Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment.

The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.

Prognostic value of ß-Arrestins in combination with glucocorticoid receptor in epithelial ovarian cancer.

Hormones may be key factors driving cancer development, and epidemiological findings suggest that steroid hormones play a crucial role in ovarian tumorigenesis. We demonstrated that high glucocorticoid receptor (GR) expression is associated with a poor prognosis of epithelial ovarian cancer. Recent studies have shown that the GR affects ß-arrestin expression, and vice versa. Hence, we assessed the clinical significance of ß-arrestin expression in ovarian cancer and determined whether ß-arrestin and the GR synergistically have clinical significance and value as prognostic factors. We evaluated the expression of ß-arrestins 1 and 2 and the GR in 169 patients with primary epithelial ovarian cancer using immunohistochemistry. The staining intensity was graded on a scale of 0-4 and multiplied by the percentage of positive cells. We divided the samples into two categories based on the expression levels. ß-arrestin 1 and GR expression showed a moderate correlation, whereas ß-arrestin 2 and GR expression did not demonstrate any correlation. Patients with high ß-arrestin 1 and 2 expression exhibited improved survival rates, whereas patients with low GR expression showed a better survival rate. Patients with high ß-arrestin 1 and low GR levels had the best prognosis among all groups. ß-arrestin is highly expressed in ovarian cancer, suggesting its potential as a diagnostic and therapeutic biomarker. The combination of ß-arrestin and GR demonstrated greater predictive prognostic power than GR expression alone, implicating another possible role in prognostication.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

Postoperative Adjuvant Chemoradiotherapy Versus Chemotherapy Alone for Stage III Endometrial Cancer: A Multicenter Retrospective Study.

INTRODUCTION: We aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer. METHODS: This retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan-Meier method. We also assessed differences in toxicity profiles between the treatment groups. RESULTS: A total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction. CONCLUSION: We confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.

Oncologic safety of minimally invasive surgery in non-endometrioid endometrial cancer.

OBJECTIVE: This study was aimed to compare the oncologic outcomes of patients with non-endometrioid endometrial cancer who underwent minimally invasive surgery with the outcomes of patients who underwent open surgery. METHOD: This is a retrospective, multi-institutional study of patients with non-endometrioid endometrial cancer who were surgically staged by either minimally invasive surgery or open surgery. Oncologic outcomes of the patients were compared according to surgical approach. RESULTS: 113 patients met the inclusion and exclusion criteria. 57 underwent minimally invasive surgery and 56 underwent open surgery. Patients who underwent minimally invasive surgery had smaller tumors (median size, 3.3 vs. 5.2%, p = 0.0001) and a lower lymphovascular space invasion rate (29.8% vs. 48.2%, p = 0.045). In the overall population, the numbers and rate of recurrence were significantly higher in the open surgery group (p = 0.016). In multivariate analysis, disease stage and tumor size were associated with DFS in contrast to surgical procedure. CONCLUSION: Minimally invasive surgery showed similar survival outcomes when compared to open surgery in non-endometrioid endometrial cancer patients, irrespective of disease stage. When minimally invasive surgery is managed by expert surgeons, non-endometrioid histological subtypes should not be considered a contraindication for minimally invasive surgery.

Preoperative neutrophil-to-lymphocyte, platelet-to-lymphocyte and monocyte-to-lymphocyte ratio as a prognostic factor in non-endometrioid endometrial cancer.

Objective: Evaluate the prognostic value of neutrophil-lymphocyte ratio (NMR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) in patients with non-endometrioid endometrial cancer. Method: Laboratory and clinicopathological data from 118 patients with non-endometrioid endometrial cancer who underwent surgical resection between January 2010 and December 2019 were reviewed. NLR, PLR and MLR were analyzed for correlations with recurrence and survival. The receiver operating characteristic (ROC) curves were generated for the NLR, PLR, and MLR. Optimal cut-off values were determined as the points at which the Youden index (sensitivity + specificity - 1) was maximal. Based on the results of the ROC curve analysis, the patients were grouped into high MLR and low MLR groups. Recurrence rate, disease-free survival, and overall survival were compared between the two groups. The prognostic factors were investigated using univariate and multivariate Cox proportional hazards model. Results: The optimal cut-off value of MLR was 0.191 (AUC, 0.718; p < 0.001). Significantly more patients in the high MLR group experienced recurrence (60.3% vs. 15.6%, p < 0.0001) and cancer-related deaths (46.6% vs. 13.3%, p = 0.003). In multivariate analysis, advanced stage and high MLR were independent prognostic factors for disease-free survival and overall survival. Conclusion: Elevated MLR was significantly associated poor clinical outcomes in patients with non endometrioid endometrial cancer. Our findings suggest that MLR may be clinically reliable and useful as an independent prognostic marker for patients with non-endometrioid endometrial cancer.

Secondhand smoke exposure, diabetes, and high BMI are risk factors for uterine cervical cancer: a cross-sectional study from the Korea national health and nutrition examination survey (2010-2018).

BACKGROUND: Human papilloma virus infection and tobacco smoking are the major risk factors for cervical cancer. There are limited studies searching other risk factors for cervical cancer and the results are not consistent. This study investigated the relations between cervical cancer and possible risk factors, including secondhand cigarette smoke exposure, diabetes, body mass index (BMI), and work schedule. METHODS: In this cross-sectional study, 29,557 women completed a cervical cancer questionnaire and were selected using 2010-2018 data from the Korea National Health and Nutrition Examination Survey. Details in secondhand smoke exposure, diabetes, BMI, and work schedule were assessed with participants' health interviews and health-related surveys. RESULTS: Two hundred sixty-two women (0.89%) in the sample were diagnosed with cervical cancer. Domestic secondhand smoke exposure, diabetes, and high BMI significantly increased cervical cancer risk. Respective odds ratios and 95% confidence intervals were: 1.547 (1.042-2.297), 2.156 (1.535-3.027), and 1.036 (1.006-1.067). Weekly work hours, and work schedule were not significantly related to cervical cancer incidence. CONCLUSION: Among Korean women, passive exposure to cigarette smoke at home, diabetes, and high BMI increase risk for cervical cancer.

Prediction of lymphovascular space invasion in patients with endometrial cancer.

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC). Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis. Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the "LVSI index" as "TD×%MMI×tumor grade×cervical stromal involvement." The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200. Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.

Survival rates of patients who undergo minimally invasive surgery for endometrial cancer with cervical involvement.

Objective: Compare the oncologic outcomes of patients with intermediate-risk endometrial cancer who were staged by minimally invasive surgery with the outcomes of patients who underwent open surgery. Methods: Data from 206 patients with intermediate-risk endometrial cancer who were treated between January 2009 and January 2019 were reviewed. The patients' data were retrieved from five institutions. The patients were divided into two groups: those who underwent open surgery and those who underwent minimally invasive surgery. Tumor characteristics, recurrence rate, disease-free survival, and overall survival were compared according to surgical approach. Results: Among the 206 patients included in this study, 76 underwent open surgery (36.9%) and 130 underwent MIS (63.1%). In patients with stage IB endometrial cancer, the recurrence rate, disease-free survival, and overall survival were not significantly different between those who underwent minimally invasive surgery and those who underwent open surgery. However, in patients with stage II endometrial cancer, the recurrence rate was significantly higher among those who underwent minimally invasive surgery (37.5% vs. 5.3%, p = 0.013). Patients with stage II endometrial cancer who underwent minimally invasive surgery had a significantly lower disease-free survival (p = 0.012) than those who underwent open surgery, however, the overall survival (p = 0.252) was similar between the two groups. Conclusion: Minimally invasive surgery results in less favorable survival outcomes than open surgery in patients with stage II endometrial cancer.

Minimally invasive surgery for patients with advanced stage endometrial cancer.

Objective: Compare the oncologic outcomes of patients with advanced stage endometrial cancer who were staged by minimally invasive surgery with the outcomes of patients who underwent open surgery. Methods: Data from 138 patients with advanced stage endometrial cancer who were treated between January 2009 and January 2019 were reviewed. The patients' data were retrieved from five institutions. The patients were divided into two groups: those who underwent open surgery and those who underwent minimally invasive surgery. Tumor characteristics, recurrence rate, disease-free survival, and overall survival were compared according to surgical approach. Results: Among the 138 patients included in this study, 72 underwent open surgery (52.2%) and 66 underwent MIS (47.8%). In patients with advanced-stage endometrial cancer, the recurrence rate was significantly higher among those who underwent open surgery (43.1% vs. 25.8%, p = 0.033). Patients with advanced-stage endometrial cancer who underwent open surgery had a significantly lower disease-free survival (p = 0.029) than those who underwent minimally invasive surgery, however, the overall survival (p = 0.051) was similar between the two groups. Conclusion: Minimally invasive surgery showed better survival outcomes when compared to open surgery in advanced-stage EC patients irrespective of the histologic type.

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease.

OBJECTIVE: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. MATERIALS AND METHODS: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. RESULTS: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). CONCLUSION: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.

Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells.

The present study aimed to analyze the compensatory signaling pathways induced by forkhead domain inhibitor­6 (FDI­6), which is a forkhead box protein M1 (FOXM1) inhibitor, in ovarian cancer cells and evaluate the effectiveness of simultaneous inhibition of FOXM1 and the compensatory signaling pathway in decreasing the survival of ovarian cancer cells. The present study identified the proteins involved in the compensatory mechanism activated by FDI­6 in HeyA8 ovarian cancer cells using western blot analysis and a reverse­phase protein array. In addition, a cell viability assay was performed to determine the effects of FDI­6 and the compensatory signaling pathway on cancer cell viability. All experiments were performed in three­dimensional cell cultures. The present study observed that FDI­6 stimulated the upregulation of N­Ras, phosphoprotein kinase Cδ (p­PKCδ) (S664) and HER3 in HeyA8 cells. Tipifarnib as an N­Ras inhibitor, rottlerin as a p­PKCδ (S664) inhibitor and sapitinib as a HER3 inhibitor were selected. The combination of FDI­6 with tipifarnib attenuated the upregulation of N­Ras induced by FDI­6 and the combination of FDI­6 with sapitinib also attenuated HER3 downstream signaling pathway in HeyA8 cells, as shown by on western blot analysis. Rottlerin downregulated p­PKCδ (S664) by inhibiting the activity of a Src­related tyrosine kinase that transfers a phosphate group to PKCδ. Compared with FDI­6 alone, the addition of tipifarnib or rottlerin to FDI­6 was significantly more effective in reducing the growth of HeyA8 cells. However, the combination of FDI­6 and sapitinib did not induce a significant decrease in survival of HeyA8 cells. In conclusion, the addition of tipifarnib or rottlerin to inhibit N­Ras or p­PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI­6 in HeyA8 cells. These inhibitors increased the efficacy of FDI­6, which inhibits FOXM1, in reducing ovarian cancer cell viability.

Abdominal wall mass suspected of endometriosis: clinical and pathologic features.

OBJECTIVE: To evaluate the clinical and pathological characteristics of lower anterior abdominal wall masses suspicious for endometriosis. METHODS: A retrospective review of 38 patients who underwent surgery for a lower anterior abdominal wall mass suspicious for endometriosis was performed. Those with skin and intraperitoneal masses, lipomas, hernias, and metastatic malignant masses were excluded. Patient age, body mass index, delivery history, dysmenorrhea, and mass size and location were analyzed. RESULTS: Thirty-seven (97.3%) patients had a relevant surgical history, including 35 (92.1%) with a history of cesarean section (C/S). Among the three patients with no history of C/S, 1 underwent total abdominal and another total laparoscopic hysterectomy, and 1 had no previous surgical history. The mean (±standard deviation) size of the abdominal masses was 3.2±1.2 cm. One patient developed a recurrent mass after excision of abdominal wall endometriosis. Trocar site endometrioma was found in one patient following total laparoscopic hysterectomy. According to the final pathology reports, endometriosis was found in 35 (92.1%) of patients. The remaining 3 patients (7.9%) had malignancy: adenocarcinoma, squamous cell carcinoma, and extra-gastrointestinal stromal tumor. Before surgery, only 3 patients (7.9%) underwent fine-needle aspiration biopsy of the masses, which were all postoperatively confirmed to be pathologically benign. CONCLUSION: Although most abdominal wall masses in the present sample were endometriosis occurring at the scar site from a previous operation, 7.9% of patients ultimately exhibited malignancy. Therefore, all patients with suspected anterior wall endometriosis should undergo preoperative biopsy to identify the few that will have an alternative diagnosis.

Diagnostic Accuracy of the Risk of Ovarian Malignancy Algorithm in Clinical Practice at a Single Hospital in Korea.

BACKGROUND: The risk of ovarian malignancy algorithm (ROMA) is used for assessing ovarian cancer risk in women with a pelvic mass. Its diagnostic accuracy is variable. We investigated whether the clinically acceptable minimal sensitivity of >80.0% could be obtained with the suggested cutoff of 7.4%/25.3% for pre/postmenopausal women and with adjusted cutoffs set to a specificity of ≥75.0% or a sensitivity of 95.0%, in a hospital with a lower ovarian cancer (OC) prevalence than previously reported. METHODS: ROMA scores were calculated from measurements of human epididymis protein 4 and cancer antigen 125 in blood specimens from 443 patients with a pelvic mass. The ROMA-based risk group was compared against biopsy (N=309) or clinical follow-up with imaging (N=134) results. The ROMA sensitivity and specificity for predicting epithelial OC (EOC) and borderline ovarian tumor (BOT) were calculated for the suggested and adjusted cutoff values. RESULTS: When targeting BOT and EOC, the prevalence was 7.4% and sensitivity and specificity at the suggested cutoff were 63.6% and 90.7%, respectively. Sensitivity was 81.8% at the 4.65%/13.71% cutoff set to a specificity of 75.0%. When targeting only EOC, the prevalence was 4.1% and sensitivity and specificity at the suggested cutoff were 77.8% and 89.4%, respectively. Sensitivity was 88.9% at the 4.78%/14.35% cutoff set to a specificity of 75.0%. CONCLUSIONS: The sensitivity of ROMA was lower than expected when using the suggested cutoff. When using the adjusted cutoff, its sensitivity reached 80.0%.

Higher parity and risk of metabolic syndrome in Korean postmenopausal women: Korea National Health and Nutrition Examination Survey 2010-2012.

AIM: We sought to examine whether parity is associated with higher incidence of metabolic syndrome in postmenopausal women. METHODS: We conducted a cross-sectional study on 4098 Korean postmenopausal women by using nationally representative data from the Korea National Health and Nutrition Examination Survey 2010-2012. Multivariate logistic regression was performed to evaluate the relationship between parity and metabolic syndrome, with adjustment for potential confounding variables. RESULTS: The rate of metabolic syndrome was significantly higher with increasing number of parity, with dose-response relationship in univariate analysis (P <0.001). In addition, higher parity (≥3 live births) was associated with more prevalence of all components of metabolic syndrome compared with two live births (parity 2 vs 3 vs ≥4: 5.5 vs 12.1 and 14.4%, respectively; P < 0.001). However, after adjusting for demographic, socioeconomic, lifestyle and reproductive factors, we found that only higher parity was significantly associated with metabolic syndrome compared with two live births, and failed to show a dose-dependent relationship (parity 2 vs 3 vs ≥4: odds ratio 1 vs 1.404 vs 1.379, respectively; P = 0.043). We also proved that among the components of metabolic syndrome, only waist circumference had a significant positive relationship with parity in a multivariable adjusted model (parity 2 vs 3 vs ≥4: odds ratio 1 vs 1.559 vs 1.656, respectively; P < 0.001). CONCLUSION: Higher parity was independently associated with a higher risk of metabolic syndrome in postmenopausal women.

Relationship between age at last delivery and age at menopause: The Korea National Health and Nutrition Examination Survey.

OBJECTIVE: We used data from the 2010 to 2012 Korean National Health and Nutrition Examination Surveys to investigate whether the age at menopause is related to age at last delivery. METHODS: This was a cross-sectional study of the data for 714 women who became menopausal within the 3 years preceding the Korean National Health and Nutrition Examination Survey. RESULTS: Smoking, exercise, drink, educational level, and income were adjusted in model 1, and the mean ages at menopause were 50.5±0.3, 51.2±0.2, 51.2±0.3, and 50.2±0.4 years for women with <25, ≥25 and <30, ≥30 and <35, ≥35 years age at last delivery, respectively (P=0.049). Smoking, exercise, drink, educational level, income, age at first delivery, age at last delivery, and gravidity were adjusted in model 2, and the respective mean ages at menopause were 50.5±0.5, 50.7±0.4, 50.3±0.4, and 49.2±0.5 years (P=0.03). In both models, older age at last delivery showed higher age at menopause compared with women with younger age at last delivery. CONCLUSION: Korean women with older age at last delivery were associated with younger age at menopause. Increased number of pregnancies was related to older age at menopause.

Relationship between alcohol consumption and age at menopause: The Korea National Health and Nutrition Examination Survey.

OBJECTIVE: We used data from the 2011-2014 Korean National Health and Nutrition Examination Surveys (KNHANES) to investigate whether the age at menopause is related to alcohol consumption in South Korean women. MATERIALS AND METHODS: This was a cross-sectional study of the data for 940 women who became menopausal within the 3 years preceding the KNHANES. RESULTS: The numbers of nondrinkers, mild to moderate drinkers, and heavy drinkers in this group were 345 (34.7%), 573 (62.2%), and 22 (3%). Body mass index (BMI), smoking, and exercise were adjusted in model 1 and age was additionally adjusted in model 2. The mean ages at menopause were 51.6 ± 0.2, 50.8 ± 0.1, and 50.4 ± 0.5 years (p = 0.0025) in model 1 and 51.7 ± 0.2, 51.1 ± 0.1, and 50.1 ± 0.5 years (p = 0.0018) in model 2 for nondrinkers, mild to moderate drinkers, and heavy drinkers, respectively. BMI, smoking, exercise, educational level, income, duration of menopause, age at menarche, age at first delivery, and gravidity were adjusted in model 3, and the respective mean ages at menopause were 51.3 ± 0.2, 50.7 ± 0.2, and 50.1 ± 0.8 years (p = 0.0402). The population was classified into groups using the Alcohol Use Disorders Identification Test (AUDIT) scores of <5 (n = 778), <10 (n = 108), and ≥10 score (n = 54). The mean ages at menopause according to AUDIT score were 51.3 ± 0.1, 50.5 ± 0.3, and 50.4 ± 0.4 years (p = 0.0222, model 1), 51.4 ± 0.1, 50.8 ± 0.3, and 50.8 ± 0.3 years (p = 0.0261, model 2), and 51.1 ± 0.1, 50.6 ± 0.4, and 49.5 ± 0.6 years (p = 0.0241, model 3) respectively. CONCLUSION: In Korean women, alcohol consumption was associated with younger age at menopause. A higher AUDIT score was also related to younger age at menopause.

Factors associated with participation in cervical cancer screening among young Koreans: a nationwide cross-sectional study.

OBJECTIVES: Despite the possibility of early detection of cervical cancer, participation in screening programmes among young Koreans is low. We sought to identify associations between risk factors and participation in screening for cervical cancer among young Koreans. DESIGN: Nationwide cross-sectional study. SETTING: Republic of Korea. PARTICIPANTS: 3734. MAIN OUTCOME MEASURES: The Korea National Health and Nutrition Examination Survey (KNHANES V: 2010-2012) was used to evaluate factors associated with attendance for cervical cancer screening among women aged 15-39. After excluding those who were previously diagnosed with cervical cancer and those with incomplete responses to questionnaires, a total of 3734 subjects were eligible. Multi-dimensional covariates as potential predictors of cervical cancer screening were adjusted in multiple logistic regression analysis. RESULTS: The participation rate for cervical cancer screening was 46% among women aged 40 or younger. The logistic analyses showed that age, education, total household income, smoking and job status among women aged 15-39 were associated with participation in cervical cancer screening (p<0.05). After age stratification, the associated factors differed by age groups. Moreover, a dose-response between participation in cervical cancer screening and high total household income in the 30-39 age group was seen. CONCLUSIONS: Predictive factors differed among young women (aged 15-29 vs 30-39). Thus, age-specific tailored interventions and policies are needed to increase the participation rate in screening for cervical cancer.

Relationship between delivery history and health-related quality of life in menopausal South Korean women: The Korea National Health and Nutrition Examination Surveys.

OBJECTIVES: The study investigated the association between childbirth history and health-related quality of life (QOL) in menopausal South Korean women. STUDY DESIGN: Cross-sectional analysis of data from the 2010-2012 Korean National Health and Nutrition Examination Surveys (KNHANES) for 4277 menopausal women aged over 50. We used the EuroQol index to measure health-related QOL. MAIN OUTCOME MEASURES: The relationship between delivery history and health-related QOL in menopausal South Korean women was analyzed. RESULTS: After adjustment for age (model 1), women who were younger at their first delivery and who had a greater number of deliveries had a significantly higher risk of problems with mobility, self-care, usual activities and pain or discomfort; the risk of anxiety or depression was not increased. After adjustment for age, BMI, smoking, use of alcohol, exercise, income, education, marital status, metabolic syndrome and stress (model 2), women who were younger at their first delivery and who had a greater number of deliveries had a significantly higher risk of problems with mobility, self-care and pain or discomfort. Age at last delivery was not significantly associated with health-related QOL in either model. CONCLUSIONS: South Korean women who were younger at their first delivery and who had more deliveries appear to be at increased risk of health-related QOL problems after menopause.

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

OBJECTIVE: To identify the proteins involved the compensatory adaptive response to paclitaxel in ovarian cancer cells and to determine whether inhibition of the compensatory adaptive response increases the efficacy of paclitaxel in decreasing the viability of cancer cells. METHODS: We used a reverse-phase protein array and western blot analysis to identify the proteins involved in the compensatory mechanism induced by paclitaxel in HeyA8 and SKOV3 ovarian cancer cells. We used a cell viability assay to examine whether inhibition of the proteins involved in the compensatory adaptive response influenced the effects of paclitaxel on cancer cell viability. All experiments were performed in three-dimensional cell cultures. RESULTS: Paclitaxel induced the upregulation of pS6 (S240/S244) and pS6 (S235/S236) in HeyA8 and SKOV3 cells, and pPRAS40 (T246) in HeyA8 cells. BX795 and CCT128930 were chosen as inhibitors of pS6 (S240/S244), pS6 (S235/S236), and pPRAS40 (T246). BX795 and CCT128930 decreased pS6 (S240/S244) and pS6 (S235/S236) expression in HeyA8 and SKOV3 cells. However, pPRAS40 (T246) expression was inhibited only by BX795 and not by CCT128930 in HeyA8 cells. Compared with paclitaxel alone, addition of BX795 or CCT128930 to paclitaxel was more effective in decreasing the viability of HeyA8 and SKOV3 cells. CONCLUSION: Addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability.