APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer.

BACKGROUND: Recent studies have demonstrated that APOC1 is associated with cancer progression, exerting cancer-promoting and immune infiltration-promoting effects. Nevertheless, there is currently no report on the presence of APOC1 in ovarian cancer (OV). METHOD: In this study, we conducted data analysis using the GEO and TCGA databases. We conducted a thorough bioinformatics analysis to investigate the function of APOC1 in OV, utilizing various platforms including cBioPortal, STRING, GeneMANIA, LinkedOmics, GSCALite, TIMER, and CellMarker. Additionally, we performed immunohistochemical staining on tissue microarrays and conducted in vitro cellular assays to validate our findings. RESULT: Our findings reveal that APOC1 expression is significantly upregulated in OV compared to normal tissues. Importantly, patients with high APOC1 levels show a significantly poorer prognosis. Furthermore, our study demonstrated that APOC1 exerted a crucial function in promoting the capacity of ovarian cancer cells to proliferate, migrate, and invade. Additionally, we have identified that genes co-expressed with APOC1 are primarily associated with adaptive immune responses. Notably, the levels of APOC1 in OV exhibit a correlation with the presence of M2 Tumor-associated Macrophages (TAMs). CONCLUSION: APOC1 emerges as a promising prognostic biomarker for OV and exhibits a significant association with M2 TAMs in OV.

Preparation and Characterization of a Photo-Crosslinked Methacryloyl-Collagen Composite Film to Promote Corneal Nerve Regeneration via Surface Grafting of Taurine Molecules.

Blindness is frequently caused by corneal abnormalities, and corneal transplantation is the most effective treatment method. It is extremely important to develop high-quality artificial corneas because there are not enough donor corneas accessible for cornea transplantation. One of the most-often utilized materials is collagen, which is the primary component of natural cornea. Collagen-based corneal repair materials have good physicochemical properties and excellent biocompatibility, but how to promote the regeneration of the corneal nerve after keratoplasty is still a big challenge. In this research, in order to promote the growth of nerve cells on a collagen (Col) substrate, a novel collagen-based material was synthesized starting from the functionalization of collagen with unsaturated methacryloyl groups that three-dimensionally photopolymerize to a 3D network of chemically crosslinked collagen (ColMA), onto which taurine molecules were eventually grafted (ColMA-Tr). The physicochemical properties and biocompatibility of the Col, ColMA and ColMA-Tr films were evaluated. By analyzing the results, we found that all the three samples had good moisture retention and aq high covalent attachment of methacryloyl groups followed by their photopolymerization improved the mechanical properties of the ColMA and ColMA-Tr. Most importantly, compared with ColMA, the taurine-modified collagen-MA film significantly promoted the growth of nerve cells and corneal epithelial cells on its surface. Our preliminary results suggest that this novel ColMA-Tr film may have potential use in cornea tissue engineering in the future.

BMDCs induce the generation of the CD103+CD8+ tissue-resident memory T cell subtype, which amplifies local tumor control in the genital tract.

Tissue-resident memory T (Trm) cells can trigger a secondary immune response when they encounter the same antigen, playing an important role in antitumor immunity. However, whether Trm cells are protective against female genital tract tumors remainunknown. Here, we show that cervicovaginal vaccination with HPV16 E7aa43-62peptide/CPG-1826 can generate CD103+CD8+Trm cells in the genital tract. These Trm cells can result in subsequent CD8+ T cell expansion and cytokine production when they encounter the same antigen. Importantly, this secondary response can control rechallenge with tumor cells. In vitro,BMDCs can promote the production of TGF-ß, which induces CD103 expression in CD8+ T cells. In human cervical cancer samples, DCs were correlated with the Trm gene signature, which was positively associated with overall survival. Our results indicate that cervicovaginal Trm cells have the capacity tocontrol tumor growth and that BMDCs may induce Trm cell generation via the TGF-ß signaling pathway.

Clinical characteristic and prognostic factors in high-grade endometrial neuroendocrine carcinoma.

AIM: The aim of the present study was to summarize the clinical characteristics and analyze the independent prognostic factors in patients with high-grade endometrial neuroendocrine carcinoma (ENC). METHODS: Patients diagnosed with ENC, endometrioid adenocarcinoma (EAC), endometrial clear-cell carcinoma (ECC), endometrial serous carcinoma (ESC), endometrioid carcinoma with mucinous features (EMC) from 1987 to 2016 were screened from the National Cancer Institute database (surveillance, epidemiology, and end results [SEER]). Kaplan-Meier were used to assess survival. Univariate and multivariate Cox proportional hazards analysis were done to examine factors affecting survival. RESULTS: The median survival times of ENC were 11 months, shorter than that of EAC, ECC, ESC, and EMC (p < 0.01). There was no significant difference in ages, survival rate, and median survival time between large-cell ENC (LCENC) and small-cell ENC (SCENC), which were all belong to ENC. In a multivariable model, the hazard ratio (HR) of death for women with Federation International of Gynecology and Obstetrics (FIGO) stage I-II of ENC was 0.37 compared to FIGO stage III-IV (p < 0.01). The HR of patients who under the surgery was 0.39 compared to the patients who without surgery (p < 0.01), and the HR of patients who received chemotherapy was 0.51 compared to the patients who did not received chemotherapy (p < 0.01). Radiotherapy did not significantly reduce the mortality risk of patients. CONCLUSION: ENC was a kind of devastating endometrial cancers with the poorest prognosis. Surgical treatment and chemotherapy were necessary for improving prognosis of ENC. Early diagnosis favored better prognosis. There was no prognostic difference between with and without radiotherapy.

LINC01133 contribute to epithelial ovarian cancer metastasis by regulating miR-495-3p/TPD52 axis.

Currently, there is increasing evidence that long noncoding RNAs (lncRNAs) initiate and promote the progression of epithelial ovarian cancer (EOC). In this study, we revealed the roles and the potential mechanisms of long intergenic non-protein coding RNA 1133 (LINC01133) in EOC, which remains not well understood. We found that LINC01133 was upregulated in EOC tissues and cell lines. Besides, it was associated with the clinicopathological feature of metastasis. Functional experiments demonstrated that LINC01133 could facilitate cancer cell migration and invasion in vitro and tumor metastasis in vivo. Further molecular mechanisms studies indicated that LINC01133 and miR-495-3p reciprocally repressed expression of each other. We also realized that LINC01133 shared the same binding sites for miR-495-3p with tumor protein D52 (TPD52). We confirmed that TPD52 functioned as a direct target of miR-495-3p and mediated the enhancing effect of LINC01133 on cancer metastasis. Generally, our study showed that LINC01133 interacted with miR-495-3p to promote metastasis in EOC by regulating TPD52. LINC01133 also provided a potential therapeutic perspective for future clinical treatment.

α-NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase-4 pathway.

Chemotherapy resistance is one of the most common causes of death among patients with ovarian cancer, and identifying novel antitumor agents is a priority. Here, we report that the novel molecule 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA) induces epithelial ovarian cancer (EOC) cell pyroptosis through the gesdermin-d (GSDMD)/caspase-4 pathway. Furthermore, Cell Counting Kit-8 fluorescence-activated cell sorting analysis showed that α-NETA treatment led to cell death in different ovarian cancer cell lines, including Ho8910, Ho8910PM, and A2780. Morphologic examination by electron microscopy indicated that cells treated with α-NETA produced multiple microbubbles, typical of cells undergoing pyroptosis. α-NETA also significantly increased expression of pyroptosis-associated molecules including caspase-4 and GSDMD in EOC cells. Knockdown of either caspase-4 or GSDMD in ovarian cancer cells strongly interfered with α-NETA cell-killing activity, indicating that α-NETA acts through the pyroptosis pathway. In vivo, α-NETA treatment dramatically decreased the size of EOC tumors in mice. Our findings suggest that α-NETA represents a potential new antitumor molecule or lead compound for EOC chemotherapy.-Qiao, L., Wu, X., Zhang, J., Liu, L., Sui, X., Zhang, R., Liu, W., Shen, F., Sun, Y., Xi, X. α-NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase-4 pathway.

Expression of immune cell markers and tumor markers in patients with cervical cancer.

OBJECTIVE: Cervical cancer is one of the most common cancers worldwide, and immune function may impact disease progression. Serum markers may also be associated with diagnosis and progression. The aim of this study was to explore the clinical usefulness of determining the levels of peripheral blood immune cells and serum tumor markers in predicting diagnosis and prognosis of patients with cervical cancer. METHODS: 82 patients with cervical cancer (early stage group: IA-IB1 and IIA1; locally advanced group: IB2 and IIA2), 54 patients with cervical intra-epithelial neoplasia (CIN), and 54 healthy women (control group) were recruited. Inclusion criteria were: (1) patients whose cervical lesions were determined based on biopsy; and (2) patients who had not undergone immunotherapy, chemotherapy, or radiotherapy. The exclusion criteria were as follows: (1) patients with a history of other malignant tumors; (2) patients with heart, kidney, and other organ failure; (3) patients with immune diseases; and (4) pregnant or lactating women. The levels of immunocytes and tumor markers were assayed. The relationships among histopathologic factors were analyzed. The correlation between the levels of immunocytes and tumor markers in patients with different degrees of cervical lesions (pre-invasive or cancer) and healthy women was evaluated. RESULTS: The squamous cell carcinoma antigen and carcinoembryonic antigen levels in the control group and the CIN group were significantly lower than those in the cervical cancer groups (p<0.01). The incidence of lymph node metastasis in the early stage and locally advanced groups were 22.9% (11/48) and 46.2% (12/26), respectively, and 58.8% (20/34) and 7.5% (3/37) in the positive and negative lymphovascular invasion groups, respectively (p<0.05). The levels of CD8+ and CD8+ CD28+ T cells in the early stage group were markedly lower than those in the CIN group and the control group (p=0.014, p=0.008, respectively). The ratio of CD4+CD25+/CD4+ in the cervical cancer groups was significantly higher than in the control group (p<0.01). The increased serum squamous cell carcinoma and carcinoembryonic antigen levels and CD4+CD25+/CD4+ ratio were risk factors for cervical cancer by logistic regression analysis (p<0.05). CONCLUSIONS: In patients with cervical cancer, immune function was impaired compared with that in healthy women and patients with CIN, while squamous cell carcinoma and carcinoembryonic antigen levels were increased. Combined detection of the levels of peripheral blood immune cells and serum tumor markers may be helpful for early detection, diagnosis, and prognosis evaluation of patients with cervical cancer.

MiR-369-3p participates in endometrioid adenocarcinoma via the regulation of autophagy.

BACKGROUND: The aim of this study is to examine miRNA profiling and miR-369-3p participates in endometrioid adenocarcinoma (EEC) via the regulation of autophagy. METHODS: EEC and its adjacent normal tissues were obtained from 20 clinical patients after surgery. MiRNA profiling was performed using next generation sequencing (NGS) and was validated with quantitative real time PCR (qRT-PCR). qRT-PCR was also employed to measure miR-369-3p and autophagy-related protein 10 (ATG10) expression levels. Western blotting assay was performed to measure the expressions of ATG10 and LC3B. Luciferase reporter assay was conducted to confirm the direct targeting of ATG10 by miR-369-3p. Cell proliferation and migration assays were utilized to analyze the role of miR-369-3p in HEC-1-A cells. RESULTS: We found that miR-369-3p expression levels were down-regulated in EEC compared to the control tissues. The overexpression of miR-369-3p inhibited cell proliferation and migration in EEC; furthermore, ATG10 expression increased in EEC tissues. ATG10 was found to be a potential target of miR-369-3p via a dual-luciferase reporter assay, and ATG10 was shown to be down-regulated by miR-369-3p in protein levels. CONCLUSIONS: This study revealed that miR-369-3p inhibited cell proliferation and migration by targeting ATG10 via autophagy in EEC.

Downregulation of Mad2 and BubR1 increase the malignant potential and nocodazole resistance by compromising spindle assembly checkpoint signaling pathway in cervical carcinogenesis.

AIM: To explore the involvement of Mad2 and BubR1 in cervical carcinogenesis. METHODS: The expressions of Mad2 and BubR1 in tissues of high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and chronic cervicitis were analyzed immunohistochemistrily and compared with those of p16INK4A . PEGFP-Mad2 and pEGFP-BubR1 were transfected into SiHa cells to overexpress Mad2 and BubR1 and Si-RNAs to knockdown. Cell viability was measured by cell counting kit-8 (CCK-8) assay. Migration and invasion capabilities were detected by Transwell. Propidium iodide staining with flow cytometry was used for cell cycle analysis and apoptosis was detected using Annexin V/7-AAD staining after nocodazole treatment. RESULTS: The expression of Mad2 was significantly lower in HSIL than those in chronic cervicitis and LSIL, however, the expression of BubR1 showed no significant differences. To detect HSIL in cervical lesions, Mad2 had a sensitivity of 88.44% and a specificity of 87.23%, Mad2 was less sensitive and more specific than p16INK4a . In SiHa cells, knockdown of Mad2 and BubR1 increased cell growth, reinforced invasion capacity and migration potency, inhibited apoptosis and decreased G2-phase distribution after nocodazole treatment. Oppositely, the overexpression strategies made cells show decreased malignant behaviors, raised apoptosis and increased G2-phase distribution. CONCLUSION: Mad2 negativity was specific to identify HSIL immunohistochemistrily. Downregulation of Mad2 and BubR1 increase the malignant behavior and nocodazole resistance of SiHa cells via causing spindle assembly checkpoint defect. This mechanism may contribute to cervical carcinogenesis and resistance to microtubule-targeting drugs.

[Effect of umbilical cord mesenchymal stem cells on proliferation and apoptosis of ovarian cancer cells].

OBJECTIVE: To observe the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on the proliferation and apoptosis of human ovarian cancer cell SKOV3.
 Methods: Transwell co-culture was used to observe the targeted homing effect of UC-MSCs on ovarian cancer cells. MTT assay was used to detect the inhibitory effect of UC-MSCs conditioned medium on SKOV3 proliferation, and Annexin V-FITC/PI double staining was used to detect the apoptotic rate. Real-time PCR was used to detect the expression levels of Ki-67, Bcl-2 and Bax genes-relevant to proliferation and apoptosis of SKOV3 cells.
 Results: UC-MSCs targeted SKOV3 cells in vitro. MTT assay showed that UC-MSCs conditioned medium significantly inhibited the proliferation of SKOV3 cells (P<0.01). Annexin V-FITC/PI double staining showed that the apoptotic rate in the 75% conditioned medium group was significantly higher than that in the control group (P<0.05). Real-time PCR showed that the expression of proliferation-related gene Ki-67 decreased significantly (P<0.01). The apoptosis-related gene Bcl-2 expression was decreased dramatically (P<0.01), and Bax expression was increased significantly (P<0.01).
 Conclusion: UC-MSCs can target ovarian cancer cells in vitro, inhibit the proliferation of SKOV3 cells by regulating the expression of Ki-67, and promote the apoptosis of SKOV3 cells by regulating the expression of Bcl-2 and Bax.

Capn4 Enhances Osteopontin Expression through Activation of the Wnt/ß-Catenin Pathway to Promote Epithelial Ovarian Carcinoma Metastasis.

BACKGROUND AND AIM: Increasing evidence shows that the calpain regulatory subunit Capn4 can modulate the proliferation and metastasis of cancer cells, and plays an important role in the development of malignant tumors. However, there is no information on the clinical significance of Capn4 in epithelial ovarian carcinoma (EOC) or the molecular mechanisms by which Capn4 promotes the growth and metastasis of EOC. Therefore, the aim of this study was to clarify the role of Capn4 in EOC. METHODS: We evaluated Capn4 and osteopontin (OPN) expression in EOC cell lines and tissues from patients with ovarian cancer by western blotting and immunohistochemical analysis. We then created cell lines with downregulated and upregulated Capn4 expression, using Capn4-targeting small interfering RNA and a pcDNA3.1-Capn4 overexpression vector, respectively, to investigate its function in EOC in vitro. In addition, we investigated the potential mechanism underlying the function of Capn4 by examining the effect of modifying Capn4 expression on Wnt/ß-catenin signaling pathway-related genes by western blotting. RESULTS: Capn4 was overexpressed in clinical EOC tissues compared with that in normal ovarian epithelial tissue, and was associated with poor clinical outcomes. Upon silencing or overexpressing Capn4 in EOC cells, we concluded that Capn4 promotes cell proliferation and migration in vitro. Furthermore, Capn4 promoted EOC metastasis by interacting with the Wnt/ß-catenin signaling pathway to upregulate OPN expression. CONCLUSION: Our study indicates that Capn4 plays a critical role in the progression and metastasis of EOC, and could be a potential therapeutic target for EOC management.

Over-expression of CHAF1A in Epithelial Ovarian Cancer can promote cell proliferation and inhibit cell apoptosis.

Chromatin Assembly Factor 1, subunit A (CHAF1A) can regulate cell proliferation, DNA repair and epigenetic changes in embryonic stem cells and it has been reported that over-expression of CHAF1A is associated with several human diseases including cancer. However, the expression and function of CHAF1A in Epithelial Ovarian Cancer (EOC) are rarely reported at present. In this study, we found that the positive staining of CHAF1A in EOC was higher than that in normal tissues and over-expression of CHAF1A was strongly associated with cancer stage and lymph node metastasis. Knockdown of CHAF1A by siRNA in EOC inhibited cell proliferation, reduced colony formation, caused G0/G1 phase arrest and promoted cell apoptosis. Taken together, the high expression of CHAF1A promotes cell proliferation and inhibits cell apoptosis and CHAF1A may be developed as a prognosis biomarker and potential therapeutic target of EOC.

TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation.

Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation.

The role of the SDF-1/ CXCR7 axis on the growth and invasion ability of endometrial cancer cells.

PURPOSE: Stroma-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) are involved in human endometrial carcinoma (EC) progression. CXCR7 is another important receptor of SDF-1 and has a higher affinity with SDF-1 compared with that of CXCR4. This paper aims to study the effects of the SDF-1/CXCR7 axis on the growth and invasion ability of EC cells. METHODS: CXCR7 expression was evaluated by quantitative RT-PCR, immunohistochemistry, immunocytochemistry and Western blotting in EC cell lines and 30 cases of primary EC tissue from patients. EC cell line proliferation and migration were assessed following knockdown of CXCR7 by MTT and transwell assays. RESULTS: The results showed that CXCR7 was highly expressed at both mRNA and protein levels in the EC cells and tissue. siCXCR7 effectively silenced CXCR7 in Ishikawa and AN3CA cells. Treatment with 17ß-oestradiol (17ß-E2) significantly increased the levels of CXCR7 and SDF-1 in Con, siCon and siCXCR7 treated Ishikawa. siCXCR7 persistently inhibited CXCR7 expression, even in cells treated with 17ß-E2. Moreover, in vitro functional analyses, silencing CXCR7 resulted in decreased proliferation in Ishikawa and AN3CA cells. Treatment with 17ß-E2 and SDF-1 significantly promoted the growth and migration in siCon treated Ishikawa and AN3CA. Interestingly, in response to 17ß-E2 and SDF-1 stimulation, siCXCR7 continuously inhibited the growth and invasion of Ishikawa and AN3CA cells. CONCLUSION: Our results indicate that SDF-1/CXCR7 plays a positive role in the proliferation and invasion of EC cells. CXCR7 inhibition treatment may provide a promising strategy for anti-tumour therapy for EC.

Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase.

Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.

NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer.

NANOG is a key transcription factor that is overexpressed and plays an important role in various cancers. Its overexpression is associated with highly tumorigenic, drug-resistant, and poor prognosis. However, the underlying mechanism of action of NANOG in ovarian cancer remains unclear. Epithelial-mesenchymal transition (EMT), which is a critical process in cancer invasion and metastasis, is also associated with drug resistance. We determined whether NANOG is associated with EMT and chemoresistance in epithelial ovarian cancer cells. NANOG expression was increased in epithelial ovarian cancer cells (HEY and SKOV3) compared with normal epithelial ovarian cells (Moody). Low expression of NANOG increased the expression of E-cadherin and decreased the expression of vimentin, ß-catenin, and Snail. Furthermore, the cell migration and invasion abilities were decreased. The multidrug resistance genes MDR-1 and GST-π were also downregulated when NANOG was lowly expressed. The cells that were transfected with the si-NANOG plasmid were more sensitive to cisplatin compared with the cells that were transfected with empty vector. The data demonstrated that Stat3 was correlated with NANOG-mediated EMT and drug resistance. The silencing of Stat3 expression abrogated NANOG-mediated EMT changes and increased the sensitivity of the cells to chemotherapy. These results suggest that NANOG mediates EMT and drug resistance through activation of the Stat3 pathway in epithelial ovarian cancer.

Management of Cesarean Scar Pregnancy Using Ultrasound-Guided Dilation and Curettage.

STUDY OBJECTIVE: To evaluate the potential risk factors associated with failed ultrasound-guided dilation and curettage (D&C) treatment of cesarean scar pregnancy (CSP). DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Fifty-one patients diagnosed with CSP and treated with ultrasound-guided D&C at Shanghai General Hospital of Shanghai Jiao Tong University. INTERVENTION: Lesion resection using ultrasound-guided D&C. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics, vaginal bleeding, abdominal pain, the size of the gestational sac, cardiac motion, blood flow around the gestational sac, cesarean scar thickness, and serum ß-human chorionic gonadotropin (ß-hCG) levels were compared between the successful operation group and the failed operation group. Cesarean scar thickness was the main risk factor that determined the success of ultrasound-guided D&C. The success rates were 50% and 97.67% for those with cesarean scars <3 mm thick and those with scars >3 mm thick, respectively (p = .001). The success rate was also associated with the abundance of blood flow surrounding the capsule and size of the gestational sac (p < .005). Surgical success was not affected by abnormal vaginal bleeding, abdominal pain, cardiac motion, or serum ß-hCG levels. CONCLUSION: Ultrasound-guided D&C is the first choice for treating CSP if the cesarean scar is >3 mm thick, blood flow is not abundant, and the maximum diameter of the gestational sac is <30 mm. A transabdominal procedure is preferred for patients with high-risk factors.

OCT4 mediates FSH-induced epithelial-mesenchymal transition and invasion through the ERK1/2 signaling pathway in epithelial ovarian cancer.

Our previous study showed that Octamer-binding transcription factor 4 (OCT4) expression was upregulated and significantly associated with histological grade through the analysis of OCT4 expression in 159 ovarian cancer tissue samples, and OCT4 mediated follicle-stimulating hormone (FSH)-induced anti-apoptosis in epithelial ovarian cancer. Nevertheless, whether OCT4 participates in FSH-induced invasion in ovarian cancer is still unknown. Therefore, the present study aimed to define whether FSH-induced ovarian cancer invasion is mediated by OCT4. In present study, we showed that FSH induced not only the epithelial-mesenchymal transition (EMT) and invasive phenotype but also the upregulation of OCT4 expression in a dose- and time-dependent manner in epithelial ovarian cancer cells. In addition, the expression of FSH receptor (FSHR) was upregulated by FSH induction, and knockdown of FSHR inhibited FSH-stimulated OCT4 expression. ERK1/2 signaling pathway participated in the enhanced expression of OCT4 and Snail induced by FSH. We further showed that the activated expression of Snail and N-cadherin, the suppressed expression of E-cadherin and the morphological change of the cells stimulated by FSH were blocked by OCT4-specific small interfering RNA. Moreover, our results showed that OCT4 mediated the increase in invasive capacity induced by FSH in ovarian cancer cells. Taken together, our work reveals that OCT4 is an essential mediator in FSH-induced EMT and invasion in epithelial ovarian cancer and may act as a potential therapeutic target.

Mouse Resistin (mRetn): cloning, expression and purification in Escherichia coli and the potential regulative effects on murine bone marrow hematopoiesis.

BACKGROUND: Resistin (Retn) is a cytokine which has a controversial physiological role regarding its involvement with obesity and type II diabetes mellitus. Recently, murine Retn was found to be a possibly potential regulator of hematopoiesis in mice shown in the screening results of a set of gene chips which mapped the expression level of murine genes during regeneration of impaired bone marrow (BM) by 5-fluorouracil. RESULTS: Recombinant mice Retn was expressed in Escherichia coli and purified using ion exchange chromatography. Totally 11.4 mg rmRetn was obtained from 500 ml culture with endotoxin level less than 1.0 EU/ug. The purity of recombinant murine Resistin reached to at least 97.6% via SDS-PAGE analysis and HPLC. The protein possessed chemotaxis effects in the mouse aortic endothelial cells in vitro in transwell analysis. In vitro, rmRetn could up regulate the CFU number of mice BM and after rmRetn was administered, the cell number of murine bone marrow was significantly increased in vivo after chemotherapy. Finally, rmRetn was found able to protect mice from the chemotoxicity of 5-fluorouracil. CONCLUSIONS: The discovery demonstrated a new function of murine Retn and suggested that it could potentially accelerate bone marrow regeneration post chemotherapy.

Risk factors for ectopic pregnancy: a multi-center case-control study.

BACKGROUND: Ectopic pregnancy (EP) is the leading cause of maternal death during the first trimester of pregnancy. A better understanding of EP risk can help prevent its occurrence. We carried out a multi-center, large-sample, case-control study to evaluate the risk factors for EP in Shanghai, China. METHODS: Women who were diagnosed with EP (n = 2411) and women with intrauterine pregnancies (n = 2416) were recruited from five hospitals in Shanghai, China. Information regarding the sociodemographic characteristics; reproductive, gynecological and surgical history; and previous and current use of contraceptives was collected from all participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted for potential confounding factors via multivariate logistic regression analysis. RESULTS: The study revealed that the risk of EP was associated with the traditional risk factors including previous EP (Adjusted odds ratio [AOR] = 2.72, 95% CI: 1.83-4.05), previous Chlamydia trachomatis infection (Adjusted OR = 3.18, 95% CI: 2.64, 3.84), previous infertility (AOR = 2.18, 95% CI: 1.66-2.88), previous adnexal surgery (AOR = 2.09, 95% CI: 1.49-2.93), previous appendectomy (AOR = 1.64, 95% CI: 1.13-2.37), and previous use of intrauterine devices (IUDs) (AOR = 1.72, 95% CI: 1.39-2.13). Additionally, EP risk was increased following the failure of most contraceptives used in the current cycle including IUDs (AOR = 16.43, 95% CI: 10.42-25.89), oral contraceptive pills (AOR = 3.02, 95% CI: 1.16-7.86), levonorgestrel emergency contraception (AOR = 4.75, 95% CI: 3.79-5.96), and female sterilization (AOR = 4 .73, 95% CI: 1.04-21.52). Stratified analysis showed that in vitro fertilization and embryo transfer (IVF-ET) was the main risk factor for EP in women with tubal infertility (AOR = 8.99, 95% CI: 1.98-40.84), although IVF-ET showed no association with EP in women with non-tubal infertility (AOR = 2.52, 95% CI: 0.14-44.67). CONCLUSION: In addition to the traditional risk factors, IVF-ET and current IUD use play dominant roles in the occurrence of EP. Attention should be given to women with tubal infertility who have undergone IVE-ET treatment.