Chemical composition of surgical smoke produced during the loop electrosurgical excision procedure when treating cervical intraepithelial neoplasia.

BACKGROUND: As LEEP (loop electrosurgical excision procedure) is being increasingly used for the diagnosis and treatment of uterine cervical intraepithelial neoplasia, surgical smoke during LEEP has become an inevitable health issue. Therefore, in this study, exposure to the chemical substances in surgical smoke produced during LEEP was assessed. METHODS: Smoke samples from patients with high-grade cervical intraepithelial neoplasia undergoing LEEP were collected by smoke-absorbing devices situated 1 m away from the operating table and near the nose of the operator during LEEP. Each plume sample was collected after 5 patients underwent LEEP, requiring 5 min for smoke collection for each patient. The chemicals of exposure to surgical smoke were assessed, and the hazard classes of these chemical components were evaluated by the International Agency for Research on Cancer. RESULTS: Qualitative analysis of the smoke produced during LEEP revealed a variety of potentially toxic chemicals under standard detection, such as benzene, toluene, xylene, ethylbenzene, styrene, butyl acetate, acrylonitrile, 1,2-dichloroethane, phenol, chlorine, cyanide, hydrogen cyanide and carbon monoxide. Additionally, the average concentration of carbon dioxide was 0.098 ± 0.015% during surgery and was higher than that before surgery (0.072 ± 0.007%, P < 0.001), and the concentration of formaldehyde was significantly higher during surgery (0.023 ± 0.009 mg/m3, P < 0.05) than before surgery (0.012 ± 0.001 mg/m3, P < 0.05). CONCLUSIONS: Most of the detected chemical concentrations in smoke generated during LEEP were below the exposure limits when local exhaust ventilation procedures were efficiently used. However, the concentrations of carbon dioxide and formaldehyde found in smoke were significantly higher after surgery. Wearing a high-filtration mask and using evacuation devices routinely and consistently when performing LEEP are recommended to protect perioperative personnel.

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction.

Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.

Prognostic values of transketolase family genes in ovarian cancer.

Transketolase genes are key rate-limiting enzymes in the non-oxidative part of the pentose phosphate pathway, which is an important metabolic pathway in ribose-5-phosphate production. Three human transketolase genes have been identified: Transketolase (TKT), transketolase-like gene 1 (TKTL1) and transketolase-like gene 2 (TKTL2). Transketolase genes serve crucial roles in the tumorigenesis, metastasis and outcome of multiple types of cancer. However, the expression levels and prognostic values of transketolase family genes in patients with ovarian cancer remain unclear. The purpose of the study was to analyze the expression level and prognostic significance of transketolase family genes in ovarian cancer. In the present study, the mRNA expression levels of three transketolase genes in ovarian cancer and normal ovarian tissue were compared by Oncomine. The prognostic values of these genes were systemically assessed using the Kaplan-Meier plotter database. In addition, the associations between the mRNA levels of these transketolase genes and the clinicopathological characteristics of patients with ovarian cancer, such as histological subtype, clinical stage, grade, tumor protein p53 (TP53) mutation status and chemotherapy history were studied. The prognostic roles of transketolase genes were also evaluated in a validation dataset. The results demonstrated that TKT and TKTL1 expression in ovarian cancer tissues was elevated compared with that in normal ovarian tissues. In addition, high mRNA expression of the three transketolase genes was identified to be associated with poorer progression-free survival (PFS) in patients with serous ovarian cancer, especially in patients at an advanced stage. TKTL2 was significantly associated with poor overall survival in all patients with ovarian cancer. Additionally, transketolase family genes served a role in predicting PFS in patients with ovarian cancer treated with platinum and/or taxol. High expression of the three transketolase genes was associated with unfavorable PFS in patients with TP53-mutated ovarian cancer, but not in patients with TP53 wild-type ovarian cancer. These results suggested that transketolase family genes may serve important roles in the prognosis of patients with ovarian cancer.

Mifepristone inhibits IGF-1 signaling pathway in the treatment of uterine leiomyomas.

PURPOSE: To investigate the role of IGF-1 signaling pathway in the treatment of uterine leiomyomas with mifepristone. PATIENTS AND METHODS: From October 2015 to December 2018, 50 patients with uterine leiomyoma were included in this study. Overexpression or siRNA of IGF-1 in primary human uterine leiomyoma cells were treated with or without mifepristone. MTT was used to evaluate cell viability in assays of cell proliferation and cytotoxicity. IGF-1 expression in the cells was measured with real-time RT-PCR and Western blotting and manipulated with lentivirus ectopic overexpression or siRNA silencing. RESULTS: Inhibition of cell viability by mifepristone was found dependent on drug concentration and treatment time. IGF-1 and phosphorylation-ERK1/2 expression were decreased, while phosphorylation-AKT expression was increased after mifepristone treatment. IGF-1 significantly promoted cell growth, while IGF-1 knockdown and mifepristone showed synergistic inhibition effects on cell growth. The overexpression of IGF-1 reversed the inhibition of cell growth and ERK1/2 phosphorylation but showed no effect on AKT phosphorylation. CONCLUSION: Our study for the first time demonstrated that IGF-1 signaling via ERK1/2 appears to be an important target of mifepristone in the treatment of uterine leiomyomas, which may provide a new approach to avoid leiomyoma re-growth after cessation of mifepristone.

Human papillomavirus DNA in surgical smoke during cervical loop electrosurgical excision procedures and its impact on the surgeon.

Objective: The purpose of this study was to explore whether human papillomavirus (HPV) DNA is present in surgical smoke generated by loop electrosurgical excision procedures (LEEPs). Furthermore, we investigated the impact of this HPV DNA on surgeons. Methods: A total of 134 outpatients with persistent HPV infections treated with LEEP for cervical intraepithelial neoplasia between 2015 and 2016, along with the corresponding LEEP operators, were included. The flow fluorescence in situ hybridization technique was used to detect HPV DNA in exfoliated cervical cells from the patients, in surgical smoke and in nasal epithelial cells from the surgeons before and after LEEP. Results: The positive rates of HPV DNA in the three types of samples mentioned above were 94.8%, 29.9% and 1.5%, respectively. The distribution of HPV subtypes in surgical smoke was identical to that in the cervical specimens. The positive rate of HPV DNA in surgical smoke was significantly increased for greater distances of the suction device from the surgical site. The nasal epithelial cells of two surgeons were positive for HPV DNA, and the genotypes were consistent with those in the corresponding surgical smoke. After a 3-6-month follow-up, the nasal swabs from these two doctors tested negative for HPV DNA. Conclusions: This study demonstrated the presence of HPV DNA in surgical smoke produced by LEEP and the risk of airborne transmission of HPV DNA during the operation. Fortunately, the HPV DNA in the nasopharynx of the operators was not persistent.

Differential effects of GLI2 and GLI3 in regulating cervical cancer malignancy in vitro and in vivo.

Advanced, recurrent, or persistent cervical cancer is often incurable. Therefore, in-depth insights into the molecular mechanisms are needed for the development of novel therapeutic targets and the improvement of current therapeutic strategies. In this study, we investigated the role of GLI2 and GLI3 in the regulation of the malignant properties of cervical cancer. We showed that down-regulation of GLI2, but not GLI3, with an inducible GLI2 shRNA inhibited the growth and migration of cervical cancer cell lines, which could be rescued by ectopic expression of GLI2. GLI2 appeared to support cell growth by regulating the mitosis, but not the apoptosis, of the cervical cancer cells. Mechanistically, these functions of GLI2 were in part mediated by the activation of AKT pathway. Knockdown of GLI2, but not GLI3, also inhibited xenograft growth of cervical cancer cells in vivo. Finally, analysis of TCGA data showed that high levels of GLI2, but not GLI3, conferred a poor prognosis in cervical cancer patients. These observations for the first time suggest that GLI2, but not GLI3, exerts a tumor-promoting role in cervical cancer and may be targeted as a novel therapeutic strategy.

Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated with platinum-based chemotherapy.

PURPOSE: DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR has been reported as a prognostic marker in certain cancers; however, the results are controversial. Therefore, identification of the prognostic value of MMR genes in ovarian cancer based on a large sample size is pivotal. METHODS: In the current study, we systemically investigated the prognostic roles of seven MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2, in ovarian cancer patients treated with platinum-based chemotherapy through "The Kaplan-Meier plotter" (KM plotter) database, which contains gene expression data and survival information of ovarian cancer patients. RESULTS: Among seven MMR genes, high mRNA levels of MSH6, MLH1 and PMS2 were significantly associated with a better overall survival for all ovarian cancer patients treated with platinum-based chemotherapy, especially in late-stage and poor-differentiated ovarian cancer patients. Increased MSH6 and PMS2 mRNA expression was correlated with a favorable overall survival in serous ovarian cancer patients. CONCLUSIONS: Our results indicate that sufficient MMR system is associated with an improved survival in ovarian cancer treated with platinum-based chemotherapy. MMR gene may be a potential prognosis predictor in ovarian cancer.

Prognostic values of excision repair cross-complementing genes mRNA expression in ovarian cancer patients.

Excision repair cross-complementing (ERCC) genes, key components of the nucleotide excision repair pathway, are regarded as crucial factors for DNA repair capacity. Previous studies have investigated prognostic values of ERCC genes in a number of malignancies. However, the relationship between ERCC genes and prognosis of ovarian cancer patients remains controversial. Therefore, in the current study, we systematically analyze the prognostic values of ERCC genes in ovarian cancer by the Kaplan-Meier plotter, which includes updated gene expression data and survival information of 1656 ovarian cancer patients. Our results showed that high expression of ERCC1 and ERCC8 mRNA was related to a worse overall survival among ovarian cancer patients, especially in late stage and poor differentiation serous ovarian patients. Increased ERCC4 mRNA expression indicated a better overall survival among serous ovarian cancer patients. The other ERCC genes were uncorrelated with prognosis in ovarian cancer. These results indicate that some ERCC genes have critical prognostic values in ovarian cancer.

Correlation between estrogen receptor expression and prognosis in epithelial ovarian cancer: a meta-analysis.

OBJECTIVE: Accumulated studies have investigated the prognostic significance of estrogen receptor expression in epithelial ovarian cancer, but results remain controversial. The aim of this study was to perform a meta-analysis to clarify the prognostic value of estrogen receptor expression in epithelial ovarian cancer. METHODS: A systematic search was performed in PUBMED, EMBASE, and COCHRANE databases to identify relevant studies up to December 2016. The pooled hazard rates (HR) with 95% confidence intervals (CIs) for overall survival and time to tumor progression were calculated and then weighted and pooled in this meta-analysis with a random-effect model. RESULTS: Thirty-five studies with a total of 5824 patients were included. In brief, the expression of estrogen receptor was associated with an improved overall survival (HR = 0.86, 95% CI = 0.76-0.97), whereas there was no significant difference between estrogen receptor and time to tumor progression among epithelial ovarian cancer patients. Subgroup analysis revealed that estrogen receptor expression was significantly correlated with overall survival in different subgroups, such as in unclassified epithelial ovarian cancer (HR= 0.80, 95% CI = 0.66-0.95), studies using immunohistochemistry detection method (HR= 0.85, 95% CI = 0.73-1.00), European population (HR= 0.75, 95% CI = 0.60-0.94) and estrogen receptor α subtype (HR= 0.78, 95% CI = 0.62-0.98). CONCLUSIONS: Estrogen receptor, especially estrogen receptor α, was associated with an improved overall survival in epithelial ovarian cancer. Estrogen receptor expression may be a promising prognostic factor in epithelial ovarian cancer patients.

Effect of vitamin E supplementation on uterine cervical neoplasm: A meta-analysis of case-control studies.

Several epidemiological studies have suggested that vitamin E could reduce the risk of uterine cervical neoplasm. However, controversial data were presented by different reports. Hence, we conducted a meta-analysis to assess the relationship between vitamin E and the risk of cervical neoplasia. We performed a comprehensive search of the PubMed, Embase and Cochrane databases through December 31, 2016. Based on a fixed-effects or random-effects model, the odds ratio (OR) and 95% confidence intervals (CIs) were calculated to assess the combined risk. Subgroup analyses and meta-regression were done to assess the source of heterogeneity. Subgroup analyses were performed according to survey ways, types of cervical neoplasia, study populations. A protocol was registered with PROSPERO (No. CRD42016036672). In total, 15 case-control studies were included, involving 3741 cases and 6328 controls. Our study suggested that higher category of vitamin E could reduce the cervical neoplasia risk (OR = 0.58, 95% CIs = 0.47-0.72, I2 = 83%). In subgroup-analysis, both vitamin E intake and blood levels of vitamin E had a significant inverse association with the risk of cervical neoplasm. Additionally, we found the same relationship between vitamin E and cervical neoplasia among different populations and types of cervical neoplasia. Meta-regression showed that none of the including covariates were significantly related to the outcomes. No evidence of publication bias was observed. In conclusion, vitamin E intake and blood vitamin E levels were inversely associated with the risk of cervical neoplasia.

The prognostic values of signal transducers activators of transcription family in ovarian cancer.

Signal transducer and activator of transcription (STAT), a family of latent cytoplasmic transcription factors, are composed of seven identified members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). STATs are associated with several biological processes such as cell proliferation, invasion, and metastasis in various cancer types. In addition, the STAT family has been well studied as a prognostic predictor for a considerable number of solid tumors. However, the prognostic value of the STAT family in ovarian cancer patients remains unclear. In our present study, we intend to access the prognostic roles of the STAT family in ovarian carcinoma through the 'Kaplan-Meier plotter' (KM plotter) online database, which collected gene expression data and survival information (overall survival (OS)) from a total of 1582 ovarian cancer patients. Our results show that high mRNA expression of STAT1, STAT4, STAT5a, STAT5b, and STAT6, are correlated to a better OS of ovarian cancer patients, especially the high level of STAT1 and STAT4 are significantly related to a favorable OS for serous ovarian cancer patients. We further accessed the prognostic roles of individual STATs in other clinicopathological features, such as pathological grades, clinical stages, and TP53 mutation, and found that these genes indicate a favorable prognosis especially for late stage, poor differentiation, and TP53 mutated ovarian cancer patients. In conclusion, these results suggest that the STAT family plays a significant prognostic role in ovarian carcinoma and individual STATs, except STAT2 and STAT3, may act as favorable prognostic markers in ovarian cancer.

Prognostic value of progesterone receptor expression in ovarian cancer: a meta-analysis.

OBJECTIVE: While a prognosis value of progesterone receptor (PR) in ovarian cancer has been reported in some publications, controversial data were presented by different reports. In order to address the disagreement of progesterone receptor in ovarian cancer survival, we conducted this meta-analysis. METHODS: Relevant articles on progesterone receptor and ovarian cancer prognosis were identified via a thorough search of PubMed, Embase and Cochrane Central. Hazard ratios (HR) and 95% confidence interval (CI) were extracted from studies on overall survival (OS) and disease-free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS). RESULT: A total of 28 eligible studies containing 5685 patients were collected for analysis. It was found that progesterone receptor positivity was significantly associated with favorable overall survival (OS) (HR = 0.86, 95% CI = 0.78 to 0.95, P = 0.002) and disease-free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS) (HR = 0.75, 95% CI = 0.61 to 0.93, P = 0.008) of ovarian cancer patients. Subgroup analysis showed that progesterone receptor expression was associated with a favorable prognosis of unclassified ovarian cancer, European origin, and immunohistochemical detection method. CONCLUSION: Progesterone receptor expression can be used as a favorable prognostic predictor in ovarian cancer managements.