The risk factors for premalignant and malignant endometrial polyps in premenopausal and postmenopausal women and trends over the past decade: A retrospective study in a single center, South Korea.

OBJECTIVES: To assess the prevalence and risk factors for premalignancy and malignancy in endometrial polyps and to evaluate trends over the past decade. STUDY DESIGN: This was a retrospective study of patients who underwent hysteroscopic polypectomy at Inha University Hospital, South Korea between January 2013 and June 2023. The demographic and clinical characteristics of the patients reviewed to identify risk factors for premalignancy and malignancy in endometrial polyps included the following: age, parity, body mass index, menopausal status, abnormal uterine bleeding symptoms, diabetes mellitus, hypertension, polycystic ovarian syndrome, use of menopausal hormonal therapy or oral contraceptives, tamoxifen treatment in patients with breast cancer, and the number of polyps. RESULTS: In total, 725 patients were enrolled, among whom 52 (7.2 %) had premalignant and malignant lesions. In logistic regression analysis, menopause (OR: 8.37, 95 % CI [3.33-21.04]), abnormal uterine bleeding (OR: 7.42, 95 % CI [2.13-25.86]), obesity (OR: 3.22, 95 % CI [1.53-6.77]), multiple polyps (OR: 2.86, 95 % CI [1.39-5.88]) and nulliparity (OR: 2.64, 95 % CI [1.13-6.19]) were significantly associated with premalignancy and malignancy in polyps. Annual trends during the study period showed an increase in the number of patients with three of the five risk factors (obesity, multiple polyps, and nulliparity) and an increase in the prevalence of premalignancy and malignancy in polyps. CONCLUSIONS: Menopause, abnormal uterine bleeding, obesity, multiple polyps, and nulliparity increase the risk of premalignancy and malignancy in endometrial polyps. The prevalence of premalignant and malignant polyps has been increasing over the past decade. The risk factors that have contributed to this trend were obesity, nulliparity, and multiple polyps.

Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

Postoperative Hormone Replacement Therapy and Survival in Women with Ovarian Cancer.

The effect of postoperative hormone replacement therapy (HRT) on survival in women with ovarian cancer remains unclear. This study aimed to investigate the impact of postoperative HRT on survival in women with ovarian cancer using the nationwide cohort study. Women aged ≤60 and diagnosed with ovarian cancer that received primary surgery were followed-up for 5.6 ± 2.9 years. Mean ages of women administered HRT (the HRT group; n = 263) or not administered HRT (the control group; n = 1521) were 41.5 ± 8.5 and 41.0 ± 11.4 years, respectively. After adjustment for covariables, OS was significantly greater in the HRT group (HR 0.618; 95% CI 0.414−0.922; p = 0.018). Kaplan−Meier curve analysis showed OS was significantly higher in the HRT group (85.3% vs. 76.6%; p = 0.016). The ratio of women with HRT to women without HRT increased significantly with time (restricted mean survival times for OS, p < 0.001). In addition, OS was significantly greater for those that received HRT for >5 years than for those that received HRT for ≤0.5 years (HR 0.234; 95% CI 0.059−0.936; p = 0.040). Postoperative HRT improved survival among women with ovarian cancer. The impact of HRT on survival increased with time and treatment duration.

Bevacizumab versus PARP-inhibitors in women with newly diagnosed ovarian cancer: a network meta-analysis.

BACKGROUND: In women with newly diagnosed ovarian cancer, bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) exhibit improved progression-free survival (PFS) when administered concurrent with chemotherapy and/or maintenance therapy, but no study has directly compared their effects. Therefore, this study aimed to compare the efficacy and safety of bevacizumab and PARPi in women with newly diagnosed ovarian cancer using a network meta-analysis. METHODS: PubMed, Medline, and Embase databases were searched, and five randomized trials assessing PFS in women with newly diagnosed ovarian cancer treated with either bevacizumab, PARPi, or placebo or no additional agent (controls) were identified. PFS was compared in the overall population with ovarian cancer, women with a BRCA1/2 mutation (BRCAm) and women with homologous-recombination deficiency (HRD). Adverse events (grade ≥ 3) were compared in all populations of the included studies. RESULTS: PARPi improved PFS significantly more than bevacizumab in women with a BRCAm (HR 0.47; 95% CI 0.36-0.60) and with HRD (HR 0.66; 95% CI 0.50-0.87). However, in the overall population with ovarian cancer, no significant difference in PFS was observed between women treated with PARPi and those treated with bevacizumab. PARPi exhibited the highest surface under the cumulative ranking probabilities value as the most effective treatment for PFS (PARPi vs. bevacizumab: 98% vs. 52% in the overall population with ovarian cancer; 100% vs. 50% in women with BRCAm; 100% vs. 50% in women with HRD). For adverse events, the risk of all treatments was similar. However, PARPi had a higher adverse risk than the control group (relative risk 2.14; 95% CI 1.40-3.26). CONCLUSIONS: In women with newly diagnosed ovarian cancer, PARPi might be more effective in terms of PFS compared to bevacizumab. The risk of serious adverse events was similar for PARPi and bevacizumab.

Incidence and risk of venous thromboembolism according to primary treatment type in women with endometrial cancer: a population-based study.

BACKGROUND: Current prophylaxes and treatments for venous thromboembolism (VTE) in women with gynecologic cancer are mainly guided by studies on solid cancers because studies in gynecologic cancer did not provide sufficient data. Large-scale studies evaluating the incidence and risk of VTE according to therapeutic modality may guide prophylaxis and treatment of VTE in gynecologic cancer. This study was performed to determine the incidence and risk of VTE according to primary treatment type in Korean women with endometrial cancer. METHODS: We selected 26,256 women newly diagnosed with endometrial cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service database. During the total follow-up period and first six months after primary treatments initiation, the incidence and risk of VTE were evaluated according to primary treatment type, that is, no treatment, surgery, radiotherapy, chemotherapy, or hormone therapy. RESULTS: VTE occurred in 136 per 10,000 women during the total follow-up period and in 54 per 10,000 women during the first six months with the highest frequency in women that underwent chemotherapy. During the first year, the monthly incidence of VTE decreased with time among women that underwent no treatment, surgery, or hormone therapy and remained unchanged in those that received radiotherapy or chemotherapy. Compared with women that received no treatment, VTE risk, especially of PE significantly increased in women that underwent chemotherapy (VTE: hazard ratio (HR), 2.334; 95% CI, 1.38-3.949; P = 0.002) (PE: HR, 2.742; 95% CI, 1.424-5.278; P = 0.003) or hormone therapy (VTE: HR, 2.073; 95% CI, 1.356-3.17; P = 0.001) (PE: HR, 2.086; 95% CI, 1.19-3.657; P = 0.01) during the total follow-up period and women that underwent only chemotherapy during the first six months (VTE: HR, 2.532; 95% CI, 1.291-4.966; P = 0.007) (PE: HR, 3.366; 95% CI, 1.496-7.576; P = 0.003). CONCLUSIONS: In this cohort study, the incidence and risk of VTE were highest in women with endometrial cancer that underwent chemotherapy as a primary treatment. Notably, the incidence of VTE decreased over time in women that received no treatment, surgery, or hormone therapy. This study can help guide therapies for prophylaxis and treatment of VTE in women with endometrial cancer.

Impact of Progesterone on Molecular Mechanisms of Preterm Premature Rupture of Membranes.

The role and mechanisms of progesterone in preterm premature rupture of membranes (PPROM) remains unclear. This study aims to investigate the molecular mechanisms of action of progesterone in pre-labor full-term fetal amniotic membrane cells with and without stimulation by microbial, pro-inflammatory, or thrombogenic agents. Fetal amniotic membranes were collected from 30 women with a normal singleton pregnancy undergoing elective cesarean section at term prior to the onset of labor. The human amniotic epithelial cells isolated were pretreated with and without medroxyprogesterone acetate for 24 h. Then, cells were treated with and without TLR/NLR agonists, pro-inflammatory cytokines, or thrombin for 48 h. Semi-quantitative RT-PCR, Western blot, and caspase-3 activity measurement were performed. Progesterone stimulation decreased the expression of TLR2, TLR5, and Nod2 genes (alone and/or in combination with TLR/NLR agonists) and decreased the expression of IL-1ß and IL-8 genes increased by stimulation with specific agonists for TLR2, TLR4, TLR5, Nod1, and Nod2. Moreover, progesterone decreased thrombin-induced IL-8 gene expression. Progesterone also decreased expression of Bax and Bid proteins (pro-apoptotic factors) increased by stimulation with pro-inflammatory cytokines (TNF-α, NGAL, IL-18, and IL-1ß) and thrombin. Progesterone stimulation alone as well as co-stimulation with TNF-α, NGAL, IL-18, IL-1ß, or thrombin with progesterone either increased, decreased, or did not change the expression of Bcl-2, Bcl-XL, or XIAP genes (anti-apoptotic factors). These data suggest progesterone plays protective roles against PPROM through anti-microbial, anti-inflammatory, and anti-thrombogenic actions on human-term fetal amniotic membrane cells. Progesterone alters pro-inflammatory cytokine- and thrombin-induced apoptosis by controlling the expression of pro-apoptotic and anti-apoptotic factors.

Incidence and risk factors of VTE in patients with cervical cancer using the Korean national health insurance data.

This study investigated incidence and risk factors for venous thromboembolism (VTE) in patients with cervical cancer. We selected 49,514 patients newly diagnosed with cervical cancer from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and first 6 months after initiation of primary treatments, incidence of VTE, and association of risk factors with VTE occurrence were evaluated according to primary treatments or no treatment, surgery, radiotherapy, and chemotherapy. VTE occurred in 1.15% of patients with cervical cancer. Regardless of the period after initiation of primary treatments, and of VTE, the incidence of thromboembolism was highest in chemotherapy. During the first 12 months, monthly incidence of VTE was highest in chemotherapy and decreased with time in all primary treatments. Compared with no treatment, VTE risk significantly increased for all primary treatments (surgery: HR 1.492; 95% CI 1.186-1.877) (radiotherapy: HR 2.275; 95% CI 1.813-2.855) (chemotherapy: HR 4.378; 95% CI 3.095-6.193) and for chemotherapy during the first 6 months (HR 3.394; 95% CI 2.062-5.588). In this cohort study, incidence and risk of VTE in patients with cervical cancer were the highest when chemotherapy was the primary cancer treatment, and incidence of VTE decreased with time.

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. METHODS: We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. RESULTS: The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08-1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401-0.775; P<0.001) and radiotherapy (HR 0.289; 95% CI, 0.119-0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86-12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757-4.485; P<0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37-13.022; P = 0.012) during the first six months. CONCLUSIONS: In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

Risk factors of progression to endometrial cancer in women with endometrial hyperplasia: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate risk factors of progression to endometrial cancer (EC) in women with non-atypical and atypical endometrial hyperplasia (EH). METHODS: The data of 62,333 women with EH diagnostic codes from 2007 to 2018 were sourced from the Korean Health Insurance Review and Assessment Service databases. The data from 11,525 women with non-atypical EH and 2,219 women with atypical EH who met the selection criteria were extracted for analysis. RESULTS: Risk of EC in women with EH decreased in 40-49 year olds compared to other ages (non-atypical EH: [≤39 vs. 40-49 years] HR, 0.557; 95% CI, 0.439-0.708; P<0.001; [≤39 vs. ≥50 years] P = 0.739; atypical EH: [≤39 vs. 40-49 years] HR, 0.391; 95% CI, 0.229-0.670; P = 0.001; [≤39 vs. ≥50 years] P = 0.712). Risk of EC increased with increase in number of follow-up biopsies in women with non-atypical EH (1 biopsy: HR, 1.835; 95% CI, 1.282-2.629; P = 0.001; ≥2 biopsies: HR, 3.644; 95% CI, 2.585-5.317; P<0.001) and in women receiving ≥2 follow-up biopsies with atypical EH (HR, 3.827; 95% CI, 1.924-7.612; P = 0.001). Time of progression to EC decreased in women ≥50 years old with non-atypical EH compared to other ages (P = 0.004) and showed no differences among ages in women with atypical EH (P = 0.576). Progestational agents were a protective factor for EC in women with non-atypical EH (HR, 0.703; 95% CI, 0.565-0.876; P = 0.002). CONCLUSIONS: In this claim data analysis, women ≤39 and ≥50 years old with EH were at a high risk for progression to EC, and repeat follow-up biopsy after a diagnosis of EH increased detection of EC. Progestational agents were an effective modality to prevent EC in women with non-atypical EH.

Decreased expression of progesterone receptor membrane component 1 in fetal membranes with chorioamnionitis among women with preterm birth.

PURPOSE: Progesterone receptor membrane component 1 (PGRMC1) have anti-inflammatory and anti-apoptotic properties. This study aimed to determine the expression of PGRMC1 in fetal membranes among women with preterm labor (PTL), preterm premature rupture of membranes (PPROM), and acute histologic chorioamnionitis (HCA) during preterm birth. METHODS: Full thickness fetal membranes were obtained from women with gestational age-matched (32-34 weeks of gestational age), and categorized as PTL without HCA (PTL, n = 10), PPROM without HCA (PPROM, n = 10), PPROM with HCA (HCA, n = 10), and term without labor and HCA (term birth (TB), n = 9). The expression of PGRMC1 was assessed using western blot and Immunohistochemistry (IHC). As CD14 is a component of the innate immune system during inflammation, CD14 was used as inflammatory indicator. Nonparametric statistics were used for analysis. RESULTS: PGRMC1 expression for all of preterm birth was lower than in TB (P = 0.01). In HCA, PGRMC1 expression was significantly decreased compared to that in PTL and PPROM (P = 0.006. P = 0.001, respectively). PGRMC1 expression in PPROM was higher than that in PTL (P = 0.002). There was a negative correlation between PGRMC1 and CD 14/ß-actin ratio (r = - 0.518; P = 0.002). IHC showed that PGRMC1 was predominant in the cytoplasm of cells, these results were consistent with those of the western blot analysis. CONCLUSION: Preterm birth with PTL, PPROM, and especially HCA is associated with a decreased PGRMC1 in fetal membranes and inversely associated with increased CD 14.

Tuberculous peritonitis in the first trimester of pregnancy.

Tuberculous peritonitis in pregnancy is a rare form of extrapulmonary tuberculosis that is not easily diagnosed. The clinical presentations of tuberculous peritonitis are usually non-specific and mimic those of other diseases, such as ovarian malignancy or chronic liver disease, and this non-specificity can cause diagnostic delays and complications. The authors report the case of a 31-year-old primigravida woman who presented with uncontrolled fever, dyspnea, elevated liver enzymes, and mild abdominal distension at 13+2 weeks of gestation. At 14+2 weeks, a therapeutic abortion was conducted and tuberculous peritonitis was confirmed by laparoscopic excisional biopsy of peritoneal nodules and histopathologic examination. The patient recovered on antituberculosis therapy and abdomen and chest follow up radiographic findings have confirmed improvement.

Is a cause of postpartum hemorrhage of using of tocolytic agents in preterm delivery?

OBJECTIVE: Tocolytic agents are used to inhibit uterine contraction in preterm. The authors undertook this study to determine whether using of tocolytic agents before delivery is associated with increase postpartum hemorrhage in preterm delivered women. METHOD: 296 singleton pregnancies delivered preterm from 24 + 1 to 37 + 0 weeks gestation were retrospectively reviewed. Hemoglobin (HB) and hematocrit (HCT) levels were checked before and after delivery to access postpartum blood loss. Multivariate logistic regression analysis was performed to determine whether delivery within the half-lives of tocolytic agents was associated with decreased HB and HCT levels. RESULTS: After adjusting for maternal age, parity, gestational age at delivery, birth weight, delivery method, and induction of labor, postpartum HB and HCT levels of those delivered within half-lives of tocolytic agents were found to be significantly diminished (HB: OR 3.306, 1.308-8.356 95% CI, p = 0.011; HCT: OR 2.692, 1.077-6.726 95% CI, p = 0.034). In addition, blood transfusion rates were elevated for deliveries made within the half-lives of tocolytic agents, (p = 0.006). CONCLUSIONS: Delivery within half-lives of tocolytic agents was found to be associated with low HB and HCT levels after delivery and higher blood transfusion rates in preterm delivered women.

Uterine prolapse in a primigravid woman.

Uterine prolapse during pregnancy is an uncommon condition. It can cause preterm labor, spontaneous abortion, fetal demise, maternal urinary complication, maternal sepsis and death. We report the case of uterine prolapse in a 32-year-old healthy primigravid woman. She had no risk factors associated with uterine prolapse. She was conservatively treated, resulting in a successful vaginal delivery. This report is a very rare case of uterine prolapse in a young healthy primigravid woman, resulting in a successful vaginal delivery.

A live birth after spontaneous complete chorioamniotic membrane separation associated with uterine scar.

Spontaneous complete chorioamniotic membrane separation (CMS) without invasive fetal procedure is extremely rare and associated with adverse perinatal outcomes. A woman with complete CMS which was detected at the 21 weeks' gestation. She did not take any fetal invasive procedures before the diagnosis. At 27 weeks' gestation, an emergency Caesarean section was performed because of fetal distress. The defect of the uterine muscle was detected on the fundus. The baby has grown well without any morbidity. This is the first reported case of complete CMS relative to uterine scar. And we suggest that the pregnancy can be maintained successfully if there is no fetal abnormality when complete CMS is detected on ultrasound.

Abdominal wall metastasis of uterine papillary serous carcinoma in a post-menopausal woman: a case report.

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and poor prognosis. We report a case of a 58-year-old post-menopausal woman with an abdominal wall metastasis in stage IA UPSC. After surgical staging, she did not receive additional adjuvant therapy. An egg sized palpable mass developed in the right lower abdomen after 8 months. Both Abdominopelvic computed tomography (CT) and positron emission tomography (PET)-CT revealed a metastatic lesion in the abdominal wall. Hence, surgical excision was performed. The pathological findings showed metastatic UPSC with clear resection margin. After the diagnosis of UPSC metastasis in the abdominal wall, she received chemotherapy utilizing paclitaxel and carboplatin. After 3 years, no evidence of recurrence was found. Therefore, we suggest that even when UPSC is confined to the endometrium without lymph node metastasis and without lymphovascular invasion, chemotherapy should be considered as a postoperative adjuvant therapy.

Incidental diagnosis of vaginal schwannoma in a patient with thigh pain.

Schwannoma commonly arises from Schwann cells of the neural sheath, and is rare in the groin region. Here, we describe a vaginal schwannoma incidentally detected by magnetic resonance imaging (MRI) in a patient with thigh pain. A 43-year-old woman presented with thigh pain with burning and tingling sensations in the medial aspect of her left thigh. MRI revealed a mass lesion of heterogeneous intensity 5.2 × 5.7 cm in the left vaginal wall. The mass was resected and histology revealed schwannoma.

Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells.

Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

Quantitative determination of enzalutamide, an anti-prostate cancer drug, in rat plasma using liquid chromatography-tandem mass spectrometry, and its application to a pharmacokinetic study.

This report details a method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) that allows one to determine the concentration of an atypical anticancer drug, enzalutamide, in rat plasma. Specifically, this method involves the addition of an acetonitrile and bicalutamide (internal standard) solution to plasma samples. Following centrifugation of this mixture, an aliquot of the supernatant was directly injected into the LC-MS/MS system. Separation was achieved using a column packed with octadecylsilica (5 µm, 2.1 × 50 mm) with 10 mM ammonium acetate in acetonitrile as the mobile phase; detection was accomplished using MS/MS by multiple-reaction monitoring via an electrospray ionization source. This method demonstrated a linear standard curve (r = 0.997) over a concentration range of 0.001-1 µg/mL, as well as an intra- and inter-assay precision of 2.7 and 5.1%, respectively, and an accuracy range from 100.8 to 105.6%. The lower limit of quantification was 1.0 ng/mL in 50 µL of rat plasma sample. We also demonstrated that this analytical method could be successfully applied to the pharmacokinetic study of enzalutamide in rats.

Liver recurrence in early endometrial cancer with focal myometrial invasion.

Endometrial cancer is the most common malignancy of the female genital tract. The cancer spreads by direct extension, transtubal dissemination, lymphatic dissemination, and/or by hematogenous spread, usually results in lung metastasis, but may less commonly involve liver, brain, and bone. Here, we describe a patient with stage IA endometrial cancer who developed liver recurrence 17 months after surgery.

Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach.

Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at http://pombe.kaist.ac.kr/compendium.