentially associated with neoadjuvant chemotherapy and platinum‑based chemoresistance in epithelial ovarian carcinoma.

Oncol Rep 2020 Sep 2;44(3):909-926. Epub 2020 Jul 2.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Ovarian carcinomas have the poorest prognosis and the highest mortality among gynecological malignancies. Neoadjuvant chemotherapy (NACT) is considered as a novel therapeutic strategy and an alternative treatment for advanced epithelial ovarian cancer (AEOC). The aim of the present study was to identify the core genes related to platinum‑based NACT resistance in AEOC and to allow screening at the molecular level for the most appropriate ovarian cancer patients for NACT. We obtained three drug‑resistant microarrays GSE114206, GSE41499 and GSE33482 from the Gene Expression Omnibus (GEO) database as well as a microarray representing NACT, GSE109934. Bioinformatics analysis revealed the nature of the four potential candidate genes for using in functional enrichment analyses and interaction network construction. The potential associations and possible genetic alterations among the DEGs were summarized using the STRING database in Cytoscape and the cBioPortal visualization tool, respectively. A total of 63 genes were identified as DEGs from GSE109934 representing NACT. From the drug‑resistant GSE114206 and GSE41499 datasets, 106 DEGs containing 36 upregulated genes and 70 downregulated genes were selected, and from the drug‑resistant GSE114206 and GSE33482 datasets, 406 DEGs with 157 upregulated genes and 249 downregulated genes were selected. The 36 upregulated DEGs and the 70 downregulated genes were notably abundant in the different categories. In KEGG pathway analysis, the 157 upregulated genes and the 249 downregulated genes were concentrated in distinctive signaling pathways. Four potential genes associated with NACT and platinum‑based chemoresistance were screened, including nuclear factor of activated T‑cells, cytoplasmic 1 (NAFTc1), Kruppel‑like factor 4 (KLF4), nuclear receptor subfamily 4 group A member 3 (NR4A3) and hepatocyte growth factor (HGF). Our study showed that the mRNA expression levels of NAFTc1, NR4A3 and HGF were increased in drug‑resistant OC cell lines (all P<0.01), whereas the mRNA expression levels of KLF4 were notably lower in the SKOV3‑CDDP and HeyA8‑CDDP cell line (all P<0.01) but higher in the A2780‑CBP cell line. The NAFTc1, KLF4, NR4A3 and HGF genes may be potential therapeutic targets for NACT and platinum‑based chemoresistance factors as well as candidate biomarkers in AEOC. Determination of the expression levels of these four genes in tumor tissues before planning NACT treatment or initial surgery would be beneficial for AEOC patients.
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http://dx.doi.org/10.3892/or.2020.7668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388274PMC
September 2020

MicroRNA-32 promotes ovarian cancer cell proliferation and motility by targeting SMG1.

Oncol Lett 2020 Jul 14;20(1):733-741. Epub 2020 May 14.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Ovarian cancer (OC) is the most lethal gynecological malignancy and one of the leading causes of cancer-related deaths among women. Metastasis is the main cause of poor prognosis in OC. MicroRNA (miRNA/miR) has been shown to play an important role in tumorigenesis and metastasis in various cancer types by affecting the expression of its targets. In the present study, the role of miR-32 (miR-32-5p) in OC was explored. Reverse transcription-quantitative PCR results showed that miR-32 expression was significantly upregulated in both OC tissues and cell lines. Inhibition of miR-32 by transfection with miR-32 inhibitor in OC cells markedly suppressed cell proliferation, migration and invasion. In addition, a luciferase assay showed that suppressor of morphogenesis in genitalia 1 (SMG1) is a direct target of miR-32, and interference in SMG1 expression with transfection of SMG1 small hairpin RNA restored miR-32-mediated OC cell proliferation, migration and invasion. Taken together, these results indicate that miR-32 may promote OC cell growth and motility by targeting SMG1. The data of the present study suggest that miR-32 may serve as a potential therapeutic target for OC treatment in the future.
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http://dx.doi.org/10.3892/ol.2020.11624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285996PMC
July 2020

Recommendations on management of gynecological malignancies during the COVID-19 pandemic: perspectives from Chinese gynecological oncologists.

J Gynecol Oncol 2020 07 27;31(4):e68. Epub 2020 May 27.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.
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http://dx.doi.org/10.3802/jgo.2020.31.e68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286750PMC
July 2020

miR‑508‑3p suppresses the development of ovarian carcinoma by targeting CCNA2 and MMP7.

Int J Oncol 2020 07 27;57(1):264-276. Epub 2020 Apr 27.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Ovarian cancer is the most lethal gynecological tumor, and the 5‑year survival rate is only ~40%. The poor survival rate is due to cancer diagnosis at an advanced stage, when the tumor has metastasized. A better understanding of the molecular pathogenesis of tumor growth and metastasis is needed to improve patient prognosis. MicroRNAs (miRs) regulate carcinogenesis and development of cancers. However, the role of miR‑508‑3p in ovarian cancer remains largely unknown. Thus, the present study aimed to investigate the possible functions of miR‑508‑3p in the modulation of development of ovarian cancer. The results of the present study demonstrated that miR‑508‑3p mimics inhibited ovarian cancer cell proliferation, migration and invasion. Reporter gene assay results demonstrated that miR‑508‑3p suppressed cancer cell proliferation by directly targeting the 3'‑untranslated region (UTR) of cyclin A2 (CCNA2) and suppressed migration and invasion by directly targeting the 3'‑UTR of matrix metalloproteinase 7 (MMP7). In addition, high CCNA2 and MMP7 expression levels were associated with low miR‑508‑3p expression in ovarian cancer tissues. Furthermore, miR‑508‑3p and CCNA2 were independent predictors for overall survival in patients with ovarian cancer. To the best of our knowledge, this is the first study to demonstrated that miR‑508‑3p suppressed ovarian cancer development by directly targeting CCNA2 and MMP7. The results of this study suggested the potential value of miR‑508‑3p and CCNA2 as prognostic indicators and therapeutics for ovarian cancer.
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http://dx.doi.org/10.3892/ijo.2020.5055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252466PMC
July 2020

ISIDOG Recommendations Concerning COVID-19 and Pregnancy.

Diagnostics (Basel) 2020 Apr 22;10(4). Epub 2020 Apr 22.

Femicare VZW Clinical Research for Women, 3300 Tienen, Belgium.

Providing guidelines to health care workers during a period of rapidly evolving viral pandemic infections is not an easy task, but it is extremely necessary in order to coordinate appropriate action so that all patients will get the best possible care given the circumstances they are in. With these International Society of Infectious Disease in Obstetrics and Gynecology (ISIDOG) guidelines we aim to provide detailed information on how to diagnose and manage pregnant women living in a pandemic of COVID-19. Pregnant women need to be considered as a high-risk population for COVID-19 infection, and if suspected or proven to be infected with the virus, they require special care in order to improve their survival rate and the well-being of their babies. Both protection of healthcare workers in such specific care situations and maximal protection of mother and child are envisioned.
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http://dx.doi.org/10.3390/diagnostics10040243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235990PMC
April 2020

The Proportion and Prognostic Significance of T-Regulatory Cells in Patients with Gynecological Cancers: A Systematic Review and Meta-Analysis.

J Cancer 2020 5;11(11):3340-3348. Epub 2020 Mar 5.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, 154 Anshan Road, He Ping District, Tianjin 300052, China.

: Multiple reports have described the proportion of T-regulatory cells (Tregs) in peripheral blood (PB) and tissues in patients with gynecological cancers (GCs) with controversial results. Thus, the aim of this study was to investigate the proportion of Tregs and its prognostic survival role in GCs patients. : We performed a comprehensive search from database inception for all studies presenting changes of Tregs in GCs patients versus controls to evaluate the pooled standardized mean differences (SMD) with 95% confidence intervals (95% CI). And hazard ratios (HRs) with 95% CI were recorded if available to determine the prognostic significance of Tregs. : Totally, 22 studies were included. Compared with controls, GCs patients had a higher proportion of Tregs in PB (SMD = 2.32, 95% CI = 1.47 to 3.17, = 0.000) as well as in tissues (SMD = 3.47, 95% CI = 0.77 to 6.18, = 0.012). Furthermore, more significant elevated frequency of Tregs was observed in GCs patients with advanced stage than those in the early stage in both PB and tissues. However, no association was found between Tregs and survival of GCs patients with an HR of 1.34 (95% CI = 0.96 to 1.88, = 0.09). : Compared to controls, proportion of Tregs in PB and tissues was both higher among GCs patients, and it can be considered as a clinical biomarker for screening and prediction of clinical characteristics of GCs patients. But larger researches with rigorous design should be carried to explore the deep mechanisms of Tregs in GCs.
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http://dx.doi.org/10.7150/jca.42472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097934PMC
March 2020

Vaginal bacterial profiles of aerobic vaginitis: a case-control study.

Diagn Microbiol Infect Dis 2020 Apr 7;96(4):114981. Epub 2020 Jan 7.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

Purpose: Aerobic vaginitis (AV) has drawn increasing attention because of its threat to women's reproductive health and pregnancy. However, little is known about the overall structure of vaginal bacterial communities in women with AV.

Methods: The diversity of vaginal microbiota was evaluated by amplicon sequencing targeting the 16S rRNA V4 region. Routine laboratory tests, including cultivation, were used.

Results: Firmicutes (mainly Lactobacillus crispatus and L. iners) were dominant in healthy women (n = 160), while Actinobacteria and Bacteroidetes were strongly associated with AV (n = 80). The onset of AV was marked by a striking decline in L. crispatus and an increase in multiple aerobes, including Streptococcus agalactiae, S. anginosus, etc. The overall drug resistance level of gram-positive bacteria against erythromycin and clindamycin was high, and the overall drug resistance level of gram-negative bacteria against ampicillin was high.

Conclusions: Multiple aerobes and facultative anaerobes were involved in vaginal dysbiosis, which was associated with decreasing L. crispatus levels. Probiotics containing L. crispatus may be potential supplementary agents.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.114981DOI Listing
April 2020

Incarceration of the gravid uterus: a case report and literature review.

BMC Pregnancy Childbirth 2019 Nov 8;19(1):408. Epub 2019 Nov 8.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, People's Republic of China, 300052.

Background: Incarceration of the gravid uterus is a rare obstetric disorder that contributes to pregnancy-related complications. To understand its clinical characteristics and managements, we have reviewed the etiology, risk factors, clinical characteristics and current treatments of an incarcerated gravid uterus based on 162 cases reported in the English language literature, including our patient.

Case Presentation: A 25-year-old primigravida, with a history of lymphatic tuberculosis, infertility due to blocked fallopian tubes and received in vitro fertilization. The patient presented with urine retention and lower abdominal pain in the early second trimester. Uterine incarceration was diagnosed based on pelvic examination and abdominal ultrasound. A Foley catheter was placed and manual reposition was successful. No episode of retention was experienced after the further enlargement of the uterus and its ascent. A healthy infant was delivered vaginally on 38th week of pregnancy.

Conclusions: Uterine incarceration due to pelvic adhesions is rare and, because of it non-specific clinical presentations, is often misdiagnosed. Abdominal ultrasound is instrumental for the diagnosis because it can directly image the disturbed uterine and pelvic anatomy. There are limited treatment options for uterine incarceration, but definitive diagnosis allows procedures to treat and to reduce severe complications of uterine incarceration.
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http://dx.doi.org/10.1186/s12884-019-2549-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839127PMC
November 2019

Syncytiotrophoblast-Derived Extracellular Vesicles in Pathophysiology of Preeclampsia.

Front Physiol 2019 1;10:1236. Epub 2019 Oct 1.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.

Preeclampsia is a common obstetric complication associated with pregnancy and it endangers lives of the mother and the infant. The histopathological changes associated with preeclampsia include systemic endothelial dysfunction, persistent inflammatory state, and coagulation and fibrinolysis dysregulations. Preeclampsia is considered to be caused by the systemic vasoconstriction of small arteries and disruption of the endothelial integrity, resulting in hypertension, proteinuria, and multiple organ dysfunction. However, mediators that trigger or propagate the pathology of preeclampsia remain poorly defined. Syncytiotrophoblast-derived extracellular vesicles (SDEVs) are increasingly recognized as a key mediator for the development of preeclampsia, but the underlying mechanisms through which these SDEVs are released and induce systemic responses are not fully understood. This review focuses on multiple roles of SDEVs in the pathogenesis of preeclampsia.
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http://dx.doi.org/10.3389/fphys.2019.01236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779799PMC
October 2019

genes: regulators and biomarkers in gynecological cancers.

Cancer Biol Med 2019 Aug;16(3):462-474

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.

genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis. genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical, and endometrial cancer. In this review, we summarize the contrasting regulatory roles of genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels. Expression levels of genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers. An understanding of the mechanisms whereby genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of expression levels will help to predict the prognosis of patients with gynecological cancers.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743626PMC
August 2019

Identification of key genes and pathways between type I and type II endometrial cancer using bioinformatics analysis.

Oncol Lett 2019 Sep 28;18(3):2464-2476. Epub 2019 Jun 28.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Endometrial carcinoma (EC) is a common malignant neoplasm of the female reproductive tract. The malignant degree of type II EC is much greater than that of type I EC, usually presenting with a high recurrence rate and a poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in type I and type II EC and reveal their potential mechanisms. Differentially expressed genes (DEGs) were selected from the gene expression profiles derived from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In the present study, the KEGG pathway enrichment analysis revealed that 5,962 upregulated DEGs were significantly enriched in the 'p53 signaling pathway' and involved in 'lysine degradation'. In addition, 3,709 downregulated DEGs were enriched in 'pathways in cancer', as well as 'tight junction regulation', the 'cell cycle' and the 'Wnt signaling pathway'. The 13 top hub genes MAPK1, PHLPP1, ESR1, MDM2, CDKN2A, CDKN1A, AURKA, BCL2L1, POLQ, PIK3R3, RHOQ, EIF4E and LATS2 were identified via the protein-protein interaction network. Furthermore, the OncoPrint algorithm from cBioPortal declared that 25% of EC cases carried genetic alterations. The altered DEGs (MAPK1, MDM2, AURKA, EIF4E and LATS2) may be involved in tumor differentiation and may be valuable diagnostic biomarkers. In conclusion, a number of principal genes were identified in the present study that may be determinants of poorly differentiated type II EC carcinogenesis, which may contribute to future research into potential molecular mechanisms. In addition, these genes may help identify candidate biomarkers and novel therapeutic targets for type II EC.
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http://dx.doi.org/10.3892/ol.2019.10550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676660PMC
September 2019

High level of visfatin and the activation of Akt and ERK1/2 signaling pathways are associated with endometrium malignant transformation in polycystic ovary syndrome.

Gynecol Endocrinol 2020 Feb 27;36(2):156-161. Epub 2019 Aug 27.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

This study aimed to assess the clinicopathological significance of serum levels and endometrium tissue expression of visfatin in polycystic ovary syndrome (PCOS) patients. A total of 80 PCOS patients and 80 matching controls were included in this study. We analyzed the relationship between the expression of visfatin in endometrium and clinicopathological characteristics in PCOS patients. The correlation between the expression of visfatin and p-Akt, Akt, p-ERK1/2, and ERK1/2 in PCOS tissues was evaluated as well. Visfatin expression in PCOS endometrial tissues were significantly higher than those in controls ( = .001). The expression of phosphorylation of Akt and ERK1/2 were significantly higher in PCOS endometrium tissues compared to controls ( < .05). Moreover, a high expression of tissue visfatin in PCOS tissues was positively correlated with the expression of p-Akt ( = .015), and p-ERK1/2 ( = .013). Western blotting revealed that protein expression of visfatin in PCOS patients with endometrial hyperplasia and cancer was higher than that in patients with normal endometrium tissues, and the difference was statistically significant ( = .027). The expression of p-Akt ( = .018) and p-ERK1/2 ( = .035) in PCOS patients with endometrial hyperplasia and cancer was significantly higher than that in patients with normal endometrium tissues. Visfatin may be a potential biomarker for endometrial malignant transformation in PCOS patients.
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http://dx.doi.org/10.1080/09513590.2019.1650340DOI Listing
February 2020

Placenta-derived extracellular vesicles induce preeclampsia in mouse models.

Haematologica 2020 06 22;105(6):1686-1694. Epub 2019 Aug 22.

Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China

Preeclampsia is a pregnancy-induced condition that impairs the mother's health and results in pregnancy termination or premature delivery. Elevated levels of placenta-derived extracellular vesicles (pcEV) in the circulation have been consistently associated with preeclampsia, but whether these vesicles induce preeclampsia or are the product of preeclampsia is not known. Guided by a small cohort study of preeclamptic patients, we examined the impact of pcEV on the pathogenesis of preeclampsia in mouse models. We detected pcEV in pregnant C56BL/6J mice with a peak level of 3.8±0.9×10/mL at 17-18 days post-coitum. However, these pregnant mice developed hypertension and proteinuria only after being infused with vesicles purified from injured placenta. These extracellular vesicles released from injured placenta disrupted endothelial integrity and induced vasoconstriction. Enhancing the clearance of extracellular vesicles prevented the development of the extracellular vesicle-induced preeclampsia in mice. Our results demonstrate a causal role of pcEV in preeclampsia and identify microvesicle clearance as a new therapeutic strategy for the treatment of this pregnancy-associated complication.
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http://dx.doi.org/10.3324/haematol.2019.226209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271597PMC
June 2020

Diagnostic accuracy of preoperative F-FDG PET or PET/CT in detecting pelvic and para-aortic lymph node metastasis in patients with endometrial cancer: a systematic review and meta-analysis.

Arch Gynecol Obstet 2019 09 4;300(3):519-529. Epub 2019 Jun 4.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, 154 Anshan Road, He Ping District, Tianjin, 300052, China.

Purpose: The aim of this study was to assess the diagnostic accuracy of preoperative F-FDG PET or PET/CT in detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastasis in patients with endometrial cancer (EC) in systematic review and meta-analysis format.

Methods: A comprehensive search was performed on PubMed, Cochrane Library, EMBASE, Web of science, SpringerLink and Science Direct for studies reporting the diagnostic value of preoperative F-FDG PET or PET/CT in detecting PLN and PALN metastasis had been published up to August 8, 2018. Studies were included if enough data could be extracted for calculation of diagnostic accuracy indices.

Results: Nineteen studies (1431 patients in total) were included in the analysis. On a lymph node basis, the overall pooled sensitivity, specificity, AUC and overall diagnostic accuracy (Q* index) of F-FDG PET or PET/CT in detecting total lymph node metastasis were 0.68 (95% CI 0.63-0.73), 0.96 (95% CI 0.96-0.97), 0.82, and 0.75, respectively. The corresponding indices for detecting PLN metastasis were 0.61 (95% CI 0.52-0.69), 0.96 (95% CI 0.95-0.97), 0.79, and 0.73, respectively. And the corresponding value for detection of PALN were 0.70 (95% CI 0.58-0.79), 0.92 (95% CI 0.9-0.94), 0.84, and 0.77, respectively. Data based on patients also performed well.

Conclusions: F-FDG PET and PET/CT both have excellent diagnostic performance for detecting lymph node metastasis, including PLN and PALN metastasis, in patients with endometrial cancer preoperatively. Though the utility of this method is limited due to its moderate sensitivity, it can help surgeons make better-tailored surgical decision for its high specificity.
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http://dx.doi.org/10.1007/s00404-019-05207-8DOI Listing
September 2019

Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways.

Cancer Biol Med 2019 Feb;16(1):55-70

Department of Gynecology and Obstetrics.

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 and , 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.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528450PMC
February 2019

Reply to comments on "Risk factors, microbiology and management of infected lymphocyst after lymphadenectomy for gynecologic malignancies".

Arch Gynecol Obstet 2019 06 6;299(6):1749-1750. Epub 2019 Apr 6.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, 154# AnShan Road, Heping District, Tianjin, 300052, People's Republic of China.

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http://dx.doi.org/10.1007/s00404-019-05055-6DOI Listing
June 2019

Upregulation of lncRNA AB073614 functions as a predictor of epithelial ovarian cancer prognosis and promotes tumor growth in vitro and in vivo.

Cancer Biomark 2019 ;24(4):421-428

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.

Backgrounds: Upregulation of lncRNA AB073614 is found in some cancer types and involved in tumor development and progression including ovarian cancer. However, the clinical value and functional role of lncRNA AB073614 in epithelial ovarian cancer (EOC) still needed to be investigated.

Methods: We examined lncRNA AB073614 expression using quantitative real time polymerase chain reaction (qRT-PCR) in 75 paired of EOC tissue samples and adjacent normal tissues. Association of lncRNA AB073614 expression with overall survival (OS) was evaluated using Kaplan-Meier analysis. Univariate and multivariate analysis of factors associated with OS were assessed in EOC patients. After lncRNA AB073614 knockdown using siRNAs, the cell viability and cell colony forming assays were performed. Western blot analysis was used to assess relative protein expression.

Results: In present study, we demonstrated that lncRNA AB073614 was significantly upregulated in ovarian cancer tissues compared to adjacent normal tissues in patients. Higher lncRNA AB073614 expression significantly associated with tumor size, lymph node invasion, FIGO stage, and shorter OS rate of EOC patients. Furthermore, multivariate Cox regression analysis results showed that higher lncRNA AB0736141 was identified as an independent risk factor of OS in EOC patients. Moreover, we demonstrated that lncRNA AB0736141 knockdown suppressed EOC cell proliferation ability and cell colony formation in vitro. In vivo, we showed that AB0736141 knockdown suppressed tumor growth. We also revealed that lncRNA AB0736141 knockdown inhibited the PTEN/PI3K/AKT signaling pathway in EOC.

Conclusions: Thus, these results indicated that LncRNA AB073614 may serve as a prognostic biomarker and potential target of treatment for EOC.
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http://dx.doi.org/10.3233/CBM-182160DOI Listing
August 2019
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