Hypoxia-induced miR-181a-5p up-regulation reduces epirubicin sensitivity in breast cancer cells through inhibiting EPDR1/TRPC1 to activate PI3K/AKT signaling pathway.

Breast carcinoma (BC) ranks as a predominant malignancy and constitutes the second principal cause of mortality among women globally. Epirubicin stands as the drug of choice for BC therapeutics. Nevertheless, the emergence of chemoresistance has significantly curtailed its therapeutic efficacy. The resistance mechanisms to Epirubicin remain not entirely elucidated, yet they are conjectured to stem from diminished tumor vascular perfusion and resultant hypoxia consequent to Epirubicin administration. In our investigation, we meticulously scrutinized the Gene Expression Omnibus database for EPDR1, a gene implicated in hypoxia and Epirubicin resistance in BC. Subsequently, we delineated the impact of EPDR1 on cellular proliferation, motility, invasive capabilities, and interstitial-related proteins in BC cells, employing methodologies such as the CCK-8 assay, Transwell assay, and western blot analysis. Our research further unveiled that hypoxia-induced miR-181a-5p orchestrates the regulation of BC cell duplication, migration, invasion, and interstitial-related protein expression via modulation of EPDR1. In addition, we identified TRPC1, a gene associated with EPDR1 expression in BC, and substantiated that EPDR1 influences BC cellular dynamics through TRPC1-mediated modulation of the PI3K/AKT signaling cascade. Our findings underscore the pivotal role of EPDR1 in the development of BC. EPDR1 was found to be expressed at subdued levels in BC tissues, Epirubicin-resistant BC cells, and hypoxic BC cells. The overexpression of EPDR1 curtailed BC cell proliferation, motility, invasiveness, and the expression of interstitial-related proteins. At a mechanistic level, the overexpression of hypoxia-induced miR-181a-5p was observed to inhibit the EPDR1/TRPC1 axis, thereby activating the PI3K/AKT signaling pathway and diminishing the sensitivity to Epirubicin in BC cells. In summation, our study demonstrates that the augmentation of hypoxia-induced miR-181a-5p diminishes Epirubicin sensitivity in BC cells by attenuating EPDR1/TRPC1 expression, thereby invigorating the PI3K/AKT signaling pathway. This exposition offers a theoretical foundation for the application of Epirubicin in BC therapy, marking a significant contribution to the existing body of oncological literature.

Fetal echocardiographic screening in twins for congenital heart diseases.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital disorder at birth. Yagel and colleagues's method of heart examination has been proved valuable in finding CHD prenatally in single pregnancies. The aim of this study was to analyze the frequency of CHD in twin pregnancies and the sensitivity of the method. METHODS: A total of 1103 pregnant women with twins were enrolled in this study, including 127 cases with high-risk for CHD. Five transverse ultrasound measurements were used for fetal heart examination, including the upper abdomen view, four-chamber view, five-chamber view, pulmonary artery bifurcation view, and three-vessel view. In the fetuses who were diagnosed with CHD and whose parents requested termination of the pregnancy, autopsy of the fetal heart was performed after an abortion, and a blood sample was collected from the heart for chromosome evaluation. In the other fetuses, a close follow-up was conducted by echocardiography within one year after birth. RESULTS: Antenatally, CHD was found in 12 twins, of which 4 were from the high-risk group (3.15%), and 8 from the low-risk group (0.82%). In 2 pairs of the twins, the two fetuses had a same kind of CHD (one pair had tetralogy of Fallot (TOF), another pair had rhabdomyoma). Another pair had different types of anomaly (one fetus had TOF, and the other duodenal atresia with a normal heart). Termination of pregnancy was performed in these three pairs and the autopsy of the fetal heart confirmed the ultrasound findings. In the other 9 pairs, CHD was detected in one fetus, and a normal heart in the others. In the cases who received chromosome evaluation, 2 had abnormal chromosomes. During the follow-up after birth, heart examinations confirmed the prenatal diagnosis in 7 of the 9. The diagnosis of CHD was missed antenatally in 2 pairs of twins. In both the cases, one fetus was normal, and the other was confirmed as having CHD after birth (small ventricle septum defect in one, and persistent open ductus arteriosus in the other). Thus, the total frequency of CHD was 16 (7.3/1000), which was similar to that in single pregnancies. The sensitivity of fetal echocardiography was 87.5% and the specificity was 100%. CONCLUSIONS: The frequency of CHD is the same in twin as in single pregnancies. Systemic ultrasound scanning with five transverse views is effective in diagnosing fetal CHD in twin pregnancies.

[Prenatal diagnosis of congenital fetal heart abnormalities in twins by Yagel's heart examination method].

OBJECTIVE: To investigate the value and clinical significance of congenital heart diseases (CHD) detection in twins. METHODS: A total of 1103 twins were included in this study (127 twins were at high risk for CHD). The fetal hearts were scanned by ultrasound using Yagel's heart examination method. Autopsies were done when the pregnancy was terminated. And blood samples from fetal hearts or umbilical veins were used to evaluate fetal chromosomes. A close follow-up was conducted for normal heart cases and another heart examination was done within three months after birth. RESULTS: (1) 12 twins (1.09%, 12/1103) had CHD. Among them, 4 cases were from the high risk for CHD group (33.3%, 4/12), and 8 cases (66.7%, 8/12) were from the low risk pregnancy group. (2) Two twins suffered from the same CHD (one pair were both TOF, and the other pair were both rhabdomyoma). One pair of twins had different abnormalities (one baby was TOF, and the other was duodenal atresia with a normal heart). All three pairs of twins chose termination and autopsies were conducted. Unanimous conclusions between prenatal ultrasound and autopsy were obtained. Nine twins were CHD in one baby and a normal heart in the other baby. Seven of them had the same conclusion after delivery. (3) Two twins with CHD were found with fetal abnormal chromosome. (4) 1091 cases were not found having any abnormality, however, one fetus from one twin pair was diagnosed with ventricular septal defect (VSD) with abnormal chromosome after birth, and one fetus from another twin pair had patency of ductus arteriosus after birth. (5) The sensitivity of Yagel's heart examination was 82.4% and specificity was 100% in twins. CONCLUSION: Yagel's heart examination is an effective and time-saving method to scan fetal hearts in twins.