Positive and Negative Impacts of Interfacial Hydrogen Bonds on Photocatalytic Hydrogen Evolution.

Understanding the behavior of water molecules at solid-liquid interfaces is crucial for various applications such as photocatalytic water splitting, a key technology for sustainable fuel production and chemical transformations. Despite extensive studies conducted in the past, the impact of the microscopic structure of interfacial water molecules on photocatalytic reactivity has not been directly examined. In this study, using real-time mass spectrometry and Fourier-transform infrared spectroscopy, we demonstrated the crucial role of hydrogen bond (H-bond) networks on the photocatalytic hydrogen evolution in thickness-controlled water adsorption layers on various TiO2 photocatalysts. Under controlled water vapor environments with relative humidity (RH) below 70%, we observed a monotonic increase in the H2 formation rate with increasing RH, indicating that reactive water molecules were present not only in the first adsorbed layer but also in several overlying layers. In contrast, at RH > 70%, when more than three water layers covered the catalyst surface, the H2 formation rate turned to decrease dramatically because of the structural rearrangement and hardening of the interfacial H-bond network induced during further water adsorption. This unique many-body effect of interfacial water was consistently observed for various TiO2 particles with different crystalline structures, including brookite, anatase, and a mixture of anatase and rutile. Our results demonstrated that depositing several water layers in a water vapor environment with RH ∼ 70% is optimal for photocatalytic hydrogen evolution rather than liquid-phase reaction conditions in aqueous solutions. This study provides molecular-level insights into designing interfacial water conditions to enhance photocatalytic performance.

Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Reactive oxygen species-induced long intergenic noncoding RNA p21 accelerates abdominal aortic aneurysm formation by promoting secretary smooth muscle cell phenotypes.

Whether long noncoding RNAs participate in the formation of abdominal aortic aneurysms (AAAs) through the regulation of SMC phenotypic switching is unknown. lincRNA-p21 induced by reactive oxygen species (ROS) is likely functionally associated with SMC phenotypic switching. We thus investigated the role of lincRNA-p21 in SMC phenotypic switching-associated AAA formation and its underlying mechanisms. An analysis of human and mouse abdominal aortic samples revealed that the lincRNA-p21 levels were significantly higher in AAA tissue. Stimulation with hydrogen peroxide upregulated the expression of lincRNA-p21 in a dose-dependent manner and converted SMCs from a contractile phenotype to a synthetic, proteolytic, and proinflammatory phenotype in vitro. Moreover, lincRNA-p21 promoted fracture of elastic fibres, reconstruction of the vascular wall, and AAA formation in vivo by modulating SMC phenotypic switching in two mouse models of AAA induced by angiotensin II or porcine pancreatic elastase (PPE) perfusion. Using a bioinformatics prediction method and luciferase reporter gene assays, we further proved that lincRNA-p21 sponged miR-204-5p to release the transcriptional activity of Mekk3 and promoted the NF-κB pathway and thereby played a role in the SMC phenotypic switch and AAA formation. The ROS levels were positively correlated with the lincRNA-p21 levels in human and mouse AAA tissues. The knockdown of lincRNA-p21 in a PPE-induced mouse AAA model increased the miR-204-5p levels and reduced the expression of Mekk3, whereas lincRNA-p21 overexpression had the opposite effect. Collectively, the results indicated that ROS-induced lincRNA-p21 sponges miR-204-5p to accelerate synthetic and proinflammatory SMC phenotypes through the Mekk3/NF-κB pathway in AAA formation. Thus, lincRNA-p21 may have therapeutic potential for AAA formation.

Safety and efficacy of liraglutide on reducing visceral and ectopic fat in adults with or without type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). METHODS: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non-T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. RESULTS: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta-analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = -0.72, 95% confidence interval (CI; -1.12, -0.33)], liver fat [SMD = -0.78, 95% CI (-1.24, -0.32)] and body mass index [weighted mean difference = -1.44, 95% CI (-1.95, -0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = -0.74, 95% CI (-1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. CONCLUSIONS: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured.

Circular RNA Cdyl promotes abdominal aortic aneurysm formation by inducing M1 macrophage polarization and M1-type inflammation.

Macrophage polarization plays a crucial role in regulating abdominal aortic aneurysm (AAA) formation. Circular RNAs (circRNAs) are important regulators of macrophage polarization during the development of cardiovascular diseases. How-ever, the roles of circRNAs in regulating AAA formation through modulation of macrophage polarization remain unknown. In the present study, we compared circRNA microarray data under two distinct polarizing conditions (M1 and M2 macrophages) and identified an M1-enriched circRNA, circCdyl. Loss- and gain-of-function assay results demonstrated that circCdyl overexpression accelerated angiotensin II (Ang II)- and calcium chloride (CaCl2)-induced AAA formation by promoting M1 polarization and M1-type inflammation, while circCdyl deficiency showed the opposite effects. RNA pulldown, mass spectrometry analysis, and RNA immunoprecipitation (RIP) assays were conducted to elucidate the underlying mechanisms by which circCdyl regulates AAA formation and showed that circCdyl promotes vascular inflammation and M1 polarization by inhibiting interferon regulatory factor 4 (IRF4) entry into the nucleus, significantly inducing AAA formation. In addition, circCdyl was shown to act as a let-7c sponge, promoting C/EBP-δ expression in macrophages to induce M1 polarization. Our results indicate an important role for circCdyl-mediated macrophage polarization in AAA formation and provide a potent therapeutic target for AAA treatment.

Prognostic value of preoperative soluble interleukin 2 receptor α as a novel immune biomarker in epithelial ovarian cancer.

PURPOSE: Epithelial ovarian cancer (EOC) is regarded as the deadliest gynecological cancer, and the demand for novel noninvasive prognostic biomarkers remains significant. This study aimed to investigate the prognostic value of preoperative blood biomarkers in EOC patients. METHODS: In total, 73 patients who had undergone ovarian mass resection were enrolled. Serum concentration of biomarkers, including soluble interleukin 2 receptor α (sIL-2R), was measured 1-2 weeks before surgery. Independent prognostic factors for progression-free survival (PFS) were investigated with multivariate Cox regression analysis. A prognostic model was subsequently developed and evaluated by discrimination, calibration and clinical net benefit. Furthermore, transcriptome data of 376 EOC cases from The Cancer Genome Atlas (TCGA) were analyzed with ESTIMATE, CIBERSORT and Maftools algorithm to evaluate the correlation of IL2RA expression with tumor immune microenvironment and immunotherapeutic response. RESULTS: High sIL-2R concentration was found to be the only significant prognostic blood biomarker for PFS by multivariate Cox regression analysis in our center. A prognostic nomogram was developed with satisfactory discrimination, calibration and clinical net benefit. In addition, higher IL2RA expression was significantly associated with higher immune scores, activated CD4+ T cells, M2 macrophages and resting dendritic cells in TCGA data. Furthermore, IL2RA expression was closely related to TMB scores. CONCLUSIONS: sIL-2R is a potential prognostic immune biomarker for EOC patients, and a comprehensive prognostic model comprising sIL-2R with satisfactory discrimination and clinical appliance was developed. Therefore, we recommend routine sIL-2R testing in EOC patients.

Genomic and expressional dynamics of ovarian cancer cell lines in PARPi treatment revealed mechanisms of acquired resistance.

BACKGROUND: Patients with epithelial ovarian cancer (EOC) can benefit from poly- (ADP ribose) polymerase inhibitors (PARPi) therapy. However, PARPi resistance has become a challenge in clinical practice, and its mechanism requires further exploration. METHODS: We established three PARPi-resistant cell strains following olaparib exposure. CCK-8, clonogenic survival, transwell, wound healing, cell cycle, RT-qPCR and western blot assays were performed to explore the functional phenotype of the resistant cells. Whole-exome sequencing and RNA-sequencing were performed to identify the altered genes. Stable knockdown and overexpression were used to investigate the role of EP300, an upstream regulator of E-cadherin and epithelial-mesenchymal transition (EMT), in cell lines. We further validated the finding in clinical ovarian cancer samples by immunohistochemistry. RESULTS: We combined public datasets to obtain an integrated PARPi sensitivity profile in EOC cells, which indicated that primary PARPi resistance could not be fully explained by mutations in BRCA1/2 or homologous recombination deficiency related genes. Genomic and transcriptome analyses revealed distinct mechanisms between primary and acquired resistance. Long-term PARPi treatment induced accumulation of de novo single nucleotide variants (SNV), and the complete frame-shift deletion of PARP1 was detected in the A2780 resistant strain. Additionally, the depressed histone acetyltransferase of EP300 could cause resistant phenotype through activated EMT process in vitro, and associated with PARPi-resistance in EOC patients. CONCLUSION: Long-term PARPi treatment led to evolutionary genomic and transcriptional alterations that were associated with acquired resistance, among which depressed EP300 partly contributed to the resistant phenotype.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Feasibility of the "Cuff-Sleeve" Suture Method for Functional Neocervix Reconstruction in Laparoscopic Radical Trachelectomy: A Retrospective Analysis.

STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility of "cuff-sleeve" sutures for reconstructing a functional neocervix in laparoscopic radical trachelectomy (RT). DESIGN: A retrospective analysis of a case series. SETTING: A teaching hospital. PATIENTS: Twenty-five patients who were diagnosed as early-stage cervical cancer from June 2017 to October 2020 in Sun Yat-sen Memorial Hospital. INTERVENTIONS: Laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients successfully underwent the laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction, and no intraoperative complications occurred or conversion to laparotomy was needed. For all patients, approximately 80% of the cervical length was removed. Surgical radicality and negative surgical margins were also confirmed. During a median follow-up time of 29 months (range 8-48 months), no severe postoperative complications were observed. No cervical stenosis or secondary abnormal menstruation was reported. After the removal of the uterine stent 6 months after surgery, the neocervix length was approximately 14 mm (range 10-19 mm) and almost all the neocervixes were restored closely to the original anatomy. Four of 8 patients attempting actively to conceive were successful, and the cervical length of these pregnant patients was greater than or equal to 15 mm in all but one measurement at different gestational age. Three patients were ongoing pregnant, and the other had delivered successfully with a 16- mm cervix at term without cerclage. CONCLUSION: The "cuff-sleeve" suture method in cervicovaginal reconstruction is feasible in laparoscopic RT. This simplified suture technique can provide a functional neocervix to reduce cervical stenosis and incompetence.

Round ligament suspension and vaginal purse-string suture: Newly optimized techniques to prevent tumor spillage in laparoscopic radical trachelectomy for cervical cancer.

AIM: The purpose of this study was to investigate the surgical techniques and clinical feasibility of nonuterine manipulator and enclosed colpotomy to avoid cancer cell spillages in laparoscopic radical trachelectomy (LRT) for patients with early-stage cervical cancer. METHODS: We performed the newly optimized surgical techniques of round ligament suspension and vaginal purse-string suture in LRT in 12 patients with early-stage cervical cancer from May 2019 to October 2020. Surgical information and postoperative results were recorded. RESULTS: All 12 patients successfully underwent LRT with round ligament suspension and vaginal purse-string suture, and no conversion to laparotomy was required. The median operation time was 268.5 min (range 200-320 min), including 5 min of round ligament suspension, and the median blood loss was 20 mL (range 5-50 mL). The median number of pelvic lymph nodes removed was 27 (range 19-35), and median amounts of paracervical tissue was 24 mm (range 21-26 mm) and vaginal tissue was 18 mm (range 16-26 mm). No intraoperative complication or serious postoperative complications were reported. CONCLUSION: Round ligament suspension and vaginal purse-string suture techniques are feasible and effective in LRT. They can replace uterine manipulator and unprotected colpotomy with satisfactory perioperative outcomes.

Squamous cell carcinoma antigen combined with HPV-16 infection in predicting high-grade squamous intraepithelial lesions of the cervix.

An early screening of HPV and the Thinprep Cytology Test (TCT) can effectively prevent cervical cancer. However, patients with high-grade cervical intraepithelial neoplasia usually escape current screening methods and commonly develop cervical cancer. Hence, to identify effective and specific screening methods for high-grade cervical intraepithelial neoplasia is of vital necessity. In this study, 541 patients collected in Sun Yat-Sen hospital from January 2007 to December 2016 were selected. HPV genotype detection and SCC-ag detection were done in these patients. It was found that when serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity of this novel approach to predict high-grade cervical intraepithelial neoplasia could reach to 83.1% and 62.1%, respectively. The result suggested that the combination of serum SCC-ag level and HPV-16 infection could be used as a novel approach for high-grade cervical intraepithelial neoplasia screening.Impact statementWhat is already known on this subject? Patients with a high-grade cervical intraepithelial neoplasia usually escape current screening methods.What do the results of this study add? When serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity to predict high-grade cervical intraepithelial neoplasia could reach to 83.1 and 62.1%, respectively.What are the implications of these findings for clinical practice and/or further research? Combination of serum SCC-ag level and HPV-16 infection could be used to screen high-grade cervical intraepithelial neoplasia.

Severe cervical inflammation and high-grade squamous intraepithelial lesions: a cross-sectional study.

PURPOSE: Inflammation has been reported as a facilitator in cervical oncogenesis, but the correlation between inflammation and cytological abnormality remains uncertain. The aim of this study was to investigate the correlation between inflammation and cytological abnormality. METHODS: ThinPrep cytological test (TCT) was used to detect cervical cytological abnormalities and inflammation degrees of 46,255 women in this prospective cross-sectional study. Histopathological examination was used to define the cervical intraepithelial neoplasia (CIN) in patients with cervical cytological abnormalities. RESULTS: The study revealed that 8.87% (4102/46,255) of TCT results had cytological abnormalities. The 4102 included cases were classified as the case group, including atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Women with negative intraepithelial lesion or malignancy (NILM) were classified as the control group. About 88.83% (3644/4102) of women with cytological abnormalities showed inflammations. The rate of severe inflammation was significantly higher in the case group than the control group (23.86% vs. 2.0%, P = 0.000). Our results also showed that patients with severe inflammation had a significantly increasing incidence of cytological abnormality by 12.598 times and elevated the risk of HSIL by 756.47 times, compared to the inflammation negative group. CONCLUSION: Severe inflammation was positively related to HSIL. Patients with severe cervical inflammation should be given more follow-ups and regular examinations and treated more carefully than those with mild or no inflammation.

ALDH-1-positive cells exhibited a radioresistant phenotype that was enhanced with hypoxia in cervical cancer.

BACKGROUND: We have previously found there was a small subpopulation of cells with cancer stem cell-like phenotype ALDH-1 in cervical cancer. Radiotherapy has been applied in most of the cervical cancer. However,the mechanisms underlying radioresistance still remained elusive. Our study is to explore whether ALDH+ cell promotes radioresistance by hypoxia. METHODS: Cells were respectively cultured in hypoxia and normoxia environment and analyzed for marker stability, and cell cycle distribution. RESULTS: Cell growth, apoptosis, cell cycle, sphere formation were affected by hypoxia. ALDH-1 and CHK2 were upregulated after hypoxia. CONCLUSIONS: Here we show that ALDH-1 positive cells contribute to cervical carcinoma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction of these cells is enriched after radiation in cervical carcinoma.

Prognostic value of different metastatic sites for patients with FIGO stage IVB endometrial cancer after surgery: A SEER database analysis.

OBJECTIVE: This study aimed to investigate the association between different metastatic sites and survival in endometrial cancer (EC) patients with International Federation of Gynecology and Obstetrics (FIGO) stage IVB disease. METHODS: FIGO stage IVB patients with EC were selected from the surveillance, epidemiology, and end results database. Overall survival (OS) and cause-specific survival (CSS) were analyzed with Kaplan-Meier analysis and log-rank tests. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors for OS and CSS. RESULTS: A total of 929 FIGO stage IVB patients with EC were identified. Patients with peritoneum metastasis were associated with significantly better OS and CSS compared to those with organ-specific metastasis (median OS: 29 vs 19 months, P = .005; median CSS: 47 vs 25 months, P < .001). Moreover, the survival superiority of peritoneum metastasis remained significant when organ-specific metastasis was further classified into specific single-organ metastasis. The multivariate analysis also indicated that compared with peritoneum metastasis, bone, brain, and lung metastasis were independent prognostic factors for worse OS. Similarly, distant lymph node, bone, brain, liver, and lung metastasis were associated with worse CSS. CONCLUSION: Metastatic sites affected prognosis in FIGO stage IVB patients with EC. Patients with peritoneum metastasis had significantly better survival outcomes than those with organ-specific metastasis.

Comparison of two types of the triple incision technique in the treatment of patients with locally advanced vulvar cancer.

Objective: In 2012, we proposed and described a modified triple incision technique (MTIT) for vulvar cancer patients with locally advanced disease. The MTIT has undergone a series of modifications, and a modified MTIT (M-MTIT) has been developed. The purpose of this study was to introduce the M-MTIT and compare it with the MTIT. Study design: This was a retrospective cohort study. Fifty-seven vulvar cancer patients with clinical stage T2 (≥ 4 cm) or T3 disease were included. Of these patients, 28 underwent the MTIT and 29 underwent the M-MTIT. Data on surgery-related complications and survival outcomes were compared. Results: Patients who were treated with the M-MTIT developed significantly less surgery-related morbidities than patients treated with the MTIT (24.1% vs. 60.7%, P = 0.005). Wound breakdown was the most common complication in our cohort, which occurred less frequently in the M-MTIT group than in the MTIT group (10.3% vs. 35.7%, P = 0.022). Multivariate logistic regression analysis identified the M-MTIT as an independent predictor of a reduced risk of wound breakdown. The incidence of other complications, including lymphedema, wound infection and cellulitis, was lower in the M-MTIT group than in the MTIT group; however, the differences did not reach statistical significance. The median follow-up time of this study was 33 months. Kaplan-Meier survival graphs did not show significant differences in recurrence-free survival or overall survival between the two groups. Conclusions: The M-MTIT correlates with lower morbidity rates than the MTIT and does not compromise oncological safety. The M-MTIT can be considered a safe and feasible option for vulvar cancer patients with locally advanced disease.

Elevated CA-125 Level and ER-Negative as Prognostic Factors for Ovarian Metastasis in Patients with Endometrial Cancer: A Retrospective Cohort Study.

BACKGROUND The utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis. MATERIAL AND METHODS A retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002-2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated. RESULTS A total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml. CONCLUSIONS The incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.

Growth arrest-specific 5 attenuates cisplatin-induced apoptosis in cervical cancer by regulating STAT3 signaling via miR-21.

Cervical cancer is the most common cause of female cancer-related mortality worldwide. Decreased expression of long noncoding RNA growth arrest-specific 5 (GAS5) is found in human cervical cancer tissues and associated with poor prognosis. However, the studies on associations between GAS5 level and malignant phenotypes, as well as sensitivity to chemotherapeutic drug in cervical cancer cells are limited. In this study, overexpression of GAS5 in cervical cancer cells resulted in prohibited cell proliferation and colony formation, which were promoted by siGAS5. Enhanced GAS5 increased cell percentage in the G0/G1 phase and decreased cells percentage in the S phase, whereas reduced expression did not. The malignant behaviors of cervical cancer cells, manifested by cell migration and invasion, could be weakened by the GAS5 overexpression and enhanced by siGAS5. Furthermore, in cisplatin-induced cell, overexpression of GAS5 reduced cells viability and enhanced apoptosis, whereas in cells transfected with siGAS5, apoptosis eliminated. We have reported the upregulation of microRNA-21 (miR-21) and its oncogenetic roles in cervical cancer previously. In this study, we found the negative relationship between the GAS5 and miR-21. Moreover, the decrease of miR-21 associated proteins phosphorylated STAT3 and E2F3 was seen in GAS5 overexpressed cells, both of which could be increased by siGAS5. The GAS5 deficiency also reduced miR-21 target proteins TIMP3 and PDCD4 expressions. Taken together, the GAS5 expression level is inversely associated with malignancy, but positively associated with sensitivity to cisplatin-induced apoptosis, suggesting that GAS5 could be a biomarker of cisplatin-resistance in clinical therapy of human cervical cancer.

Overexpression of chloride channel-3 (ClC-3) is associated with human cervical carcinoma development and prognosis.

BACKGROUND: Cervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. ClC-3 may be an important promoter for aggressive metastasis of malignant tumors. In this research, we explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis. METHODS: Paraffin-embedded cervical (n = 168) and lymph node (n = 100) tissue specimens were analysed by immunohistochemistry. Fresh human cervical tissue specimens (n = 165) and four human cervical cell lines were tested for ClC-3 mRNA and protein expression levels by quantitative real-time PCR and western blotting. The relationship between the expression levels of ClC-3, the pathological characteristics of the carcinoma, and the clinical prognosis were statistically analysed. RESULTS: In normal and precancerous (LSIL, HSIL) cervical tissues as well as cervical carcinoma tissues, both ClC-3 mRNA and protein expression levels increased significantly (p < 0.05). The expression level of ClC-3 was closely-related to the histological differentiation (p = 0.029), tumour staging (p = 0.016), tumour size (p = 0.039), vascular invasion (p = 0.045), interstitial infiltration depth (p = 0.012), lymphatic metastasis (p = 0.036), and HPV infection (p = 0.022). In an in vitro experiment, ClC-3 mRNA and protein were found to be overexpressed both in the HeLa and SiHa cell lines, but low expression levels were detected in the C-33A and H8 cell lines (p < 0.05). Furthermore, the high expression levels of ClC-3 was significantly correlated to poor survival in cervical carcinoma patients (Log-rank test, p = 0.046). CONCLUSIONS: These data suggest that overexpression of ClC-3 is closely associated with human cervical carcinoma progression and poor prognosis; this suggests that ClC-3 may function as a patent tumour biomarker and a latent therapeutic target for cervical carcinoma patients.

Chloride channel-3 is required for efficient tumour cell migration and invasion in human cervical squamous cell carcinoma.

OBJECTIVE: Chloride channel-3 (ClC-3) plays significant roles in various physiological and physiopathological activities, including cell migration and invasion ability. The purpose of this study was to evaluate whether ClC-3 influences the migration and invasion of cervical squamous cell carcinoma cells and its possible mechanisms. METHODS: Paraffin-embedded cervical tissues, including normal cervical tissues, cervical squamous cell carcinoma (SCC) and homologous paracancerous tissues, were collected. The cervical squamous cell carcinoma and matched paracarcinoma fresh tissues specimens were collected from 49 patients with SCC, and the normal cervical tissues were collected from 45 non-cervical squamous cell carcinoma patients. The human cervical squamous carcinoma cell line SiHa was cultured. ClC-3 expression was assessed by real-time RT-PCR, immunohistochemistry and Western blot, and the expression of phospho-PI3K/Akt/mTOR and matrix metalloproteinase-9 (MMP-9) was detected by Western blot. Small interfering RNA (siRNA) technology was used to knockdown ClC-3 expression. SiHa cell migration and invasion ability were measured using Transwell assays with or without Matrigel-coated membranes. RESULTS: ClC-3 mRNA and protein expression in SCC tissues from cervical squamous cell carcinoma patients was significantly upregulated, and no significant difference was noted between the matched paracarcinoma fresh tissue from the same patients and non-cervical cancer patients. SiHa cell migration and invasion and phospho-PI3K/Akt/mTOR and MMP-9 expression were attenuated by knocking down ClC-3 expression using ClC-3 siRNA. CONCLUSIONS: ClC-3 participates in the processes of SCC cell migration and invasion and regulates MMP-9 expression via the PI3K/Akt/mTOR signaling pathway.

SOX2 regulates radioresistance in cervical cancer via the hedgehog signaling pathway.

OBJECTIVE: Resistance to radiotherapy accounts for most treatment failures in cervical cancer patients who receive radical radiation therapy. To discover the possible mechanism of radioresistance and improve the 5-year survival rate, we focused on how sex-determining region Y-box 2 (SOX2) mediates radioresistance in cervical cancer as well as on the interaction between SOX2 and the hedgehog (Hh) signaling pathway in this study. METHODS: We established the acquired radioresistant subclone cells Hela-RR and Siha-RR. RT-qPCR, Western blot analysis, IHC, clonogenic survival assay, CCK-8 assay, apoptosis analysis, cell cycle analysis and xenograft models were used to explore the relationship between SOX2 expression and radiation resistance and to determine how SOX2 mediates radioresistance in cervical cancer. Furthermore, luciferase reporter and ChIP-PCR assays were utilized to assess the interaction between SOX2 and the Hh signaling pathway. RESULTS: Our research suggested that high expression of SOX2 was responsible for radioresistance in cervical cancer. SOX2 was observed to be closely related to irradiation-induced survival, proliferation, apoptosis, and cell cycle changes. The Hh signaling pathway was found to be activated in Hela-RR and Siha-RR, and the activation changed with SOX2 expression. IHC staining of SOX2 and Gli1 showed a close relationship between SOX2 and the Hh pathway. Luciferase reporter and ChIP-PCR assays demonstrated that SOX2 interacted with the Hh signaling pathway by occupying the HHAT promoter. CONCLUSIONS: SOX2 is a potential therapeutic target of irradiation resistance in cervical cancer. It mediates radioresistance in cervical cancer via the Hh signaling pathway.