Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation.

Immune homeostasis is key to guarantee that the immune system can elicit effector functions against pathogens and at the same time raise tolerance towards other antigens. A disturbance of this delicate balance may underlie or at least trigger pathologies. Endocrine disrupting chemicals (EDCs) are increasingly recognized as risk factors for immune dysregulation. However, the immunotoxic potential of specific EDCs and their mixtures is still poorly understood. Thus, we aimed to investigate the effect of bisphenol A (BPA) and benzophenone-3 (BP-3), alone and in combination, on in vitro differentiation of T helper (TH)17 cells and regulatory T (Treg) cells. Naïve T cells were isolated from mouse lymphoid tissues and differentiated into the respective TH population in the presence of 0.001-10 µM BP-3 and/or 0.01-100 µM BPA. Cell viability, proliferation and the expression of TH lineage specific transcription factors and cytokines was measured by flow cytometry and CBA/ELISA. Moreover, the transcription of hormone receptors as direct targets of EDCs was quantified by RT-PCR. We found that the highest BPA concentration adversely affected TH cell viability and proliferation. Moreover, the general differentiation potential of both TH populations was not altered in the presence of both EDCs. However, EDC exposure modulated the emergence of TH17 and Treg cell intermediate states. While BPA and BP-3 promoted the development of TH1-like TH17 cells under TH17-differentiating conditions, TH2-like Treg cells occurred under Treg polarization. Interestingly, differential effects could be observed in mixtures of the two tested compounds compared with the individual compounds. Notably, estrogen receptor ß expression was decreased under TH17-differentiating conditions in the presence of BPA and BP-3 as mixture. In conclusion, our study provides solid evidence for both, the immune disruptive potential and the existence of cumulative effects of real nature EDC mixtures on T cell in vitro differentiation.

Real-world study of lymphadenectomy in patients with advanced epithelial ovarian cancer.

BACKGROUND: The evidence on the role of retroperitoneal lymphadenectomy is limited to less common histology subtypes of epithelial advanced ovarian cancer. METHODS: This retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results Program from January 1, 2010, to December 31, 2019. Patients with stage III-IV epithelial ovarian cancer were included and divided into two groups based on whether they received retroperitoneal lymphadenectomy. The primary outcomes are overall survival (OS) and cause-specific survival (CSS). RESULTS: Among the 10 184 included patients, 5472 patients underwent debulking surgery with retroperitoneal lymphadenectomy, while 4712 patients only underwent debulking surgery. No differences were found in the baseline information between the two groups after propensity score matching. Retroperitoneal lymphadenectomy during debulking surgery was associated with improved 5-year OS (43.41% vs. 37.49%, p < 0.001) and 5-year CSS (46.43% vs. 41.79%, p < 0.001). Subgroup analysis further validate the retroperitoneal lymphadenectomy increased the 5-year OS and CSS in patients with high-grade serous cancer. Although the results were not validated in the less common ovarian cancer (including endometrial cancer, mucinous cancer, low-grade serous cancer, and clear cell cancer), the tendency showed patients with the above four subtypes may benefit from the lymphadenectomy which is restricted for small sample size after propensity score matching. CONCLUSIONS: This study revealed that retroperitoneal lymphadenectomy could further improve the survival outcome during debulking surgery in patients with advanced epithelial ovarian cancer. The conclusion was affected by the histology subtypes of ovarian cancer and further studies are needed to validate the conclusion in less common ovarian cancer.

The fetal outcomes after neoadjuvant platinum and paclitaxel chemotherapy during pregnancy: analysis of three cases and review of the literature.

OBJECTIVE: Data on the outcomes of fetus who are exposed to neoadjuvant platinum and paclitaxel chemotherapy during pregnancy are lacking. METHODS: Relevant data were abstracted from patients in our institution, PubMed, Embase and Cochrane Library databases. The primary assessment was the frequency of fetal death and congenital abnormalities. The secondary assessment was other negative fetal/infant outcomes including FGR, RDS, secondary malignant diseases and other recorded adverse events. RESULTS: Of the three infants in our center who exposed to platinum and paclitaxel chemotherapy during pregnancy, the physical evaluation and qualified Denver Developmental Screening Test showed normal findings at the last follow-up (19-24 months). Hearing evaluation among three children also showed normal findings. Another 34 infants (including a twins) of 21 studies in previous studies who exposed to platinum and paclitaxel chemotherapy during pregnancy were included in the final analysis. Of the 37 infants identified, 24 were exposed to cisplatin plus paclitaxel, and 13 were exposed to carboplatin plus paclitaxel. None of the 37 fetuses was abortion or dead during the pregnancy. 97.3% (36/37) infants were delivered by cesareans and the median gestational ages of delivery were 34.76 weeks (95% CI, 34.08-35.44). 1 fetus showed intrauterine growth restriction and one was found with left-sided ventriculomegaly and hydramnios before chemotherapy. Adverse events occurred in 18.9% (7/37) infants at birth, including two RDS, one hearing loss, one pathological jaundice, one first-degree intraventricular hemorrhage, one erythema, one corresponding to -0.5 standard deviation from average body weight of the same gestational weeks. No reports of neonatal cardiologic abnormalities are reported in these infants after the initiating of chemotherapy. The infant with congenital anomaly died 5 days after birth. During the follow-up, 5.4% (2/37) of the infants were diagnosed with malignant diseases. One retroperitoneal embryonal rhabdomyosarcoma at 5 years old and one acute myeloid leukemia at 22 months of age. 32/37 (86.5%) children were healthy at the end of follow-ups (median 33 months, IQR 15.75-54.25 months). CONCLUSIONS: Our results showed that neoadjuvant platinum and paclitaxel combined chemotherapy was a feasible and safe choice for the management of patients with cervical and ovarian cancer during the second and third trimesters of gestation.