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This study investigated PD-L1 expression in endometrial cancer, its links with prognostic factors, and survival outcomes in 232 patients. Of these, 73 (31.5%) had PD-L1-positive tumors and 159 (68.5%) had PD-L1-negative tumors. PD-L1 expression significantly correlated with adverse prognostic factors. The PD-L1-positive group had higher rates of high-grade tumors (37.0% vs. 19.1%, p = 0.004), deep myometrial invasion (35.6% vs. 24.4%, p = 0.004), lymphovascular space invasion (LVSI) (39.7% vs. 25.6%, p = 0.023), and lymph node metastasis (7.2% vs. 17.1%, p = 0.024) than the PD-L1-negative group. While 5-year progression-free survival (PFS) favored the PD-L1-negative group (94.1% vs. 86.3%), this difference lacked statistical significance (p = 0.139). No significant variations emerged in overall survival (OS) (p = 0.596) or recurrence rates between the groups. Although outcomes lack statistical significance, they suggest a plausible link between PD-L1 and established adverse prognostic factors, such as histological grade, myometrial invasion depth, LVSI, and lymph node metastasis in endometrial cancer. These insights hint at PD-L1’s potential as an informal prognostic indicator, potentially aiding in endometrial cancer patient management.

The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients’ clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH.

This study was performed to evaluate the anticancer effects of tolerable doses of metformin with or without medroxyprogesterone (MPA) in endometrial cancer cells. Cell viability, cell invasion, and levels of matrix metallopeptidase (MMP) and transforming growth factor (TGF)-β1 were analyzed using three human endometrial adenocarcinoma cell lines (Ishikawa, KLE, and uterine serous papillary cancer (USPC)) after treatment with different dose combinations of MPA and metformin. Combining metformin (0, 100, 1000 µM) and 10 µM MPA induced significantly decreased cell viability in a time- and dose-dependent manner in Ishikawa cells, but not in KLE and USPC cells. In KLE cells, metformin treatment alone significantly inhibited cell invasion in a dose-dependent manner. The inhibitory effect of metformin was reversed when 10 µM MPA was combined, which was significantly inhibited again after treatment of MMP-2/9 inhibitor and/or TGF-β inhibitor. Changes of MMP-9 and TGF-β1 according to combinations of MPA and metformin were similar to those of invasion in KLE cells. In conclusion, the anticancer effects of tolerable doses of metformin varied according to cell type and combinations with MPA. Anti-invasive effect of metformin in KLE cells was completely reversed by the addition of MPA; this might be associated with MMP-9 and TGF-β1.

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28–79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1–6). During the median follow-up of 4.9 months (range, 0.2–35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3–13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3–10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike’s information criterion (AIC) were developed using CBC profiles to calculate individuals’ risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3–183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals’ risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer.

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Efforts have been made to develop bromodomain inhibitors as cancer treatments. Sub-pathways, particularly in ovarian cancer, affected by bromodomain-containing protein (BRD) remain unclear. This study verified the antitumor effects of a new drug that can overcome OPT-0139-chemoresistance to treat ovarian cancer. A mouse xenograft model of human ovarian cancer cells, SKOV3 and OVCAR3, was used in this study. Cell viability and proliferation were assessed using MTT and ATP assays. Cell cycle arrest and apoptosis were determined using flow cytometry. BRD4 and c-Myc expression and apoptosis-related molecules were detected using RT-PCR and real-time PCR and Western blot. We confirmed the OPT-0139 effect and mechanism of action in epithelial ovarian cancer. OPT-0139 significantly reduced cell viability and proliferation and induced apoptosis and cell cycle arrest. In the mouse xenograft model, significant changes in tumor growth, volume, weight, and BRD4-related gene expression were observed, suggesting the antitumor effects of BRD4 inhibitors. Combination therapy with cisplatin promoted apoptosis and suppressed tumor growth in vitro and in vivo. Our results suggest OPT-0139, a BRD4 inhibitor, as a promising anticancer drug for the treatment of ovarian cancer by inhibiting cell proliferation, decreasing cell viability, arresting cell cycle, and inducing apoptosis.