Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ.

OBJECTIVE: To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. METHODS: Patients diagnosed with AIS after CC during 2007-2021 were identified by computerized databases at Women's Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. RESULTS: Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. CONCLUSION: CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

RAI3 knockdown enhances osteogenic differentiation of bone marrow mesenchymal stem cells via STAT3 signaling pathway.

Bone marrow mesenchymal stem cells (BMSCs), which have multipotential differentiation and self-renewal ability, have been becoming an attractive source of seed cells for bone tissue engineering. Nonetheless, the precise underlying mechanisms of osteogenesis of BMSCs have not been fully understood. Retinoic acid-induced gene 3 (RAI3) has been found to play important roles in mesenchymal stem cells (MSCs) adipogenesis in our previous study. However, its function in the osteogenic differentiation of BMSCs remains unknown. In this study, we found that RAI3 was significantly reduced in osteogenically differentiated BMSCs; RAI3 knockdown promoted osteogenesis of BMSCs both in vitro and in vivo. Moreover, we found RAI3 knockdown significantly upregulated the expression level of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and AG-490 which can inhibit the STAT3 signaling reversed the enhancing effect of RAI3 knockdown on the osteogenic differentiation of BMSCs. These results suggest that RAI3 plays important roles in BMSCs osteogenesis with an involvement of the STAT3 signaling, which might open a new avenue to explore BMSCs osteogenesis for the application of BMSCs in bone regeneration.

Design, synthesis, and biological evaluation of target water-soluble hydroxamic acid-based HDACi derivatives as prodrugs.

Four compounds T1, T2, T3, and T4 were designed and synthesized as Vorinostat and Belinostat derivatives being the target water-soluble prodrugs. The water solubility of Vorinostat derivatives, T1 and T2, exhibited 400- to 600-fold higher than that of Vorinostat, and Belinostat derivatives, T3 and T4, showed 600- to 750-fold higher than that of Belinostat. Four compounds were evaluated for their inhibitory activities against tumor cell lines HT-29 and Hut-78 in the absence or presence of ß-D-glucuronidase. The inhibitory effects of T1 and T2 were comparable to Vorinostat in the presence of ß-D-glucuronidase, but were higher than 10 µM in the absence of ß-D-glucuronidase. Therefore, T1 and T2 are promising candidates for in vivo investigations with high potential to be the target water-soluble prodrugs. IC50 values of Belinostat derivatives T3 and T4 were not affected by ß-D-glucuronidase, but T3 and T4 had the excellent cell proliferation inhibition on Hut-78.