Sohyeon Jeong

Establishment of a rabbit uterine cancer model using VX2 tumor fragments

Background Preclinical uterine cancer models using the rabbit VX2 system have been described in previous studies; however, they often involve complex procedures such as cell culture, uterine suturing, or imaging validation. This study aimed to establish a technically simple and reproducible rabbit model of uterine cancer using VX2 tumor fragments. Methods We established a rabbit uterine cancer model by injecting minced VX2 tumor tissue into the endometrium of New Zealand White rabbits. We first generated VX2 tumors in donor rabbits via subcutaneous thigh injection and harvested them after three weeks. Recipient rabbits were assigned to two cohorts with scheduled assessments at 14 days or 4 weeks post-implantation. Tumor formation was assessed at each time point by intraoperative inspection and histopathological analysis. Results In the initial 14-day cohort (n = 8), all rabbits developed well-defined uterine tumors without perioperative complications. Histological analysis confirmed viable tumor growth. No lymph node metastasis or distant spread was observed at the 14-day endpoint. In a separate, extended 4-week cohort (n = 8), all rabbits also developed uterine tumors. This cohort demonstrated tumor progression, with 75% exhibiting retroperitoneal lymph node metastasis, and 37.5% showing peritoneal metastasis. Conclusion This study demonstrates the feasibility and reproducibility of a simplified VX2 uterine cancer model using tumor fragments. Furthermore, the model replicates metastatic progression, including retroperitoneal lymph node and peritoneal metastasis, by 4 weeks. The model may serve as a reliable platform for future preclinical studies involving uterine tumor biology and metastatic progression.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2

This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. ClinicalTrials.gov Identifier: NCT02139267.

Long-term risks of coronary heart disease and cerebrovascular disease in ovarian, uterine and cervical cancer survivors: a nationwide study in Korea

Only few studies have evaluated the incidence of coronary heart disease (CHD) and cerebrovascular disease (CVD) among gynaecologic cancer survivors. We selected 26,880 gynaecologic cancer patients who underwent health check-ups within 2 years after diagnosis using the Korean National Health Insurance Service Database. They were compared with 79,830 non-cancer controls. Cox regression models were used to estimate hazard ratios (HRs). There was no significant relationship between gynaecologic cancer survivors and CHD or CVD events. However, 10 years after diagnosing cancers, the risk of angina increased in cancer survivors (adjusted HR = 1.193, 95% CI: 1.013-1.406). After 1 year of diagnosis, cancer patients with no initial comorbidities showed an increased risk of all CHD and CVD events (adjusted HR = 1.101, 95% CI: 1.020-1.189) and CHD alone (adjusted HR = 1.168, 95% CI: 1.055-1.293) compared with controls. CHD risk was also higher in the cancer group with no comorbidities after 10 years of diagnosis (adjusted HR = 1.284, 95% CI: 1.020-1.615). Overall, the risk of CHD or CVD did not increase in gynaecologic cancer survivors. However, cancer patients without any comorbidities showed a higher risk of CHD compared with control, the risk persisting until 10 years after cancer diagnosis.Impact Statement