RESUMO
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 ß-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.
Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Paclitaxel/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/genética , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Feminino , Variação Genética , Humanos , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismoRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Assuntos
Placenta , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Placenta/diagnóstico por imagem , Pré-Eclâmpsia/epidemiologia , Estudos Retrospectivos , Estudos Prospectivos , Resultado da GravidezRESUMO
This study aimed to assess the current status of gestational diabetes mellitus (GDM) diagnosis and management, and the demand for a digital healthcare system, in order to develop an optimal digital-based management model for GDM. An anonymous online survey was conducted targeting pregnant/postpartum women (Group W), internal medicine physicians (Group P), and obstetricians (group O) from September 6, 2022 to December 31, 2022. The survey assessed the women's knowledge of GDM and gathered information about healthcare professionals' (HCPs) current GDM management practices. All groups were asked about their acceptance of and demands for a digital healthcare system for GDM. Statistical comparisons between groups were conducted using the chi-square test or Fisher's exact test where appropriate. A total of 168 participants were in Group W, 185 in Group P, and 256 in Group O. Participants from all groups recognized the need for a digital healthcare system for GDM (Group W: 95.8%, Group P: 85.9%, Group O: 60%). However, HCPs showed less willingness to integrate these systems into their clinics than pregnant/postpartum women. Essential features identified were recording blood glucose levels and insulin, along with automatic data linkage from self-monitoring devices. Group W showed a higher preference for lab test access, search functionality, and fetal weight assessment than groups P and O (all P < .0001), while Groups P and O had a greater preference for recording insulin and maternal body weight compared to Group W (P = .0141 and .0023, respectively). Both pregnant/postpartum women and HCPs acknowledged the benefits of utilizing a digital healthcare system for managing GDM. However, there were differences in perspectives among these groups.
Assuntos
Diabetes Gestacional , Humanos , Diabetes Gestacional/terapia , Feminino , Gravidez , Estudos Transversais , Adulto , Inquéritos e Questionários , Pessoal de Saúde , TelemedicinaRESUMO
Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.
Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Sangue Fetal , Retardo do Crescimento Fetal , Exposição Materna , Fenóis , Humanos , Feminino , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/sangue , Disruptores Endócrinos/urina , Estudos Prospectivos , Gravidez , Retardo do Crescimento Fetal/induzido quimicamente , Adulto , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/urina , Compostos Benzidrílicos/sangue , Fenóis/urina , Fenóis/efeitos adversos , Fenóis/sangue , Exposição Materna/efeitos adversos , Sangue Fetal/química , Fluorocarbonos/sangue , Fluorocarbonos/efeitos adversos , Ácidos Ftálicos/urina , Ácidos Ftálicos/efeitos adversos , Caprilatos/sangue , Caprilatos/efeitos adversos , Insuficiência Placentária , República da Coreia/epidemiologia , Seul/epidemiologiaRESUMO
Background: Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) was introduced in 2012, but the technique is not yet widely used for ovarian cystectomy. We aim to introduce a new gasless ovarian hemostatic suturing technique for ovarian cystectomy using vNOTES. Methods: We conducted a prospective study using a novel technique for vNOTES ovarian cystectomy. Our vNOTES port (a wound retractor and a disposable glove) was inserted transvaginally through a posterior colpotomy. After ovarian cystectomy, removal of the glove created a gasless state. Hemostatic suturing of the ovary was performed through a vaginal speculum inserted through the wound retractor, under direct observation. Results: Twenty ovarian cystectomies were performed through vNOTES at our institution between June 2019 and February 2020. The mean patient age was 34.2 years (range, 24-51 years). Four patients (20%) underwent bilateral cystectomy and 16 patients (80%) underwent unilateral cystectomy. The mean operative time was 58.7 minutes (bilateral, 57.5 minutes; unilateral, 58.9 minutes), and the mean ovarian hemostatic suturing time was 4.3 minutes (bilateral, 5 minutes; unilateral, 4.1 minutes). Ten patients (50%) received additional medication for pain control within 30 minutes of surgery. All patients were discharged within 24 hours, and 11 were discharged within 12 hours. Conclusion: The gasless hemostatic suturing technique for vNOTES, using a speculum to observe the suturing process, is easy to perform and allows for rapid ovarian hemostasis.