Artesunate-induced ATG5-related autophagy enhances the cytotoxicity of NK92 cells on endometrial cancer cells via interactions between CD155 and CD226/TIGIT.

Uterine corpus endometrial carcinoma (UCEC) is the most prevalent gynecologic cancer in developed countries and lacks efficient therapeutic strategies. Artesunate (ART), a well-modified derivate of artemisinin, exerts potent anti-cancer effects apart from its classical anti-malaria feature. Autophagy is a universal double-edged process in cell survival, and CD155 is a novel immune checkpoint highly expressed in numerous cancers.

Preoperative CD4CD25/CD4 and tumor diameter predict prognosis in male patients with bladder cancer.

The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4CD25/CD4 and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test.

Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism.

Background: Excessive estrogen exposure is an important pathogenic factor in uterine endometrial cancer (UEC). Recent studies have reported the metabolic properties can influence the progression of UEC. However, the underlying mechanisms have not been fully elucidated.

Decidual stromal cells promote the differentiation of CD56 CD16 NK cells by secreting IL-24 in early pregnancy.

Problem: Decidual stromal cells (DSCs) are important origins of cytokines to modulate maternal-fetal immunotolerance and provide a feasible environment for embryo implantation and development. Interleukin (IL)-24 is a multifunctional cancer killing cytokine and a pleiotropic immunoregulator with complex potency according to tissue or cell types. Its role in establishment and maintenance of normal pregnancy is largely unknown.

Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF-1α/ROS/VEGF.

Angiogenesis is an essential process involved in various physiological, including placentation, and pathological, including cancer and endometriosis, processes. Melatonin (MLT), a well‑known natural hormone secreted primarily in the pineal gland, is involved in regulating neoangiogenesis and inhibiting the development of a variety of cancer types, including lung and breast cancer. However, the specific mechanism of its anti‑angiogenesis activity has not been systematically elucidated.

High Glucose Promotes Epithelial-Mesenchymal Transition of Uterus Endometrial Cancer Cells by Increasing ER/GLUT4-Mediated VEGF Secretion.

Background/aims: Uterus endometrial cancer (UEC) is the common malignancy among gynecologic cancers, and most of them are type I estrogen-dependent UEC. Diabetes is well-known risk factor for the development of UEC. However, the underlying link between high glucose (HG) and the estrogen receptor in UEC remains unclear.

miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10.

MicroRNA (miR)‑26a‑5p and miR‑26b‑5p consistently play an antitumor role in many types of cancers, but the underlying mechanism remains unclear in bladder cancer (BC). In the present study, we found that, in BC tissues, the levels of miR‑26a‑5p and miR‑26b‑5p were lower than in paired normal tissues. The upregulation of miR‑26‑5p significantly inhibited the proliferation of BC cell lines (T24 and 5637).

Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: A novel chemoimmunomodulating strategy.

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention.

The role of the SDF-1/ CXCR7 axis on the growth and invasion ability of endometrial cancer cells.

Purpose: Stroma-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) are involved in human endometrial carcinoma (EC) progression. CXCR7 is another important receptor of SDF-1 and has a higher affinity with SDF-1 compared with that of CXCR4. This paper aims to study the effects of the SDF-1/CXCR7 axis on the growth and invasion ability of EC cells.

Mutant p53 induces EZH2 expression and promotes epithelial-mesenchymal transition by disrupting p68-Drosha complex assembly and attenuating miR-26a processing.

The tumor suppressor p53 and the transcriptional repressor Enhancer of Zeste Homolog 2 (EZH2) have both been implicated in the regulation of epithelial-mesenchymal transition (EMT) and tumor metastasis via their impacts on microRNA expression. Here, we report that mutant p53 (mutp53) promotes EMT in endometrial carcinoma (EC) by disrupting p68-Drosha complex assembly. Overexpression of mutp53 has the opposite effect of wild-type p53 (WTp53), repressing miR-26a expression by reducing pri-miR-26a-1 processing in p53-null EC cells.

Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK-NF-κB signaling pathway.

Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis.

Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17β-estradiol biosynthesis in endometrial carcinoma microenvironment.

Tumor-stroma interactions contribute greatly to intratumoral estrogen biosynthesis in endometrial carcinoma, but the mechanisms involved remain largely unknown. Previous study demonstrated that intratumoral aromatase upregulation in stromal cells participated in this process, but the specific aromatase-regulators have not been reported. In the present study, we found that aromatase expression in intratumoral stroma, but not in tumor epithelium, correlated positively with interleukin 6 (IL-6) expression in cancer epithelial cells by immunohistochemistry, which was confirmed using laser capture microdissection/real-time reverse transcription-PCR.

The decidual stromal cells-secreted CCL2 induces and maintains decidual leukocytes into Th2 bias in human early pregnancy.

The precise mechanism of characteristic Th2 predominance at maternal-fetal interface remains unresolved. In the present study, we investigated roles of the decidua-derived CCL2 in Th2 predominance at maternal-fetal interface. FCM shows that 55% CD56(+)CD16(-)CD3(-) decidual NK, 52% CD4(+) T cells and 75% CD14(+) monocytes express CCR2.

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells.

The selective ER modulator tamoxifen (TAM(1)) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer.

Estrogenic transmembrane receptor of GPR30 mediates invasion and carcinogenesis by endometrial cancer cell line RL95-2.

Purpose: The mechanisms underlying the effects of estrogen on endometrial cancer remain undefined. Although the classical mechanism of the action of estrogen involves binding to the estrogen receptors α and β, and transduction of the signal into the cell, G protein-coupled receptor (GPR) 30 has been shown to mediate nongenomic estrogen signaling. The goal of this study was to determine the role of GPR30 signal in the basic process such as invasion and carcinogenesis of endometrial cancer.

Crosstalk between estrogen receptor and mitogen-activated protein kinase signaling in the development and progression of endometrial cancer.

Objective: The objectives of the study were to evaluate the role of mitogen-activated protein kinase (MAPK) signaling in normal, hyperplastic, and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether 17β-estradiol (E2) and tamoxifen (TAM) mediate the proliferation and apoptosis of endometrial cancer cells through the MAPK pathway.

Methods: The expressions of phosphorylated and total extracellular signal-regulated kinases 1/2 (phosphorylated extracellular signal-regulated kinase 1/2 [p-ERK1/2] and total ERK1/2 [t-ERK1/2]) were analyzed with immunohistochemistry in normal, hyperplastic, and neoplastic endometrium. The expression levels of p-ERK1/2 and t-ERK1/2 in RL95-2 and KLE after stimulation by E2, progesterone (P), and TAM were detected by Western blotting.

Aberrant methylation of breast and ovarian cancer susceptibility gene 1 in chemosensitive human ovarian cancer cells does not involve the phosphatidylinositol 3'-kinase-Akt pathway.

Methylation is an important silencing mechanism of breast and ovarian cancer susceptibility gene 1 (BRCA1) expression in sporadic ovarian cancer. However, the role of BRCA1 methylation in chemotherapy in sporadic ovarian cancer and the related pathways have not been understood completely. This study has determined the roles of BRCA1 hypermethylation in chemotherapy of sporadic ovarian cancer and its related signaling pathways.

Kallikrein 4 overexpression in endometrial carcinoma and upregulation by estrogen via mitogen-activated protein kinase signal pathway.

Objective: The aim of this study was to investigate the expression of kallikrein 4 (KLK4) and the potential signal pathway through which estrogen up-regulates KLK4 in endometrial cancer.

Methods: The expression of KLK4 was analyzed in 15 human normal endometrium, 13 hyperplasia endometrium, and 68 endometrioid adenocarcinoma by immunohistochemistry. After exposure to 17beta-estradiol and/or to the mitogen-activated protein kinase (MAPK) inhibitor U0126 and to the PI3K inhibitor LY294002, the expression of KLK4 in the endometrial cancer cell lines KLE and RL95-2 was detected with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot.

Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway.

The regulatory mechanism of endometrial carcinoma and the signal transduction pathways involved in hormone action are poorly defined. It has become apparent that the G protein-coupled receptor (GPR) 30 mediates the non-genomic signaling of 17beta-estradiol (E2). Here we show that GPR30 is highly expressed in endometrial cancer tissues and cancer cell lines and positively regulates cell proliferation and invasion.

[Anoikis-suppression and invasion induced by tyrosine kinase receptor B in OVCAR3 ovarian cancer cells].

Objective: To study the relationship between tyrosine kinase receptor B (TrkB) expression and anoikis-suppression and invasion in OVCAR3 ovarian cancer cells.

Methods: The expression of TrkB mRNA in OVCAR3 ovarian cancer cells under two culture conditions: adhesive cells and cell-spheroids were evaluated by RT-PCR and real-time PCR. The relationship between TrkB expression and anoikis-suppression of OVCAR3 ovarian cancer cells was examined by RNA interference (RNAi) technic, anchorage independent culture and fluorescence-activated cell sorting analysis.

Combination of estrogen and dioxin is involved in the pathogenesis of endometriosis by promoting chemokine secretion and invasion of endometrial stromal cells.

Background: The CC chemokines, regulated on activation, normal T-cell expressed and secreted (RANTES) and macrophage-inflammatory protein-1alpha (MIP-1alpha), have been identified as potential contributors to the pathogenesis and the progression of endometriosis. Dioxin, an air pollutant, and estrogen also appear to be involved in endometriosis. The aim of this study was to probe into the effect of dioxin and estrogen on expression of the chemokines in endometriosis-associated cells, and to explore the pathogenesis of endometriosis.

Cyclosporin A promotes growth and invasiveness in vitro of human first-trimester trophoblast cells via MAPK3/MAPK1-mediated AP1 and Ca2+/calcineurin/NFAT signaling pathways.

Cyclosporin A (CsA) has provided the pharmacologic foundation for organ transplantation as a calcineurin inhibitor blocking T-cell activation. We have demonstrated that CsA promoted trophoblast viability/proliferation and invasion in vitro. In the present study, we further investigated the intracellular signalling pathways involved in enhancing cell viability/proliferation and invasiveness of the human trophoblast induced by CsA.

Regulation of C-C motif chemokine ligand 2 and its receptor in human decidual stromal cells by pregnancy-associated hormones in early gestation.

Background: Decidua is in close contact with the fetal trophoblasts, and involved in immune relationship of mother to fetus. However, the roles of decidua and decidual stromal cells (DSC) in materno-fetal immune regulation remain to be elucidated. In the present study, the expression and regulation of chemokines and their receptors in decidua and DSCs were investigated.

Cyclosporine A induces titin expression via MAPK/ERK signalling and improves proliferative and invasive potential of human trophoblast cells.

Background: Cyclosporin A (CsA) is a powerful immunosuppressive that has been widely used to prevent organ rejection and to treat certain autoimmune diseases. Our previous study showed that CsA at low concentrations could promote proliferation and invasion, and inhibit apoptosis, of human first trimester trophoblasts. In the present study, we further explored the potential mechanism and signal pathway.

[Modulation of cyclosporin a on the expression of MMP-9 AND MMP-2 of the first-trimester human trophoblast cells].

The aim of this study was to explore whether cyclosporine A (CsA) can modulate expression of MMP-9 and MMP-2 and invasion of the first-trimester human trophoblast cells. The invasive ability of the trophoblast cells modulated by CsA was observed by Matrigel invasion assay. The effect of CsA on the transcription and translation of MMP-9 and MMP-2 was determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Gelatin Zymography.