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Cancer-associated fibroblasts (CAFs) are crucial co-mediators of breast cancer progression. Estrogen is the predominant driving force in the cyclic regulation of the mammary extracellular matrix, thus potentially affecting the tumor-associated stroma. Recently, a third estrogen receptor, estrogen (G-protein-coupled) receptor (GPER), has been reported to be expressed in breast CAFs. In this study, GPER was detected by immunohistochemical analysis in stromal fibroblasts of 41.8% (59/141) of the primary breast cancer samples. GPER expression in CAFs isolated from primary breast cancer tissues was confirmed by immunostaining and RT-PCR analyses. Tamoxifen (TAM) in addition to 17β-estradiol (E2) and the GPER agonist G1 activated GPER, resulting in transient increases in cell index, intracellular calcium, and ERK1/2 phosphorylation. Furthermore, TAM, E2, and G1 promoted CAF proliferation and cell-cycle progression, both of which were blocked by GPER interference, the selective GPER antagonist G15, the epidermal growth factor receptor (EGFR) inhibitor AG1478, and the ERK1/2 inhibitor U0126. Importantly, TAM as well as G1 increased E2 production in breast CAFs via GPER/EGFR/ERK signaling when the substrate of E2, testosterone, was added to the medium. GPER-induced aromatase upregulation was probably responsible for this phenomenon, as TAM- and G1-induced CYP19A1 gene expression was reduced by GPER knockdown and G15, AG1478, and U0126 administration. Accordingly, GPER-mediated CAF-dependent estrogenic effects on the tumor-associated stroma are conceivable, and CAF is likely to contribute to breast cancer progression, especially TAM resistance, via a positive feedback loop involving GPER/EGFR/ERK signaling and E2 production.

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.Jie Tang, MD, Ph.D, Professor 283 Tongzipo Road, Yuelu District,

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Objectives To evaluate the association between serum iron levels and cervical cancer risk in Chinese populations. Methods A literature search was conducted using the PubMed, WanFang, and SinoMed databases up to April 30, 2019. Pooled standard mean differences (SMD) and 95% confidence intervals (CI) were analyzed using R software with a random-effects model. Results Data from nine studies comprising 454 cervical cancer patients and 880 controls were used in the analysis. Our results demonstrated that serum iron levels in cervical cancer patients were significantly lower than those in controls in Chinese populations (summary SMD = −1.24, 95%CI = −1.37 to −1.10; I2 = 93.4%). No publications bias was detected. Sensitivity analysis indicated that no single study had a significant effect on the overall SMD. Conclusions Our findings show that serum iron levels are lower in patients with cervical cancer than in control individuals. However, further high-quality studies are necessary to clarify the role of serum iron levels in cervical cancer risk.

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Background velamentous cord insertion (VCI) and marginal cord insertion (MCI) are well-known risk factors for adverse perinatal outcomes in singleton pregnancies. However, the potential links between VCI or MCI and perinatal outcomes in twin pregnancies have yet to be systematically evaluated. This study aimed to investigate the relationships between VCI or MCI and perinatal outcomes, neonatal outcomes in twin pregnancies. Methods This was a retrospective single-center cohort study that included women with twin pregnancies and gave birth in a tertiary hospital in Southwest, China between January 2017 and December 2022. VCI and MCI were identified by abdominal ultrasound and checked after placenta delivery. Logistic regression models, multinomial logit regression models and generalized estimation equation models were used to evaluated the association between VCI or MCI and perinatal outcomes. Results 3682 twin pregnancies were included, 100 (2.7%) pregnancies with VCI and 149 (4.0%) pregnancies with MCI. Compared to pregnancies with normal cord insertion, pregnancies with VCI were associated with an increased risk of preterm delivery 32–34 weeks both in monochorionic twins (aRRR 2.94, 95% CI 1.03–8.39) and dichorionic twins (aRRR 2.55, 95% CI 1.19–5.46), while pregnancies with MCI were not associated with preterm delivery. Pregnancies with VCI were associated with higher incidence of placental previa (aOR 6.36, 95% CI 1.92–21.04) in monochorionic twins and placental accreta in dichorionic twins (aOR 1.85, 95% CI 1.06–3.23). Pregnancies with MCI were associated with increased risk of preeclampsia (aOR 3.07, 95% CI 1.49–6.32), intertwin birthweight discordance ≥ 20% (aOR 2.40, 95% CI 1.08–5.60) and selective fetal growth restriction (aOR 2.46, 95% CI 1.08–5.60) in monochorionic twins and small-for-gestational age neonates (aOR 1.97, 95% CI 1.24–3.14) in dichorionic twins. Conclusions Twin pregnancies with VCI were associated with an increased risk of preterm delivery irrespective of chorionicity, whereas twin pregnancies with MCI were associated with an increased risk of preeclampsia, significant intertwin birthweight discordance in monochorionic twins and small-for-gestational age neonates in dichorionic twins.