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Aim To evaluate the effects of the combination of calcitriol and chemotherapy and to identify the molecular mechanisms underlying the effect of calcitriol on ovarian cancer cells. Materials and methods SKOV-3 cells were treated with calcitriol and cisplatin, and their effects alone and in combination in a dose-dependent manner were compared. Cell viability, cell proliferation, and apoptosis were assessed using the following assays: PrestoBlue, intracellular adenosine triphosphate, caspase-3/7 activity, annexin V, and immunoblotting, respectively. Results Calcitriol alone caused dose-dependent inhibition of cell survival and proliferation, and induced apoptotic cell death of SKOV-3 cells. We confirmed that the expression of vitamin D receptor was increased in a dose-dependent manner by calcitriol. Combination treatment using calcitriol at a physiological concentration of 10-100 nM plus cisplatin significantly suppressed cell survival and induced apoptosis. Furthermore, when calcitriol was administered alone, the activity of vascular endothelial growth factor decreased in a dose-dependent manner, and when combined with cisplatin, activity was more suppressed. Conclusion In SKOV-3 ovarian cancer cells, calcitriol plus cisplatin exerted greater antiproliferative, apoptotic, and anti-angiogenic effects than cisplatin alone. Adding calcitriol to platinum-based chemotherapy might be beneficial to patients with ovarian cancer.

Background/aim To investigate the abundance of programmed death-ligand 1 (PD-L1) expression and identify rational candidates for anti-PD-1/PD-L1 immunotherapies in cervical cancer. Patients and methods In 27 patients with FIGO stage IB1-IIA cervical cancer, paraffin-embedded tumors were immunohistochemically stained with PD-L1 antibody. The correlation of tumoral PD-L1 expression with clinicopathological factors and survival outcomes were evaluated. Results Overall, PD-L1 expression was primarily detected in 12 (44.4%) patients. All tumors with PD-L1 expression were squamous cell carcinomas (SqCC). In subgroup analysis of SqCC, higher PD-L1 expression was associated with low preoperative serum SqCC antigen level (p=0.030) and no parametrial invasion (p=0.048). The 5-year progression-free survival (83.3% vs. 50.0%. p=0.136) and overall survival rates (90.9% vs. 83.3%, p=0.615) were superior in patients with PD-L1 expression that in those without PD-L1 expression; however, neither was significant. Conclusion Patients with SqCC and favorable clinicopathological factors could be candidates for anti-PD-1/PD-L1 immunotherapy in cervical cancer.

The expression patterns of the key DNA damage response-related proteins, ataxia-telangiectasia and tfiih/ner complex atp-dependent 5'-3' dna helicase subunit rad3 (RAD3)-related (ATR) and ataxia-telangiectasia-mutated (ATM) proteins in ovarian cancer are not well-known. This study aimed to evaluate the expressions of ATR and ATM proteins, and to investigate their clinical significance in epithelial ovarian carcinoma (EOC).The expressions of nuclear/cytoplasmic Ser428-phosphorylated ATR (p-ATR) and Ser1981-phosphorylated ATM (p-ATM) were evaluated by immunohistochemistry in 100 patients with EOC. The clinical significances of p-ATR and p-ATM protein expression were evaluated in terms of tumor progression and survival.Low expression of cytoplasmic p-ATR was significantly associated with advanced stage, serous histology, large residual mass, and high preoperative serum CA125 level. Univariate survival analysis revealed that low expression of cytoplasmic p-ATR protein was significantly associated with poor disease-free survival and poor overall survival.Our study demonstrates that cytoplasmic ATR protein might serve as a prognostic biomarker for patients with EOC.

No human papillomavirus (HPV) type-specific guidelines exist for managing cases of patients with atypical squamous cells of undetermined significance (ASC-US) by cervical cytology. Herein, we investigated ASC-US triage strategies using HPV genotyping to identify methods that are potentially superior to triage, using Hybrid Capture 2.In this retrospective cohort study, 144 Korean women with ASC-US cytology underwent HPV genotyping and punch biopsy under colposcopy/endocervical curettage. We created a model for ASC-US triage using HPV genotyping in these patients. The sensitivity of the final triage criterion was internally validated using bootstrapping.Positivity for HPV16, 18, 31, 33, 52 and 58 genotype corresponded to a referral rate of 63% and detection of 92% of cases of cervical intraepithelial neoplasia grade 2 or higher. The referral and detection rates for such cases increased in proportion to the number of high-risk HPV types. The sensitivity of genotyping for HPV16, 18, 31, 33, 52 and 58 was 92%.The study demonstrates that HPV genotyping of specific HR-HPV types may be an effective strategy in ASC-US triage and may replace conventional HPV tests.

To assess the feasibility of less radical surgery in patients with incidentally-detected cervical cancer at simple hysterectomy.High-risk factors (HFs) were evaluated in 104 patients who underwent radical hysterectomy and lymphadenectomy for the treatment of stage IA1-IB1 cervical cancer according to intermediate-risk factors (IFs).Thirty-three patients without IFs had no HFs. As the number of IFs increased, the number of HFs increased (p=0.009). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for parametrial involvement (hazard ratio, 31.3; 95% confidence interval, 1.6-599.4; p=0.022). An absence of IFs was associated with a longer progression-free survival than the presence of IFs in the subgroup analysis of favorable histologies (p=0.044).HFs could be excluded in stage IA1-IB1 cervical cancer without IFs. Omitting parametrectomy seems a feasible option for selected patients with incidentally-detected early-stage cervical cancer at simple hysterectomy, without IFs.