Acquired paclitaxel (PTX) resistance limits its effectiveness and results in advanced cancer progression. This review investigated whether the inhibition of phosphatidylinositol 3-kinase (PI3K) signaling overcomes paclitaxel resistance in cervical cancer. It was established paclitaxel-resistant cell lines (PTX-R ME180/PTX-R HeLa) and determined the combination index for paclitaxel and PI3K inhibitors (BYL-719/ LY294002) by tetrazolium dye assay. Flow cytometry was used to detect the cell cycle and apoptosis. Migration and invasion were explored by wound healing and transwell assays. Genes related to multiple pathways were assessed by a western blot. It was found that the PI3K pathway was significantly activated in paclitaxel-resistant HeLa and ME180 cells compared to parental cells. PTX + PI3K inhibitor combined therapy showed a synergistic effect by strengthening paclitaxel-induced S and G2M arrest in PTX-R cell sublines by the inactivation of cyclin A1, cyclin B1, cyclin E, and Cdc2 expression. Moreover, combination therapy significantly enhanced drug sensitivity and apoptosis through the activation of Bax, and cleavage of poly-(ADP-ribose) polymerase compared with paclitaxel alone. In addition, PI3K inhibition also suppressed tumor migration and invasion by targeting β-catenin and matrix metalloproteinase-2/9. The authors suggest that the combination of a PI3K inhibitor with paclitaxel may enhance antitumor activity through a cascade of PI3K signaling events.
Objective: The study aimed to investigate the clinical outcomes of fetuses diagnosed with isolated mega cisterna magna in utero. Methods: A multicenter retrospective cohort study was conducted across 18 university hospitals from 2010 to 2019. Cases diagnosed with isolated mega cisterna magna, defined as a cisterna magna >10 mm with a normal cerebellar vermis and no cystic dilation of the fourth ventricle, were included. Cases with other central nervous system (CNS) anomalies, extra–central nervous system anomalies, chromosomal abnormalities, or congenital infections were excluded. Maternal demographics, prenatal findings, delivery outcomes, and postnatal outcomes were analyzed. Results: The mean gestational age at initial diagnosis was 28.6 ± 3.9 weeks, and the mean anteroposterior diameter of the cisterna magna was 12.5 ± 3.2 mm. Of the 71 cases initially assessed, 48 (67.6%) showed self-regression in utero. Postnatally, 13 cases (18.3%) had persistent isolated mega cisterna magna, whereas 10 cases (14.1%) were diagnosed with other central nervous system anomalies. Among the persistent isolated mega cisterna magna cases, one child exhibited delayed neurodevelopment. There was a higher incidence of isolated mega cisterna magna in male fetuses, which exhibited a significantly larger mean cisterna magna diameter compared with female fetuses ( P = .045). Conclusion: Male fetuses exhibited a higher incidence of isolated mega cisterna magna compared with female fetuses and had larger anteroposterior diameters of the cisterna magna. The study demonstrated favorable neurodevelopmental outcomes associated with isolated mega cisterna magna, with self-regression observed in two-thirds of the cases. However, consecutive prenatal and postnatal evaluations for additional central nervous system or extra–central nervous system malformations need to be performed, considering the differences between prenatal and postnatal diagnoses.
2 January 2024 in The Journal of Maternal-Fetal & Neonatal Medicine
The relationship between placental location in pregnancies without previa and adverse pregnancy outcomes has not been well studied. Additionally, the impact of abnormal cord insertion sites remains controversial. Therefore, the objective of this study was to explore the adverse outcomes associated with placental location and abnormal cord insertion in nulliparous women and to assess their impact on pregnancy outcomes. This retrospective cohort study was conducted at a single tertiary hospital between January 2019 and June 2022. The study included nulliparous women with singleton pregnancies who delivered live infants and had available data on placental location and umbilical cord insertion site from a second- or third-trimester ultrasound. Placental location was categorized as anterior or posterior using transabdominal ultrasonography. The association between placental location/cord insertion site and pre-eclampsia was evaluated using multivariate logistic regression analysis. We compared the area under the curve to evaluate the impact of placental location and cord insertion site on pre-eclampsia. A total of 2219 pregnancies were included in the study. Pre-eclampsia occurred significantly more frequently in the anterior group than in the posterior group (8.21% vs. 3.04%, p < .001). In multivariate analysis investigating the association between placental location and pre-eclampsia, anterior placenta and marginal cord insertion showed increased odds ratios for pre-eclampsia of 3.05 (95% confidence interval [CI] 1.68-6.58) and 3.64 (95% CI 1.90-6.97), respectively. Receiver operating characteristic (ROC) curves were constructed to predict pre-eclampsia using independent factors from multivariate analyses. Model I, including maternal age, pre-pregnancy body mass index, in vitro fertilization, chronic hypertension, overt diabetes, kidney disease, and hematologic diseases, achieved an area under the ROC curve of 0.70 (95% CI 0.65-0.75). Adding cord insertion site and placental location to the model (Model II) improved its predictive performance, resulting in an area under the ROC curve of 0.749 (95% CI 0.70-0.79, p = .02). Anterior placenta and marginal cord insertion were associated with an increased risk of pre-eclampsia. Further studies on prospective cohorts are necessary to validate these findings.
Gestational diabetes mellitus (GDM) requires lifestyle changes that may alter exposure to endocrine-disrupting chemicals (EDCs). This study aimed to assess maternal and fetal exposure to EDCs—including bisphenol-A (BPA), monoethyl phthalate (MEP), and perfluorooctanoic acid (PFOA)—during the COVID-19 pandemic and to evaluate their association with fetal birthweight. Maternal urine (second and third trimester) and paired cord blood samples were analyzed from 58 GDM and 118 non-GDM pregnancies using UPLC-MS/MS. Significant correlations were found between maternal urine and cord blood levels of BPA and MEP. Cord blood BPA levels were significantly lower in GDM mothers (0.35 vs. 0.72 μg/L, p < 0.05), suggesting reduced exposure due to dietary interventions. However, maternal urinary BPA levels in GDM pregnancies were positively associated with fetal birthweight (β = 2.69, p < 0.05), indicating increased susceptibility to obesogenic effects. PFOA was present in all cord blood but only 41% of maternal urine samples. These findings underscore the dual impact of GDM-related lifestyle changes: reduced EDC transfer to the fetus, yet persistent metabolic vulnerability.
17 October 2026 in Journal of Korean Medical Science
Background and Objectives: Twin pregnancies carry a high risk of preterm birth, and cerclage for a short or dilated cervix is typically placed before 24 weeks. Its use at or after 24 weeks is less well characterized in twins. Materials and Methods: We describe the perinatal course of twin pregnancies that underwent cervical cerclage at 24–32+0 weeks at three university hospitals in South Korea between 2015 and 2024, with pregnancies treated before 24 weeks as a descriptive reference. Entry into the late group required remaining undelivered at 24 weeks without prior cerclage, so the groups do not share a common baseline and were not compared. Results: Eighteen pregnancies received cerclage at 24–32+0 weeks (median 26.3 weeks), and 25 received it before 24 weeks. In the late group, delivery occurred at a median of 34.1 weeks (IQR 31.7–35.4) after a mean cerclage-to-delivery interval of 45.8 days (95% CI 34.7–56.9). No fetal, neonatal, or perinatal death occurred (0 of 36 fetuses in 18 pregnancies; 95% CI 0.0–17.6%, calculated on the 18 pregnancies). NICU admission was 83.3% (95% CI 62.3–93.8), and adverse neonatal morbidity was 55.6% (95% CI 34.2–75.0). Conclusions: No perinatal death was recorded in this descriptive series. Because no untreated control group was available, these findings do not establish efficacy but provide a real-world basis for future prospective controlled trials.