The MRI estimations of placental volume, T2 dark band volume, and cervical length correlate with massive hemorrhage in patients with placenta accreta spectrum disorders.

PURPOSE: To identify whether placental volume, T2 dark band volume, and cervical length measured by MRI correlate with massive hemorrhage (MH) in patients with placenta accreta spectrum (PAS) disorders. METHODS: A total of 163 pregnant women with PAS underwent preoperative MRI examination were divided into MH group and non-MH group. The placental volume, T2 dark band volume, and cervical length of PAS patients were measured and evaluated their ability to identify MH in patients with PAS. RESULTS: Patients with MH had a significantly larger placental volume, larger T2 dark band volume, and shorter cervical length than patients without MH (all P < 0.001). Multivariable logistic regression showed that placental volume (> 890 cm3), T2 dark band volume (> 35 cm3), and cervical length (< 30 mm) were significant independent risk factor in identification of MH. In all PAS patients, a positive linear correlation was found between placental volume and amount of blood loss (r = 0.527), and between T2 dark band volume and amount of blood loss (r = 0.642), and a negative linear correlation was found between cervical length and amount of blood loss (r = - 0.597). When combined with the three MRI indicators, the sensitivity and specificity in identifying cases at high risk for MH were 91.638% and 94.051%, respectively, with area under the curve (AUC) of 0.923. CONCLUSION: The placental volume, T2 dark band volume, and cervical length might be used to predict MH in patients with PAS.

Placental volume as a novel sign for identifying placenta accreta spectrum in pregnancies with complete placenta previa.

BACKGROUND: Placenta accreta spectrum (PAS) carries an increased risk of maternal-fetal mortality and morbidity, and magnetic resonance imaging (MRI) features for PAS have been used for preoperative identification. This study aims to investigate the role of placental volume evaluated by MRI in identifying PAS in pregnant women with complete placenta previa. METHODS: Totally 163 cases of complete placenta previa pregnant women with a history of cesarean section underwent MRI for suspected PAS were included. We categorized the patients into two groups according to the presence or absence of PAS, and the maternal-fetal perinatal outcomes and placental volume analyzed by 3D Slice software were compared. RESULTS: There were significantly more gravidity, parity, and number of previous cesarean delivery in the PAS group (P < 0.05). Significant differences were also found between the two groups with respect to the following baseline characteristics: gestational age at delivery, intraoperative blood loss, blood transfusion, and neonatal birth weight (P < 0.05). Of 163 women in the study, 7 (4.294%) required cesarean hysterectomy for high-grade PAS or pernicious bleeding during cesarean section, and PAS was confirmed with histologic confirmation in 6 (85.714%) cases. The placental volume in PAS group was greater than that in the non-PAS group (P < 0.05). With a threshold of more than 887 cm3, the sensitivity and specificity in identifying PAS were 85.531% and 83.907% respectively, with AUC 0.908 (95% CI: 0.853-0.948). CONCLUSIONS: Placental volume may be a promising indicator of PAS in complete placenta previa patients with a history of cesarean section.

Intrahepatic Cholestasis of Pregnancy Is Associated with Reduced Nitric Oxide Synthase (iNOS) in Plasma and Placentas: A Pilot Study.

BACKGROUND Intrahepatic cholestasis of pregnancy (ICP) is a condition specific to pregnancy, leading to increased fetal morbidity and mortality. Nitric oxide synthase (iNOS) may be a factor regulating the vasodilation of blood vessels, which are relevant to ischemic-hypoxic conditions. We aimed to explore the potential relationship between iNOS and ICP. MATERIAL AND METHODS A prospective, case-control study was conducted including 77 pregnant women with ICP and 80 healthy pregnant women as controls. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS levels. The placenta mRNA levels and cell-specific localization of iNOS were determined by quantitative polymerase chain reaction, western blotting, and immunohistochemical analysis. A multivariate linear regression model was used to identify the independent factors of serum total biliary acids (TAB) in ICP. RESULTS Compared with controls, the expression of iNOS was significantly lower in maternal serum and placentas with ICP (P<0.001). Maternal plasm iNOS levels were negatively correlated with TAB (r=-0.450, P<0.001), cholyglycine (r=-0.367, P<0.001), alanine aminotransferase (r=-.359, P<0.001), and aspartate aminotransferase (r=-0.329, P<0.001). iNOS level was an indicator for ICP by multivariate linear regression analysis (ß=-0.505, P<0.001). The ROC curve indicated the optimal cut-off level for iNOS was 2865.43 pg/mL (sensitivity, 85.71%; specificity, 63.75%). The ROC curve area for iNOS was 0.793 (95% CI 0.722-0.864). CONCLUSIONS iNOS plays an important role in poor fetoplacental vascular perfusion and adverse pregnancy outcomes. iNOS can provide complementary information in predicting the extent and severity of ICP.

LINC00319 promotes migration, invasion and epithelial-mesenchymal transition process in cervical cancer by regulating miR-3127-5p/RPP25 axis.

Cervical cancer is among the most prevalent malignancies for women. An increasing number of evidences have been proved that long non-coding RNAs (lncRNAs) play significant role in the initiation and progression of cervical cancer. However, the function of long intergenic non-protein coding RNA 319 (LINC00319) in cervical cancer still remains vague. In this study, our purpose was to investigate the effects of LINC00319 on cell migration, invasion and epithelial-mesenchymal transition (EMT) process in cervical cancer. It confirmed that LINC00319 was highly expressed in tissues and cell lines in cervical cancer. Further, overexpression of LINC00319 accelerates cell migration, invasion and EMT in cervical cancer. Moreover, LINC00319 could bind with miR-3127-5p and negatively regulated its expression. Besides, RPP25 was targeted by miR-3127-5p, and its expression was negatively/positively regulated by miR-3127-5p/LINC00319. Additionally, miR-3127-5p mimics or RPP25 insufficiency could offset the encouraging effects of LINC00319 overexpression on migration, invasion and EMT process in cervical cancer. Generally speaking, LINC00319 promotes migration, invasion and EMT process in cervical cancer by regulating miR-3127-5p/RPP25 axis, which may be conductive to cervical cancer treatment.

TMPO-AS1 promotes cervical cancer progression by upregulating RAB14 via sponging miR-577.

BACKGROUND: Accumulating evidence has shown that long non-coding RNAs play a key role in cancer initiation and development. However, the effect of TMPO antisense RNA 1 (TMPO-AS1) on the progression of cervical cancer (CC) remains to be determined. METHODS: The mRNA expression of TMPO-AS1, miR-577 and RAB14 was measured by a quantitative reverse transcriptase-polymerase chain reaction. The protein level of RAB14 was detected by western blotting. The function of TMPO-AS1 in CC was measured via Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine and transwell assays, as well as by flow cytometry analysis. Nuclear-cytoplasmic fractionation and RNA-fluorescence in situ hybridization validated the subcellular position of TMPO-AS1. An interaction between miR-577 and TMPO-AS1 or RAB14 was confirmed by luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. RESULTS: TMPO-AS1 was highly expressed in CC. In addition, TMPO-AS1 knockdown inhibited proliferation and migration, and also induced apoptosis. TMPO-AS1 located in the cytoplasm and promoted RAB14 expression by absorbing miR-577. RAB14 overexpression or miR-577 knockdown restored the suppressing effect of TMPO-AS1 knockdown on the biological behavior of CC cells. CONCLUSIONS: The present study has revealed a novel TMPO-AS1/miR-577/RAB14 regulatory axis in the pathogenesis of CC, highlighting TMPO-AS1 as a promising therapeutic target for CC patients.

Tumoricidal activity of combining the agonistic DR5 antibody D-6 with cisplatin in C30 cisplatin-resistant ovarian cancer in vitro and in vivo.

A previous study by our group reported that the agonistic DR5 antibody D-6 was capable of triggering apoptosis in A2780 cisplatin-sensitive ovarian cancer cells and that this marked effect was enhanced by cisplatin in vitro. The present study examined whether D-6 and cisplatin may exert the same anti-tumor effect on C30 cisplatin-resistant ovarian cancer cells, and the underlying mechanisms were investigated. D-6 exhibited an apoptosis-inducing effect, increased the cell growth inhibition rate of C30 cells in a dose-dependent manner, induced significant morphological changes characteristic for apoptosis, as observed by electron microscopy, and downregulated the expression of caspase 3, 8 and 9 precursors in C30 cells treated with D-6 at the protein level. All of these effects were evidently enhanced when accompanied by cisplatin. Furthermore, D-6 alone or in combination with cisplatin in the established models of C30 tumor xenografts resulted in a significant repression of tumor growth, and evident apoptosis, as determined by a terminal transferase dUTP nick end labeling assay. In addition, the expression of caspase 3, 8 and 9 precursors in the tumor xenografts was as similar to that found in vitro. In conclusion, the present study suggested that D-6 may serve as a novel anti-tumor agent against C30 cisplatin­resistant ovarian cancer, with the ability to trigger apoptosis via caspase-dependent and ­independent pathways and the potential to decrease the cisplatin resistance of the C30 cell line.

Apoptosis-inducing effect of the DR5 monoclonal antibody, D-6, alone or in combination with cisplatin, on A2780 ovarian cancer cells.

Death receptor 5 (DR5) antibody (D-6) is a monoclonal antibody directed against DR5. The aim of this study was to explore the apoptosis-inducing effects of DR5 (D-6), alone or in combination with cisplatin, on A2780 ovarian cancer cells. The cells were treated with various concentrations of cisplatin and/or DR5 (D-6), or a combination of both. For the control group, the cells were treated only with culture medium. Twenty-four hours after the culture, the morphological changes of each group were observed under an inverted microscope. The cell growth inhibition rates were also analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTT) assays, and the apoptosis was analyzed by flow cytometry. Western blotting analysis was used to detect the intracellular reaction. Our results showed that DR5 monoclonal antibody (D-6) was able to induce the apoptosis and increase the cell growth inhibition rates of ovarian cancer cells in a dose-dependent manner, and the effect was enhanced by cisplatin. There were significant morphological changes, a higher cell growth inhibition rate and apoptosis rate and lesser expression of caspase-3, 8, 9 precursors in the cells treated with both cisplatin and DR5 (D-6). The combination treatment of the DR5 monoclonal antibody (D-6) with cisplatin may be a promising treatment for ovarian cancer.