Synthetic Steroid Hormones Regulated Cell Proliferation Through MicroRNA-34a-5p in Human Ovarian Endometrioma.

Endometriosis is the hormone-dependent product of endometrial tissue found outside the uterus. Recently, micro-RNAs (miRNAs) were shown to play a role in endometriotic lesion development. However, the mechanism of steroid hormones responsible for miRNA remains obscure. In the present study, we assayed for the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate [MPA]) on miRNAs in endometriosis. We used a global miRNA expression profile microarray to evaluate miRNA expression in endometrial mesenchymal stem cells (EN-MSCs) of ovarian endometrioma following treatment with 1 µM danazol, progesterone, or MPA. Furthermore, we selected candidate miRNAs whose expression changed more than fivefold and compared the effects of danazol, progesterone, and MPA treatments and also compared those results with controls in EN-MSCs. Among those with a fivefold change, we found 13 ectopically upregulated miRNAs in EN-MSCs. To understand the function of these 13 miRNAs, we subjected their sequences to Ingenuity Pathway Analysis. According to both the etiology and pathogenesis of endometriosis, we found that miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Steroid hormone treatment elevated the levels of miR-199a-5p and miR-34a-5p. An inhibitor of miR-34a-5p also reduced the synthetic steroid hormones effects on cell proliferation. In vivo data revealed that miRNA levels in endometriotic lesions correlated with findings following in vitro synthetic hormone treatment. Our data show the effects of synthetic steroid hormones on miRNA regulation. These findings contribute to our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment.

miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis.

It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, we found that the tumour suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic endometrial mesenchymal stem cells. Up-regulation of miR-199a-5p suppressed cell proliferation, motility and angiogenesis of these ectopic stem cells by targeting the 3' untranslated region of VEGFA. Furthermore, we established an animal model of endometriosis and found that miR-199a-5p could decrease the size of endometriotic lesions in vivo. Taken together, this newly identified miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility and angiogenesis, and may facilitate the development of potential therapeutics against endometriosis.

Pituitary apoplexy induced by Gonadotropin-releasing hormone agonists for treating prostate cancer-report of first Asian case.

We present the first Asian case of a 77-year-old man who developed pituitary apoplexy (PA) soon after gonadotropin-releasing hormone agonist (GnRHa) (leuprorelin) injection to treat prostate cancer. Headache, ophthalmoplegia, visual field deficit, nausea, and vomiting are the typical characteristics of pituitary apoplexy. Though the occurrence rate is rare, the consequence of this condition can vary from mild symptoms such as headache to life-threatening scenarios like conscious change. Magnetic resonance imaging is the best imaging modality to detect PA and sublabial trans-sphenoid pituitary tumor removal can resolve most of PA symptoms and is so far the best solution in consensus. We also review 11 previous reported cases receiving GnRHa for androgen deprivation therapy of prostate cancer, and hope to alert clinicians to use GnRHa with caution.

Pelvic inflammatory disease is associated with ovarian cancer development in women with endometriosis: A cohort study in Taiwan.

OBJECTIVE: Endometriosis and pelvic inflammatory disease are considered to be risk factors for ovarian cancer, as dysbiosis probably contributes to ovarian cancer development via chronic inflammation and immune response alteration. Therefore, we hypothesized that pelvic inflammatory disease predisposes to ovarian cancer development in women with endometriosis. METHODS: We selected patients who were diagnosed with endometriosis or pelvic inflammatory disease between January 1, 2000 and December 31, 2015, in a 2 million longitudinal health and welfare database in Taiwan with cancer and death registries. Patients were divided into five groups: (1) those with endometriosis, (2) those with pelvic inflammatory disease, (3) those with endometriosis diagnosed before pelvic inflammatory disease, (4) those with pelvic inflammatory disease diagnosed before endometriosis, and (5) healthy women. Propensity score matching with inverse probability of treatment weighting was used to adjust for covariates across the study groups. RESULTS: The risk of ovarian cancer was significantly higher in women with endometriosis and subsequent pelvic inflammatory disease than in those with endometriosis alone (hazard ratio 8.07; 95% confidence interval 4.53-14.37; P < 0.001). The same result was found for ovarian cancer incidence per 1000 person-years. CONCLUSION: Our data show that pelvic inflammatory disease is associated with cancer development in women with pre-existing endometriosis.

Changes in sexual function and vaginal topography using transperineal ultrasound after vaginal laser treatment for women with stress urinary incontinence.

We aim to assess the changes in sexual function and vaginal topography using 3-D transperineal ultrasound in stress-incontinent women treated with Er:YAG vaginal laser. Two hundred and twenty women with stress urinary incontinence (SUI) treated with Er:YAG laser were recruited. Assessment before and 6 months after the treatment included vaginal topography using 3-D transperineal ultrasound and sexual function using female sexual function index questionnaire (FSFI). A total of 50 women with complete data showed that the symptomatic improvement was noted in 37 (74%) women. After Er:YAG vaginal laser treatment, significantly decreased width and cross-sectional area in proximal, middle, and distal vagina were found in women with SUI. Nearly all of the domains of FSFI improved significantly after the vaginal laser treatment, except sexual desire. In conclusion, 3-D transperineal ultrasound can be used to conduct vaginal topography. After Er:YAG vaginal laser treatment, the anatomical changes of vaginal shrinkage and the improvement of female sexual function were both noted. The favorable outcome of sexual function partly related to the tightening of vagina, as evidenced by the measurements of the 3-D transperineal ultrasound.

Increasing CD44+/CD24(-) tumor stem cells, and upregulation of COX-2 and HDAC6, as major functions of HER2 in breast tumorigenesis.

BACKGROUND: Cancer cells are believed to arise primarily from stem cells. CD44+/CD24(-) have been identified as markers for human breast cancer stem cells. Although, HER2 is a well known breast cancer oncogene, the mechanisms of action of this gene are not completely understood. Previously, we have derived immortal (M13SV1), weakly tumorigenic (M13SV1R2) and highly tumorigenic (M13SV1R2N1) cell lines from a breast epithelial cell type with stem cell phenotypes after successive SV40 large T-antigen transfection, X-ray irradiation and ectopic expression of HER2/C-erbB2/neu. Recently, we found that M13SV1R2 cells became non-tumorigenic after growing in a growth factor/hormone-deprived medium (R2d cells). RESULTS: In this study, we developed M13SV1R2N1 under the same growth factor/hormone-deprived condition (R2N1d cells). This provides an opportunity to analyze HER2 effect on gene expression associated with tumorigenesis by comparative study of R2d and R2N1d cells with homogeneous genetic background except HER2 expression. The results reveal distinct characters of R2N1d cells that can be ascribed to HER2: 1) development of fast-growing tumors; 2) high frequency of CD44+/CD24(-) cells (~50% for R2N1d vs. ~10% for R2d); 3) enhanced expression of COX-2, HDAC6 mediated, respectively, by MAPK and PI3K/Akt pathways, and many genes associated with inflammation, metastasis, and angiogenesis. Furthermore, HER2 expression can be down regulated in non-adhering R2N1d cells. These cells showed longer latent period and lower rate of tumor development compared with adhering cells. CONCLUSIONS: HER2 may induce breast cancer by increasing the frequency of tumor stem cells and upregulating the expression of COX-2 and HDAC6 that play pivotal roles in tumor progression.

Predictors of voiding dysfunction following Uphold™ mesh repair for the treatment of pelvic organ prolapse.

OBJECTIVE: To identify factors associated with voiding dysfunction after Uphold™ transvaginal mesh (TVM) repair in women with pelvic organ prolapse (POP). STUDY DESIGN: We performed a retrospective analysis of 110 women with symptomatic pelvic organ prolapse (POP), anterior vaginal wall prolapse and/or apical prolapse (stage II to IV) who were scheduled for Uphold™ mesh surgery from September 2015 through December 2016. All subjects underwent urinalyses, UDI-6, IIQ-7, ICI-Q, POPDI-6, and pelvic examinations using the POP quantification (POP-Q) staging system before and after surgeries, with follow-up durations ranging from 24-36 months. RESULTS: A total of 12 (10.9 %) of 110 women reported voiding dysfunction after Uphold™ mesh surgery. Using univariate analysis, there were no differences in body mass index and urodynamic parameters between normal voiding group and dysfunctional voiding group (P > 0.05). However, in patients aged above 71, POPDI-6 score≧13, preoperative concomitant urinary hesitancy, and incomplete emptying were found to be significant predictors of voiding dysfunction following Uphold™ mesh surgeries (P < 0.05). CONCLUSION: In patients aged above 71, POPDI-6 score≧13, preoperative concomitant urinary hesitancy, and incomplete emptying were significant predictors of voiding dysfunction after Uphold™.

MiR­381 regulates cell motility, growth and colony formation through PIK3CA in endometriosis­associated clear cell and endometrioid ovarian cancer.

Ovarian cancer is the one of the most lethal gynecological cancer types. MicroRNAs (miRs) are noncoding RNAs that modulate the translation of their target mRNAs via binding to a complementary sequence in the target 3' untranslated region, and the dysregulation of certain miRs has been demonstrated to contribute to cancer progression. In this regard, the current study extended our previous work and used next­generation sequencing data to search for upstream regulators of genetic alterations that are common in ovarian cancer, as well as the miRs that are involved in controlling the expression of these regulators. An miR prediction program was used to identify miR­381 as an upstream regulator of phosphatidylinositol 3­kinase catalytic subunit α (PIK3CA) in the context of ovarian cancer. Levels of miR­381 were decreased in clear cell and endometrioid carcinoma ovarian cancer. Experimentally induced upregulation of miR­381 led to a decrease in the level of PIK3CA in ovarian cancer cells. Furthermore, experimentally induced upregulation of miR­381 inhibited the proliferation of ovarian cancer cells in vitro and their ability to form colonies and migrate. The observed decrease in miR­381 in ovarian cancer could be reversed upon overexpression of the gene encoding the tumor suppressor homeobox D10. The current results highlight the role of miR­381­mediated regulation of PIK3CA in the development and progression of ovarian cancer and suggest that restoration of miR­381 to normal levels in ovarian cancer cells may constitute a therapeutic strategy for patients.

Risk factors and survival of early bleeding after esophageal variceal ligation.

BACKGROUND/AIMS: In cirrhotic patients, esophageal variceal bleeding (EVB) is still unpredictable and continues despite initial adequate treatment that is associated with great mortality. Bacterial infections are frequently diagnosed in cirrhotic patients with gastrointestinal bleeding (GIB). The aims of this study were to analyze the clinical risk factors and survival of early bleeding after endoscopic variceal ligation (EVL). METHODOLOGY: A total of 96 cirrhotic patients with esophageal varices who received elective or emergent EVL procedure were analyzed. The variables for risk factors analysis included bacterial infection, hepatocellular carcinoma (HCC) with or without portal vein thrombosis, etiology of cirrhosis, Child-Pugh status, and basic laboratory data. There were 19 patients with bleeding episode or rebleeding within 14 days after EVL. The remaining 77 patients were without bleeding event after EVL. RESULTS: Patients with Child C cirrhosis (odds ratio, 7.27; 95% CI, 2.20-24.07, P = 0.001) and bacterial infection (odds ratio, 130.29; 95% CI, 14.70-1154, P < 0.001) were independently associated with the early bleeding after EVL. However, there was no significant difference in long-term survival between patients with and without early bleeding after EVL. CONCLUSIONS: Bacterial infection and end-stage liver cirrhosis (Child C) are the independent risk factors for early bleeding after EVL. We should closely monitor the symptoms/signs of infection and empirical antibiotics should be administered once infection is suspected or documented, especially in cirrhotic patients with poor liver reserve.

Benzyl butyl phthalate decreases myogenic differentiation of endometrial mesenchymal stem/stromal cells through miR-137-mediated regulation of PITX2.

Phthalate, an environmental toxin, has been considered as an endocrine-disrupting chemical. Growing evidence has demonstrated links between endocrine-disrupting chemicals, tissue development, and reproductive physiology, but the mechanisms of gene expression regulation by environmental factors that affect cell differentiation are unclear. Herein, we investigated the effects of butyl benzyl phthalate (BBP) on human endometrial mesenchymal stem/stromal cell (EN-MSC) differentiation and identified a novel signaling pathway. Differentiation of endometrial mesenchymal stem/stromal cells decreased after administration of BBP. We analyzed BBP regulation of gene expression in EN-MSC using cDNA microarrays and Ingenuity Pathway Analysis software to identify affected target genes and their biological functions. PITX2 emerged as a common gene hit from separate screens targeting skeletal and muscular disorders, cell morphology, and tissue development. BBP decreased transcription of PITX2 and elevated expression of the microRNA miR-137, the predicted upstream negative regulator of PITX2. These data indicated that BBP affects PITX2 expression through miR-137 targeting of the 3' untranslated region of PITX2 mRNA. PITX2 down-regulation also decreased MyoD transcript levels in EN-MSC. Our results demonstrate that BBP decreases EN-MSC myogenic differentiation through up-regulation of miR-137, contribute to our understanding of EN-MSC differentiation, and underline the hazardous potential of environmental hormones.

Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling.

Understanding the regulatory mechanisms unique to breast cancer stem cells (BCSCs) is required to control breast cancer metastasis. We found that phthalates promote BCSCs in human breast cancer cell cultures and xenograft tumors. A toxic phthalate, benzyl butyl phthalate (BBP), activated aryl hydrocarbon receptor in breast cancer cells to stimulate sphingosine kinase 1 (SPHK1)/sphingosine 1-phosphate (S1P)/sphingosine-1-phosphate receptor 3 (S1PR3) signaling and enhance formation of metastasis-initiating BCSCs. BBP induced histone modifications in S1PR3 in side population (SP) cells, but not in non-SP cells. SPHK1 or S1PR3 knockdown in breast cancer cells effectively reduced tumor growth and lung metastasis in vivo. Our findings suggest S1PR3 is a determinant of phthalate-driven breast cancer metastasis and a possible therapeutic target for regulating BCSC populations. Furthermore, the association between breast carcinogenesis and environmental pollutants has important implications for public health.

Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer.

UNLABELLED: Recent molecular and pathological studies suggest that endometriosis may serve as a precursor of ovarian cancer (endometriosis-associated ovarian cancer, EAOC), especially of the endometrioid and clear cell subtypes. Accordingly, this study had two cardinal aims: first, to obtain mutation profiles of EAOC from Taiwanese patients; and second, to determine whether somatic mutations present in EAOC can be detected in preneoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from ten endometriosis patients with malignant transformation. Macrodissection was performed to separate four different types of cells from FFPE sections in six patients. The four types of samples included normal endometrium, ectopic endometriotic lesion, atypical endometriosis, and carcinoma. Ultra-deep (>1000×) targeted sequencing was performed on 409 cancer-related genes to identify pathogenic mutations associated with EAOC. The most frequently mutated genes were PIK3CA (6/10) and ARID1A (5/10). Other recurrently mutated genes included ETS1, MLH1, PRKDC (3/10 each), and AMER1, ARID2, BCL11A, CREBBP, ERBB2, EXT1, FANCD2, MSH6, NF1, NOTCH1, NUMA1, PDE4DIP, PPP2R1A, RNF213, and SYNE1 (2/10 each). Importantly, in five of the six patients, identical somatic mutations were detected in atypical endometriosis and tumor lesions. In two patients, genetic alterations were also detected in ectopic endometriotic lesions, indicating the presence of genetic alterations in preneoplastic lesion. Genetic analysis in preneoplastic lesions may help to identify high-risk patients at early stage of malignant transformation and also shed new light on fundamental aspects of the molecular pathogenesis of EAOC. KEY MESSAGES: Molecular characterization of endometriosis-associated ovarian cancer genes by targeted NGS. Candidate genes predictive of malignant transformation were identified. Chromatin remodeling, PI3K-AKT-mTOR, Notch signaling, and Wnt/ß-catenin pathway may promote cell malignant transformation.

Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) has been reported to be more sensitive and specific in diagnosing hepatocellular carcinoma (HCC) when compared with alpha-fetoprotein (AFP). However, its ability to identify small HCC still remains unclear. Thus, we conducted a cross-sectional case control study to evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77% and 86.4% vs 68.5%, 59% and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.

Delayed postpartum hemorrhage--a rare clinical presentation of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: a case report.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are rare and closely related disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Many risk factors have been reported including infection, cancer, pregnancy, a variety of drugs (e.g. anticancer drugs), and autoimmune diseases. The incidence of TTP-HUS is higher in females than in males, especially during pregnancy and the immediate postpartum period. Review of the literature reveals that delayed postpartum hemorrhage is a rare clinical presentation of TTP-HUS. We report a case of TTP-HUS with recurrent delayed postpartum hemorrhage and dismal outcome.

Urothelial carcinoma arising from an ovarian mature cystic teratoma.

OBJECTIVE: Ovarian mature cystic teratomas with malignant transformation are rare, and squamous cell carcinoma is the most common pathological entity. Among these malignant transformations, urothelial cell carcinoma is rare. CASE REPORT: We report a woman presenting with a huge pelvic cystic mass, favoring a right ovarian mature cystic teratoma with malignant transformation, based on magnetic resonance imaging, who was successfully treated with surgery. CONCLUSION: The final pathology confirmed concomitant malignant transformation of urothelial carcinoma.

Dynamic Trk and G Protein Signalings Regulate Dopaminergic Neurodifferentiation in Human Trophoblast Stem Cells.

Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells. Intracranial implantation of such neural progenitor cells into the 6-OHDA-lesioned substantia nigra pars compacta successfully regenerates dopaminergic neurons and integrity of the nigrostriatal pathway, ameliorating the behavioral deficits in the Parkinson's disease rat model. Here, we demonstrated a dynamic molecular network in systematic analysis by addressing spatiotemporal molecular expression, intracellular protein-protein interaction and inhibition, imaging study, and genetic expression to explore the regulatory mechanisms of RA induction in the differentiation of human trophoblast stem cells to DA committed progenitor cells. We focused on the tyrosine receptor kinase (Trk), G proteins, canonical Wnt2B/ß-catenin, genomic and non-genomic RA signaling transductions with Tyrosine hydroxylase (TH) gene expression as the differentiation endpoint. We found that at the early stage, integration of TrkA and G protein signalings aims for axonogenesis and morphogenesis, involving the novel RXRα/Gαq/11 and RARß/Gß signaling pathways. While at the later stage, five distinct signaling pathways together with epigenetic histone modifications emerged to regulate expression of TH, a precursor of dopamine. RA induction generated DA committed progenitor cells in one day. Our results provided substantial mechanistic evidence that human trophoblast stem cell-derived neural stem cells can potentially be used for neurobiological study, drug discovery, and as an alternative source of cell-based therapy in neurodegenerative diseases like Parkinson's disease.

Disability in patients with chronic neck pain: heart rate variability analysis and cluster analysis.

OBJECTIVES: Adequately addressing the scope of disability in patients with chronic neck pain is crucial in a clinical setting. The aim of this study was to determine the disease profile of patients with chronic neck pain and to analyze the factors related to the level of disability. METHODS: We studied 121 patients with chronic neck pain. The following data were obtained from the participants: Chinese Health Questionnaire-12, the Pittsburgh Sleep Quality Index, the visual analog scale to pain, pressure pain threshold, the Neck Disability Index, and heart rate variability analysis. Cluster analysis was performed to divide patients into separate groups according to their presentations. A Pearson correlation was computed to analyze factors correlated with disability (Neck Disability Index). The significance level was set at P<0.05. RESULTS: Cluster analysis yielded 3 groups of patients with distinct features. Group I had a sex composition similar to the original population, was younger, and displayed the lowest overall deficits. Group II included middle-to-older-aged women, and presented with a higher level of pain, psychological distress, sleep disorder, and disability. Group III, comprising middle-to-older-aged men, showed moderate symptom severity. Correlation revealed that the factors significantly associated with a high degree of disability were low heart rate variability, high pain intensity, older age, poor sleep quality, and high psychological distress. DISCUSSION: We suggest that 3 distinct subgroups of patients with chronic neck pain exhibit particular features. Furthermore, reduced heart rate variability was associated with subjective disability in these patients. Further study is advised to establish the pathologic mechanism and clinical applications of our findings.

Possible mechanism of phthalates-induced tumorigenesis.

Phthalates--substances used in the manufacture of plastics--are considered as possible human carcinogens and tumor-promoting agents. The worldwide annual production of plastics surpassed 300 million tons in 2010. Plastics are an indispensable material in modern society, and many products manufactured from plastics are a boon to public health; however, plastics also pose health risks. Animal studies have indicated that phthalates are carcinogenic, but human epidemiological data confirming this carcinogenicity in humans are limited. The activation of peroxisome proliferator-activated receptor α (PPARα), which has been observed in rodent carcinogenesis, has not been observed in humans. Here, we review the hypothesis that the aryl hydrocarbon receptor (AhR) and its downstream signaling cascade promote phthalate-induced tumorigenesis.

Benzyl butyl phthalate induces necrosis by AhR mediation of CYP1B1 expression in human granulosa cells.

We investigated the signaling pathway of the arylhydrocarbon receptor (AhR) on HO23 cells (immortalized human granulosa cells (hGC)) mediated by benzyl butyl-phthalate (BBP). BBP (1 µM) significantly increased the mRNA and protein levels of AhR, aryl hydrocarbon receptor nuclear translocator (ARNT) and cytochrome-P450 (CYP)1B1 in HO23 cells. Treatment with 3',4'-dimethoxyflavone (3',4'-DMF) or AhR siRNA significantly reduced AhR and CYP1B1, but CYP1A1 was not affected by 3',4'-DMF or AhR siRNA, suggesting that increases in CYP1A1 may not regulated by AhR. BBP induced the AhR fusion protein to localize and accumulate around the nucleus, and AhR heterodimerization with ARNT was observed in the nucleus by immunoprecipitation. Chromatin immunoprecipitation and reporter assays revealed the effect of BBP on CYP1B1, but not CYP1A1. Necrosis was significantly increased in HO23 cells after BBP treatment, and 3',4'-DMF, AhR siRNA or CYP1B1 siRNA knockdown blocked this phenomenon. These data suggest that BBP-induced HO23 cell necrosis is AhR and CYP1B1 dependent.

Resectoscopic treatment of ectopic pregnancy in previous cesarean delivery scar defect with vasopressin injection.

OBJECTIVE: To describe resectoscopic treatment with vasopressin injection as an effective surgical intervention for ectopic pregnancy in previous cesarean delivery scar (PCDS) defect. DESIGN: Case report. SETTING: University hospital. PATIENT(S): Two women with ectopic pregnancy in PCDS defect. INTERVENTION(S): The patients underwent transvaginal ultrasound examination, followed by operative hysteroscopy with vasopressin injection for evacuating the ectopic pregnancy in PCDS defect. MAIN OUTCOME MEASURE(S): Conservation of the uterus. RESULT(S): Successful resectoscopic treatment of ectopic pregnancy in PCDS defect. CONCLUSION(S): Resectoscopic treatment of ectopic pregnancy in PCDS defect is a safe and efficient technique that has the advantage of a rapid return to normal levels of ß-hCG. Intracervical vasopressin administration could decrease intraoperative bleeding and provide a clear view during the operation.