Search

The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) is a molecular classification system that identifies endometrial cancer (EC) into four prognostically distinct subtypes: POLE-mutated, mismatch repair deficiency (MMR-D), p53 wild-type (p53wt), and p53 abnormal (p53abn). However, few reports have applied the ProMisE classifier to EC patients who underwent fertility-preserving treatment (FPT) so far. This study evaluated whether the ProMisE classifier predicted in early-stage EC patients after FPT. We first summarized the three reported outcomes of ProMisE applied to EC patients who received FPT. The hormone-treated patients with EC from 2010 to 2020 in our facility were then analyzed. By sequential immunohistochemistry and Sanger sequencing of POLE according to the ProMisE system, formalin-fixed paraffin-embedded blocks of patients before treatment were collected and classified into POLE-mutated, MMR-D, p53wt, and p53abn subtypes. The primary outcome was a complete response rate after FPT. Thirteen patients were enrolled from our facility, with 3 (3/13) MMR-D, 0 (0/13) POLE, 8 (8/13) p53wt, 1 (1/13) p53abn, and 1 (1/13) failed with DNA amplification. Six (6/8) patients with p53wt, 2 (2/3) patients with MMR-D, and 1 (1/1) patient with p53abn achieved a complete response in 6 months after treatment. The results of our study and the reported outcomes were finally combined. A total of 106 patients who underwent FPT were included. Of these, 23 (21.7%) were classified as MMR-D, 3 (2.8%) as POLE-mutated, 3 (2.8%) as p53abn, and 77 (72.6%) as p53wt. There was no significant difference in the complete response rate (P = 0.152) and recurrence rate (P = 0.174) between MMR-D and p53wt subtypes after FPT. Based on current data, we observed no prognostic significance of the ProMisE classifier in EC patients who underwent FPT. Larger prospective studies are needed to elucidate the precise prognostic meaning of this molecular classifier in these cases.

Objective To evaluate the therapeutic efficacy of REBACIN® in patients with persistent high‐risk HPV (hrHPV) infection. Persistent hrHPV infection is a crucial cause of cervical cancer, for which optimal pharmacological intervention remains unavailable. Methods A retrospective analysis and a meta‐analysis were carried out. The retrospective analysis included 364 patients who were persistently infected with HPV for at least 12 months, between September 2015 and February 2019, and only received the REBACIN® intervention. HPV DNA typing, HC2 hrHPV DNA, and ThinPrep cytologic tests were performed before and after the REBACIN® intervention, to evaluate the therapeutic efficacy. The meta‐analysis included trials evaluating the therapeutic efficacy of interferons. Results After a follow‐up period of 3–6 months, the overall rate of efficacy of REBACIN® was 74.73% (272/364), which was higher than that of interferon (61.50%). The efficacy of REBACIN® was correlated with HPV type (odds ratio [OR] 0.549, 95% confidence interval [CI] 0.367–0.822, P=0.004) and pretreatment cytology (OR 0.358, 95% CI 0.173–0.739, P=0.005). Conclusion REBACIN® is potently efficacious at clearing persistent hrHPV infection; hence, it can serve as an optional intervention for persistent hrHPV infection.

In a previous study we found the expression of epithelial–mesenchymal transition (EMT) biomarkers, including E-cadherin and N-cadherin, was significantly altered in uterine endometrium during embryo implantation via regulation by microRNA (miRNA)-429 and protocadherin-8 (Pcdh8). As a natural continuation of the previous study, the aim of the present study was to explore the role of EMT during embryo implantation and the potential activity of twist basic helix-loop-helix transcription factor 2 (Twist2) in regulating embryo implantation. A pregnancy model was established by naturally mating adult female ICR mice with fertile males. A pseudopregnancy model was established by mating fertile female ICR mice with vasectomised males. An invitro model of embryo implantation was established by the coculture of Ishikawa and JAR spheroids. Endometrial tissue during the peri-implantation period was collected, as were Ishikawa cells, JAR cells and cocultured cells. The expression of EMT markers (E-cadherin, N-cadherin, vimentin and cytokeratin) and Twist2 was detected invivo and invitro using the western blot analysis during embryo implantation. The expression of N-cadherin and vimentin (mesenchymal markers) was upregulated in the invitro implantation model, with downregulation of E-cadherin and cytokeratin (epithelial markers) expression. The expression of N-cadherin, vimentin and Twist2 increased significantly at the implantation sites at the time of implantation (Day 5), whereas the expression of E-cadherin and cytokeratin decreased. Location of Twist2 during embryo implantation was detected by immunohistochemistry (IHC), which revealed that it was extensively expressed in endometrial glandular epithelium and luminal epithelium at implantation sites on Day 5. The effect of the expression of Twist2 on embryo implantation was evaluated by suppressing Twist2 using Twist2-short interference (si) RNA in invivo and invitro models. The numbers of implanted embryos and the implantation rate were compared invivo and invitro. Western blot analysis showed that suppression of Twist2 led to upregulation of E-cadherin and cytokeratin, accompanied by downregulation of N-cadherin and vimentin (P