Tumor invasion and metastasis are complex biological processes. Matriptase and its endogenous inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1) are involved in invasion and metastasis. To evaluate the ratio of matriptase/HAI-1 and their potential therapeutic value in ovarian cancer, HO-8910 human ovarian cancer cells and the homologous high-metastatic HO-8910PM cells were used as in vitro cellular models ovarian cancer. The invasive and metastatic abilities, and the expression of matriptase and HAI-1 in these cells were detected using scratch assays, Transwell chamber assays, reverse transcription-quantitative polymerase chain reaction, western blotting and fluorescent immunocytochemistry. Following infection with lentivirus-mediated matriptase-targeting small interfering RNA (siRNA), cell cycle progression and apoptosis were also analyzed. The migration distance and number of invading HO-8910PM cells were significantly increased compared with HO-8910 cells. HO-8910PM cells exhibited a significantly higher ratio of matriptase/HAI-1 mRNA levels compared with HO-8910 cells (0.51 vs. 0.24, ~2.2 fold increase). Compared with HO-8910 cells, the matriptase mRNA level was increased by ~3.6 fold in HO-8910PM cells, whereas the HAI-1 mRNA level was increased by ~1.7 fold. Similar increases in protein expression levels were also observed in HO-8910PM cells compared with HO-8910 cells. Migration and invasiveness were positively correlated with matriptase expression level (r=0.994, P<0.01) and the ratio of matriptase/HAI-1 (r=0.929, P<0.01). Downregulation of matriptase using siRNA resulted in inhibition of the invasive and metastatic abilities of HO-8910PM cells, cell cycle arrest in the G0/G1 phase and increased apoptosis. The present study demonstrated that ovarian cancer cell metastasis and invasion were more dependent on upregulation of matriptase levels than downregulation of HAI-1. Matriptase may be a potential adjuvant therapeutic target for inhibiting ovarian cancer invasion and metastasis.
Background: PGC-1α and ERRα are closely related to tumor formation and progression. However, the mechanism underlying the involvement of PGC-1α/ERRα in regulating invasion and migration in endometrial cancer remains to be explored. Results: Elevated levels of PGC-1α and ERRα were associated with advanced myometrial invasion, and PGC-1α and Vimentin expression was related to the depth of myometrial invasion in premenopausal endometrial cancer. Silencing of PGC-1α reduced ERRα activation and inhibited epithelial-mesenchymal-transition phenotypes, resulting in significant inhibition of invasion and migration. Overexpression of ERRα led to enhanced PGC-1α expression and increased activity of TFEB, promoting epithelial-mesenchymal-transition in endometrial cancer cells. Conclusions: PGC-1α and ERRα induce the epithelial-mesenchymal-transition therefore invasion and migration in endometrial cancer, and may be novel biomarkers to predict the risk of advanced myometrial invasion. Methods: PGC-1α, ERRα, and vimentin expression was analyzed in tissue microarrays using immunohistochemistry. PGC-1α and ERRα expression in endometrial cancer cell lines was investigated using quantitative PCR and western blotting analyses after infection with lentivirus-mediated small interfering RNA (siRNA) targeting PGC-1α (siRNA-PGC-1α) or overexpressing ERRα. E-cadherin and vimentin levels were determined using western blotting and cell immunouorescence analyses. Cell migration and invasiveness were evaluated using scratch and trans-well chamber assays.
The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA (P < 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased (P < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased (P < 0.001) due to the down-regulation of matriptase and HAI-1 upon increasing cisplatin concentration. However, a slight increase in matriptase and HAI-1 expression was observed in cells treated with low cisplatin concentration (P = 0.01). Moreover, matriptase expression was associated with metastasis and invasiveness. Down-regulation of matriptase by specific Ma-SiRNA or non-specific cisplatin in matriptase/HAI-1–positive endometrial cancer cells showed promising therapeutic features.
Background Previous studies have shown that the incidence of ectopic pregnancy (EP) is increasing in China. It is unclear, however, whether the incidence of EP has changed after the implementation of the universal two-child policy in the context of China’s aging population and declining fertility rate. Methods Data concerning EP from January 2011 to December 2020 were collected from the hospital’s electronic medical records, which included the annual number of delivery, caesarean section rate, ectopic pregnancies, treatment of tubal pregnancy, and average costs and length of hospitalization. Trends of the EP incidence were analysed and annual percentage change (APC) was calculated using connected point regression analyses. Results A total of 9499 cases of EP were collected, among which caesarean scar pregnancy (CSP) accounts for the second highest (6.73%). The EP per 100 deliveries revealed a downward trend, from 7.60% in 2011 to 4.28% in 2020 with an APC of -1.87 (P < 0.05). The maternal age was increased, especially after the implementation of the universal two-child policy. The constituent ratio for the advanced maternal age (≥ 35) and the caesarean section rate, but not the CSP, were also increased. Laparoscopic salpingectomy was the main surgical method, whereas the adoption of laparotomy and laparoscopic salpingostomy was decreasing year by year. Conclusions Although no obvious effect of the two-child policy on EP has been observed under the conditions of this study, the change in EP especially in advanced-age women after the policy implementation needs further evaluation. A decreased caesarean section rate, in primipara is beneficial to reducing the CSP.
This study aimed to investigate the clinical application value of the 5-fluorouracil (5-FU) sustained-release particles implanted along the cardiac tangent direction into malignant pericardial effusion (MPCE). A total of 81 MPCE patients underwent pericardiocentesis, and were implanted with 5-FU sustained-release particles into the pericardial cavity under ultrasound guidance. The puncturing path was along the cardiac tangent direction. Ultrasound examinations were performed every week, and the efficacy was evaluated 4 weeks after treatment. The 45 patients who were treated with pericardial catheter drainage and simultaneous intracavitary chemotherapy were used as the control group. The success rate of pericardiocentesis was 100%. Ultrasound reviews performed 4 weeks after treatment showed that 71 cases achieved complete remission and eight cases achieved partial remission, while treatment was completely ineffective in two cases. The total remission rate was 97.53%, which was significantly higher than that of the control group (77.78%, p < 0.01). The implantation of 5-FU sustained-release particles along the cardiac tangent direction was safe, and demonstrated good efficacy and fewer adverse reactions. Thus, this method could be ideal for the treatment of MPCE.
Background: Previous studies have shown that the incidence of ectopic pregnancy (EP) is increasing in China. It is unclear, however, whether the incidence of EP has changed after the implementation of the universal two-child policy in the context of China's aging population and declining fertility rate. Methods: Data with respect to EP were collected from the hospital's electronic medical records from January 2011 to December 2020, which included the annual number of delivery, cesarean section rate and ectopic pregnancies, treatment of tubal pregnancy, and averaged costs and length of stay in the hospital. Trends were analyzed and annual percentage change (APC) was calculated using connected point regression analyzes. Results: A total of 9499 cases of EP were collected, among which cesarean scar pregnancy (CSP) account for the second most (6.73%). The EP per 100 deliveries revealed a downward trend, from 7.60% in 2011 to 4.28% in 2020 with an APC of -1.87 (P < 0.05). The maternal age was increased, especially after the implementation of the universal two-child policy. Constituent ratio for the advanced maternal age (≥ 35) and the cesarean section rate, but not the CSP, were also increased. Laparoscopic salpingectomy was the main surgical method, whereas the adoption of laparotomy and laparoscopic salpingostomy was decreasing year by year. Conclusions: Although the implementation of the universal two-child policy increased the number of births, the proportion of older mothers and cesarean section rate, this policy change seems to be less effective on EP.
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