Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib via Regulation of Rad51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate anticancer effects of combination treatment with poly(ADP-ribose) polymerase (PARP) and checkpoint kinase 1 (Chk1) inhibitors in BRCA wild-type ovarian cancer. PARP inhibitors can function as DNA-damaging agents in BRCA wild-type cancer, even if clinical activity is limited. Most epithelial ovarian cancers are characterized by a TP53 mutation causing dysfunction at the G1/S checkpoint, which makes tumor cells highly dependent on Chk1-mediated G/M phase cell-cycle arrest for DNA repair. @*Materials and Methods@#We investigated the anticancer effects of combination treatment with prexasertib (LY2606368), a selective ATP competitive small molecule inhibitor of Chk1 and Chk2, and rucaparib, a PARP inhibitor, in BRCA wild-type ovarian cancer cell lines (OVCAR3 and SKOV3). @*Results@#We found that combined treatment significantly decreased cell viability in all cell lines and induced greater DNA damage and apoptosis than in the control and/or using monotherapies. Moreover, we found that prexasertib significantly inhibited homologous recombination–mediated DNA repair and thus showed a marked anticancer effect in combination treatment with rucaparib. The anticancer mechanism of prexasertib and rucaparib was considered to be caused by an impaired G2/M checkpoint due to prexasertib treatment, which forced mitotic catastrophe in the presence of rucaparib. @*Conclusion@#Our results suggest a novel effective therapeutic strategy for BRCA wild-type epithelial ovarian cancer using a combination of Chk1 and PARP inhibitors.

Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib via Regulation of Rad51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate anticancer effects of combination treatment with poly(ADP-ribose) polymerase (PARP) and checkpoint kinase 1 (Chk1) inhibitors in BRCA wild-type ovarian cancer. PARP inhibitors can function as DNA-damaging agents in BRCA wild-type cancer, even if clinical activity is limited. Most epithelial ovarian cancers are characterized by a TP53 mutation causing dysfunction at the G1/S checkpoint, which makes tumor cells highly dependent on Chk1-mediated G/M phase cell-cycle arrest for DNA repair. @*Materials and Methods@#We investigated the anticancer effects of combination treatment with prexasertib (LY2606368), a selective ATP competitive small molecule inhibitor of Chk1 and Chk2, and rucaparib, a PARP inhibitor, in BRCA wild-type ovarian cancer cell lines (OVCAR3 and SKOV3). @*Results@#We found that combined treatment significantly decreased cell viability in all cell lines and induced greater DNA damage and apoptosis than in the control and/or using monotherapies. Moreover, we found that prexasertib significantly inhibited homologous recombination–mediated DNA repair and thus showed a marked anticancer effect in combination treatment with rucaparib. The anticancer mechanism of prexasertib and rucaparib was considered to be caused by an impaired G2/M checkpoint due to prexasertib treatment, which forced mitotic catastrophe in the presence of rucaparib. @*Conclusion@#Our results suggest a novel effective therapeutic strategy for BRCA wild-type epithelial ovarian cancer using a combination of Chk1 and PARP inhibitors.

Robotic Single-Site Hysterectomy versus Robot-Assisted Multiport Hysterectomy in Benign Gynecologic Diseases: A Retrospective Comparison of Clinical and Surgical Outcomes

OBJECTIVE: The purpose of this study was to compare clinical and surgical outcomes of robotic single-site hysterectomy (RSSH) and robot-assisted multiport hysterectomy (RH) in benign disease. METHODS: We retrospectively reviewed the medical records of 38 women who underwent RSSH (N=12) or RH (N=26) for the treatment of benign uterine disease between June 2015 and November 2017. RESULTS: There were no intergroup differences in parity, comorbidities, and number of previous abdominal surgery. Mean age was older (49.5±5.05 years vs. 44.4±3.54 years, P=0.001) and mean body mass index was higher (27.4±2.47 kg/m2 vs. 25.3±3.12 kg/m2, P=0.045) in RSSH group than RH group. Surgical outcomes, including operative time (165.0 minutes vs. 159.2 minutes, P=0.727), estimated blood loss (115.8±33.15 mL vs. 108.1±56.42 mL, P=0.662), uterus weight (445.9±157.21 g vs. 374.5±197.91 g, P=0.291), postoperative hospital stay (5.4±0.51 days vs. 5.8±1.20 days, P=0.289), postoperative hemoglobin change in day 1 (1.8±0.89 g/dL vs. 1.4±1.53 g/dL, P=0.431) and day 3 (2.1±1.32 g/dL vs. 1.7±1.83 g/dL, P=0.601), and perioperative complications did not significantly differ between two groups. The use of additional analgesics after 6 hours, 24 hours, and 48 hours, and mean NRS score after 6 hours, 24 hours, and 48 hours were not significantly different between two groups. CONCLUSION: RSSH might be an effective and safe alternative to RH, even if in older and/or obese women with large uteri.

Comparison of HE4, CA125, and Risk of Ovarian Malignancy Algorithm in the Prediction of Ovarian Cancer in Korean Women

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.

Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance

OBJECTIVE: Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. METHODS: A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of HPV test for high-grade cervical intraepithelial neoplasia (CIN2+) was evaluated. RESULTS: Median age was 44 years (range, 17 to 75 years). ASCUS was more frequently observed in older patients while LSIL was more common in younger patients (P=0.002). CIN2+ was found in 11.3% (32/284) of the ASCUS patients and 12.9% (20/155) of patients with LSIL. Older patients with ASCUS showed lower HPV infection rates (P=0.025), but not LSIL (P=0.114). However, the prevalence of CIN2+ was similar between the age groups with ASCUS or LSIL. In patients with ASCUS, the false negative rate of HPV test for CIN2+ was 6.2%. The false negative rate of the HPV test became higher with increasing of the age after the age of 50 (P=0.034). CONCLUSION: Our findings suggest that false negative rate of the HPV test for CIN2+ in ASCUS patients older than 50 years might become higher with increasing of the age. Negative HPV results in patients of the age >50 years with ASCUS should be carefully interpreted.

Superficial cervicovaginal myofibroblastoma: a report of two cases and literature review / 대한산부인과내시경학회지

Superficial cervicovaginal myofibroblastoma (SCVM) is extremely rare mesenchymal tumor arising low genital tract. SCVM is characterized by asymptomatic polypoid or nodular mass within the lamina propria. It is difficult to distinguish SCVM from other genital mesenchymal tumors because of similar morphologic features, however SCVM has distinctive histological and immunohistochemical profiles. SCVM is considered benign tumor which can be treated with simple excision and shows rare recurrence. We experienced two cases of SCVM which was treated with simple excision. We present these cases, along with a review of the relevant literatures.

Evaluation of length, volume and gray-scale histogram of the cervix as predictors of successful induction / 대한산부인과학회지

OBJECTIVE: The aim of this study was to evaluate whether the Bishop score, length, volume and gray-scale histogram of the cervix has a predictive value of assessing the rate of success in trial of induction. METHODS: Forty-one nulliparous patients with its Bishop score six or less were enrolled for this prospective study. All were on prostaglandin E2 (PGE2, Propess(R); Controlled Therapeutics Ltd) pessary. Three-dimensional transvaginal ultrasound scans of the cervix were performed on the ACCUVIX XQ (Medison) to measure length, volume, and gray-scale histogram. Bishop score was determined by digital examination. The successful induction was defined as the ability to achieve the active phase of labor corresponding to a cervical dilatation of > or =4 cm within 12 hours of removing the PGE2 pessary. The receiver operating characteristics (ROC) curves were also used to estimate an optimal cutoff point for the Bishop score, length, volume, and gray-scale histogram of the cervix. Logistic regression analysis was used for statistical analyses. RESULTS: The overall successful rate of labor induction was 73.2% (30/41). Multiple logistic regression analyses demonstrated that the value of anterior lip histogram was significantly associated with the successful labor induction. ROC curve for anterior lip histogram value in predicting success of induction indicated a significant relationship with successful induction. The best cutoff value was 69.4. CONCLUSION: The value of anterior lip histogram associates significantly with the prediction of successful induction in nulliparous women. But, Bishop score and other sonographic measurement of cervical length, volume, and posterior lip histogram have no predictive values for successful induction.

Changes of antioxidant levels in the uterine venous plasma amniotic fluid, and chorioamnion after maternal supplementation with vitamin C and vitamin E / 대한주산의학회잡지

PURPOSE:To investigate the change in the antioxidant vitamin levels in maternal uterine venous plasma (MUVP), amniotic fluid (AF), and chorioamnion after vitamin C and E supplementation during pregnancy. METHODS:Thirty pregnant women who were scheduled for elective cesarean section between 37 and 39 gestational weeks were randomized in this study. Fifteen women were given a daily oral dose of vitamin C 1,000 mg and vitamin E 400 IU from 33~34 gestational weeks to delivery. The other fifteen women were not given, as a control group. Maternal uterine venous blood, AF, and chorioamnion were obtained after cesarean section. Lipid peroxides and oxygen-radical absorbance capacity value were measured by thiobarbituric acid reaction and Cao's method respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. The tissue sections of chorioamnion were stained with hematoxylin-eosin and Masson-trichrome stain, and immunohistochemical stain for collagen type IV was also performed. RESULTS:The lipid peroxide levels in MUVP of the study group were significantly lower than those of the control group but in contrast, ORAC (Oxygen-radical absorbance capacity) values were lower in the control group. The alpha-tocopherol levels in MUVP, AF, and chorioamnion study group were significantly higher than those of the control group. Amniotic membrane and subepithelial stromal tissue in the study group were thicker than those in the control group. And subchorionic type IV collagen of placenta tissue in the study group was more stained than that of the control group. CONCLUSION:Maternal vitamin C and E supplementation may be beneficial in the prevention of diseases caused by oxidative stress such as preeclampsia and PROM and in increasing fibrin and type IV collagen in chorioamnion.

Effect of vitamin C and E on the lipid peroxide, antioxidant ability, and antioxidant vitamin levels in maternal and umbilical venous plasma / 대한산부인과학회지

OBJECTIVE: This controlled trial investigated the effect of supplementation with vitamins C and E on the lipid peroxide, antioxidant ability, and antioxidant vitamin levels in full term maternal and umbilical venous plasma. METHODS: Forty pregnant women were randomized in this study. They were nulliparous or multiparous women with history of preeclampsia or preterm premature rupture of membranes (PPROM). Twenty women were given vitamin C (1,000 mg/day) and vitamin E (400 IU/day) from 15~20 gestational weeks to delivery. The others were not given, as a control group. Maternal venous blood was obtained before vitamin supplementation and just before delivery. Umbilical venous blood was obtained after delivery. Lipid peroxide level and oxygen-radical absorbance capacity (ORAC) were measured by thiobarbituric acid reaction and Cao's method, respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. Results: Supplementation with vitamins C and E was associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in maternal venous plasma. And it was also associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in umbilical venous plasma. CONCLUSION: Supplementation with vitamins C and E may be beneficial in the prevention of oxidant-antioxidant imbalance origin diseases such as preeclampsia, PPROM. And it also may affect antioxidant ability of the fetus.

Successful full-term delivery after abdominal radical trachelectomy and concurrent cervicoisthmic cerclage for early stage cervical cancer: Two cases / 대한산부인과학회지

Since the screening tool was introduced, the incidence and mortality of cervical carcinoma has decreased. However, the incidence of early stage cervical cancer is increasing in young women who want to preserve their fertility. The risk of preterm delivery after trachelectomy is high and remains problematic. Herein we report two patients who had successful full-term delivery after abdominal radical trachelectomy and concurrent cervicoisthmic cerclage for early stage cervical cancer.

A case of ureterouterine fistula as a complication of cesarean section / 대한산부인과학회지

Ureteral injury is usually iatrogenic in origin, in particular as a result of laparoscopic or gynecological surgery. Ureterouterine fistula constitute a rare subset of iatrogenic genitourinary fistulas. The most common presentation of ureterouterine fistula is in women who have had a cesarean section. The management options include conservative therapy (spontaneous healing), endourologic (stented repair) or open surgical operation (ureteroneocystostomy or ureteroureterostomy). Herein, we report on a case of ureterouterine fistula in a 33-year-old woman who underwent a cesarean section. The 17th day after the operation, she complained watery vaginal discharge. Clinical and urographic assessments revealed an iatrogenic ureterouterine fistula and an ureteroneocystostomy was performed after 3 months.

Current concepts of drugs use during pregnancy / 대한산부인과학회지

More than 90% of pregnant women take drugs or use social drugs (such as tobacco and alcohol) or illicit drugs at some time during pregnancy. In general, drugs, unless absolutely necessary, should not be used during pregnancy because many can harm the fetus. The wrong informations of the drugs make an unnecessary termination. Sometimes drugs are essential for the health of the pregnant woman and the fetus. In such cases, appropriate and correct informations of drugs must be taken by specialist. Pregnancy women should talk with her doctors about the risks and benefits of taking the drugs. This article suggests general informations about using drugs in pregnancy.

Changes in lipid peroxidation and protein oxidation by antibiotic therapy in the maternal venous plasma of preterm premature rupture of membranes / 대한산부인과학회지

OBJECTIVE: To investigate and compare the amount of the lipid peroxidation and the protein carbonyls formation in maternal venous plasma of preterm premature rupture of membranes (PPROM) during antibiotics administration. METHODS: PPROM were selected between 25 and 32 weeks of gestation. Eighteen patients (group 1) were treated with amoxicillin and erythromycin for 7 day period, 18 patients (group 2) were treated with 3rd generation cephalosporin (cefodizime, cefditoren) and erythromycin for the same period. Maternal blood were obtained from the two groups before and after the antibiotics administration, day 3 and day 7. Lipid peroxidation levels and protein carbonyl contents were measured by thiobarbituric acid reaction and 2,4-dinitrophenyl hydrazine method. Other 18 women with normal pregnancy between 25 and 32 weeks of gestation of venous blood were checked same things in vitro. Interleukin (IL) -6 was measured by enzyme-linked immunosorbent assay. RESULTS: 1. The lipid peroxidation levels and protein carbonyls formation in the maternal venous plasma of PPROM was significantly higher than that of normal pregnancy (lipid peroxidation levels; 4.77+/-.36 vs 7.11+/-.41 nmol/mg protein, P<001, protein carbonyls formation; 3.55+/-.22 vs 5.69+/-.30 nmol/mg protein, P<001). 2. There were no significant differences in the lipid peroxidation levels and protein carbonyls formation of the maternal venous plasma with PPROM mixed and incubated by amoxicillin, cefodizime, cefditoren, and erythromycin (in vitro). 3. There were no significant differences in the lipid peroxidation levels and protein carbonyls formation of the venous plasma of group 1 between before and after antibiotics administration, day 3 and day 7. 4. There were no significant differences in the lipid peroxide levels of the venous plasma of group 2 between before and after antibiotics administration, day 3 and day 7. 5. The protein carbonyls formation in the venous plasma of group 2 was significantly decreased at day 3 and day 7 after antibiotics administration than that of before (6.04+/-.44 and 5.53+/-.37 vs. 7.04+/-.51 nmol/mg protein, P<005). 6. The levels of IL-6 in the venous plasma of group 2 was significantly decreased at day 7 after antibiotics administration than that of before (7.50+/-.35 vs. 3.13+/-.37 pg/mL, P<005). CONCLUSION: In the maternal venous plasma of PPROM, the lipid peroxidation levels and protein carbonyls formation were increased. The formation of protein carbonyls and IL-6 in the maternal blood of PPROM was decreased by combined treatment of 3rd generation cephalosporin and erythromycin. The results suggest that reactive oxygen species formation by inflammatory reaction is suppressed by the 3rd generation cephalosporins and erythromycin combined treatment.

A case of acute pulmonary edema with peripartum cardiomyopathy in severe preeclampsia / 대한산부인과학회지

Women with severe preeclampsia or eclampsia who develop pulmonary edema most often do so postpartum and some of these women have cardiac failure. Peripartum cardiomyopathy is defined as a cardiac failure occurring in the latter part of pregnancy or in the peripartum, without obvious cause and prior evidence of heart disease. It is very rare but the mortality rate is as high as 10~50%. Here, we describe a case of a woman who has undergone emergency Cesarean section due to complicated severe preeclampsia with acute pulmonary edema and peripartum cardiomyopathy at 33+1 weeks of gestation.