Alternative ANKHD1 transcript promotes proliferation and inhibits migration in uterine corpus endometrial carcinoma.

Alternative splicing (AS) is common in gene expression, and abnormal splicing often results in several cancers. Overall survival-associated splicing events (OS-SEs) have been used to predict prognosis in cancer. The aim of this study was to investigate the presence and function of OS-SEs in uterine corpus endometrial carcinoma (UCEC). Based on TCGA and TCGASpliceSeq databases, gene expression and the AS data of UCEC samples were retrieved. An alternate terminator of ANKHD1 transcripts named ANKHD1-BP3 was found to be significantly related to metastasis and OS in UCEC and significantly associated with HSPB1. The upregulated expression of HSPB1 induced downregulation of ANKHD1-BP3 and promoted tumor metastasis. These findings indicate that HSPB1, a splicing factor, regulates the expression of ANKHD1-BP3 to promote metastasis in UCEC.

A novel prognostic biomarker CD3G that correlates with the tumor microenvironment in cervical cancer.

Cervical cancer (CESC) is the fourth most common and death-causing gynecological cancer, mostly induced by infection of human papillomavirus (HPV). Multiple components of the tumor microenvironment (TME), such as tumor infiltrating immune cells, could be targets of immunotherapy for HPV-related CESC. However, little is known about the TME of CESC until now. Here, we aimed to uncover the pathogenesis as well as to identify novel biomarkers to predict prognosis and immunotherapy efficacy for CESC. Combining the transcriptomic data and clinical characteristics, we identified differentially expressed genes in CESC samples from TCGA database by comparing the two groups with different ImmuneScore and StromalScore. Next, we detected ten key genes based on the PPI network and survival analyses with the univariate Cox regression model. Thereafter, we focused on CD3G, the only gene exhibiting increased RNA and protein expression in tumors by multiple analyses. Higher CD3G expression was associated with better survival; and it was also significantly associated with immune-related pathways through GSEA analysis. Furthermore, we found that CD3G expression was correlated with 16 types of TICs. Single cell RNA-sequencing data of CD3G in lymphocytes subgroup indicated its possible role in HPV defense. Hence, CD3G might be a novel biomarker in prognosis and immunotherapy for CESC patients.

TPPP3 inhibits the proliferation, invasion and migration of endometrial carcinoma targeted with miR-1827.

OBJECTIVE AND DESIGN: Database screening indicated that tubulin polymerization-promoting protein 3 (TPPP3) was involved in pathogenesis of multiple cancer types. miR-1827 has a potential role in a variety of human cancers. However, the role of TPPP3 and its underlying molecular mechanism in endometrial cancer (EC) has not been investigated. Herein, we aimed to reveal the role of TPPP3/miR-1827 in EC progression. METHODS: Tumour tissue and whole blood samples were collected for the detection of TPPP3 expression. TPPP3 shRNAs and pcDNA-TPPP3 were applied to knockdown or upregulate the TPPP3 expression, and miR-1827 mimic was used to upregulate miR-1827 level. CCK-8 and colony assays were applied to estimate the cell proliferation. Wound healing and Transwell assays were conducted to assess the cell migration and invasion abilities. The dual-luciferase reporter assay was conducted to validate the putative binding site between TPPP3 and miR-1827. Expression of TPPP3, miR-1827 and related proteins in cell lines, tissue and whole blood sample were detected using western blot, RT-qPCR and immunofluorescence. RESULTS: TPPP3 was observed markedly elevated in EC patients and cells. TPPP3 knockdown displayed evident suppression in cell proliferation, migration and invasion in vitro and in vivo. Moreover, we identified TPPP3 as a direct and functional target gene of miR-1827 in EC cells. The miR-1827 induced regulatory effects on EC cells were partially reversed by TPPP3. Additionally, in vivo study confirmed the findings discovered in vitro. CONCLUSION: TPPP3 exerted oncogenic roles in EC progression by sponging miR-1827. This finding might provide potential targets for EC therapy.

Engineering of Neutrophil Membrane Camouflaging Nanoparticles Realizes Targeted Drug Delivery for Amplified Antitumor Therapy.

PURPOSE: Although the neutrophil membrane (NM)-based nanoparticulate delivery system has exhibited rapid advances in tumor targeting stemmed from the inherited instinct, the antitumor effect requires further improvement due to inefficient cellular internalization in the absence of specific interactions between NM-coated nanoparticles and tumor cells. METHODS: Herein, we fabricated drug-paclitaxel loaded NM camouflaging nanoparticles (TNM-PN) modified with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), favorable for the cellular internalization. RESULTS: The results showed that TNM-PN exerted a significant cytotoxicity to tumor cells by TRAIL-mediated endocytosis and strong adhesion to inflamed endothelial cells in vitro. Due to TRAIL modification as well as the adhesive interactions between neutrophil and inflamed tumor vascular endothelial cells, tumors in TNM-PN group exhibited almost 2-fold higher fluorescence intensities than that of NM camouflaging nanoparticles and 3-fold higher than that of bare nanoparticles, respectively. Significant tumor inhibition and survival rates of mice were achieved in TNM-PN group as a consequence of prolonged blood circulations to 48 h and preferential tumor accumulations, which was ascribed to targeting adhesion originated from NM to immune evasion and subsequent excellent cellular internalization. CONCLUSION: The research unveiled a novel strategy of amplifying cellular internalization based on NM coating nanotechnology to boost antitumor efficacy.

Microscopic phase reconstruction of cervical exfoliated cell under partially coherent illumination.

Basic coherent diffraction imaging methods strongly rely on having a highly coherent illumination in order to reconstruct the phase accurately. However, regardless of considering the turbulent transport medium, the instability of the system or the generation mechanism of the light source, partially coherent illumination is more common in real case. In this paper, we proposed an efficient microscopic phase imaging method to study normal and abnormal cervical exfoliated cells. By applying three phase modulations in a single point of the sample's transmitted field, the phase can be retrieved with correspoding three intensities under partially coherent illumination. Compared with intensity map, we can efficiently and clearly judge the proportion of high density shrinking abnormal cells from the phase distributions, which provides a confident analysis and evaluation basis for early medical diagnosis of cervical cancer. This study also has potential applications in noninvasive optical imaging of dynamic biological tissues.

Safety and efficacy of a self-developed Chinese pelvic repair system and Avaulta repair system for the treatment of pelvic organ prolapse in women: A multicenter, prospective, randomized, parallel-group study.

The pelvic organ prolapse (POP) repair systems used in China are imported and expensive. Our aim was to compare the efficacy and safety of a self-developed pelvic floor repair system versus the Avaulta system.This was a multicenter, randomized, parallel-group, noninferiority trial of 132 patients with POP stage ≥II from the Tongji Hospital Affiliated to Tongji University and the General Hospital of Ningxia Medical University enrolled from 02/2014 to 03/2015. The patients were randomized 1:1 to POP repair using the self-developed system or the Avaulta system. Perioperative conditions, POP quantification, pelvic floor impact questionnaire-7, and prolapse quality of life questionnaires, gynecological ultrasound, and postoperative complications were compared. Patients were followed at 1.5, 3, and 6 months.According to the POP quantification scores obtained at 6 months after surgery, the cure rates of the self-developed and Avaulta groups were 98.3% and 100.0%, respectively (P > .999). At 6 months follow-up, the pelvic floor impact questionnaire-7 scores of the self-developed and Avaulta groups were both improved (P < .001 vs baseline), with no between-group difference observed (P = .488). There were no differences between the 2 groups for subjective symptoms of POP (all P > .05). There were no significant differences between the 2 groups regarding complications (all P > .05).The self-developed pelvic reconstruction system is safe and effective for the treatment of POP and improves the patients' quality of life, without difference compared to the Avaulta system.

Effects of Tra2-beta1 on proliferation, apoptosis, and metastasis of hypoxic endometrial carcinoma cell and its correlation with clinicopathological features.

BACKGROUND: This study aims to examine the influence of human transformer-2-beta1 (Tra2-beta1) on endometrial carcinoma (EC) development. The effects of Tra2-beta1 on the proliferation, apoptosis, invasion, and cell cycle of EC cells were also investigated. METHODS: Functional in vitro experiments were performed on Tra2-beta1 knockdown cells and hypoxic model cells. Western blot was used to detect HIF-1a, vascular endothelial growth factor (VEGF), and Tra2-beta1 protein expression; CCK8 assay was used to detect cell proliferation; flow cytometry was used to detect apoptosis and cell cycle, and Transwell assay was used to detect cell invasion ability. Tumor specimens were collected from 128 consecutive patients to detect the expression of Tra2-beta1, and the relationship between and EC and Tra-beta1 were analyzed by clinical pathological data, which included lymph node metastasis, pathological types, histological grade, myometrial invasion, etc. RESULTS: Tra2-beta1 was highly expressed in EC and was associated with clinical pathological features. It was related to the prognosis, and was found to promote proliferation (F=48.3, P<0.001) and migration (P<0.05), and inhibit apoptosis (P<0.05). Statistical analyses revealed a positive correlation between Tra2-beta1 and HIF-1a (correlation coefficient =0.36, P<0.001) and VEGF protein (correlation coefficient =0.23, P=0.021). In the hypoxic cell group and the combined intervention group, cell proliferation after 72 h was 9,783±45.6 and 6,783±68.4 (P<0.001), while the number of invasive cells was 421±16.8 and 276±11.2 (P<0.001), respectively. The apoptosis rates were 0.45±0.03 and 1.28±0.16, respectively (P<0.05). CONCLUSIONS: The present findings demonstrate that the development of EC is positively correlated with Tra2-beta1. Tra2-beta1 may reverse the effect of hypoxia on EC, and this may provide new insights into the occurrence and development of EC.

Expression of TRA2B in endometrial carcinoma and its regulatory roles in endometrial carcinoma cells.

Expression levels of Transformer 2 protein homolog beta (TRA2B) in patients with endometrial carcinoma were assessed to investigate the impact of TRA2B on endometrial carcinoma cells. Furthermore, we analyzed the expression of several genes in the tissue samples from patients with endometrial cancer (EC) to identify whether cancer related genes we chose are differently expressed between the endometrial carcinoma tissues and adjacent normal tissues. The results of RT-qPCR analysis, western blot technology and immunofluorescence method consistently manifested that the expression of several genes in endometrial carcinoma tissue was significantly dysregulated between the two groups. Among the dysregulated genes, the strongly upregulated TRA2B in the tissues and serum from patients with EC was selected for further analysis. Endometrial carcinoma cells were transfected with chemically synthesized TRA2B plasmid, siRNA-TRA2B and their corresponding negative control respectively to assess the effects of TRA2B on the EC cells. Overexpression of TRA2B increased both the cell viability and proliferation potency of EC cells. Whereas, the viability and the proliferation ability of EC cells were strongly decreased by siRNA-TRA2B treatment. Furthermore, the invasion of EC cells was promoted by transfection of TRA2B and overexpression of TRA2B decreased the apoptosis of EC cells. Moreover, siRNA-TRA2B transfection inhibited the invasion but accelerated apoptosis of EC cells. Our results demonstrated that TRA2B is closely related to the development of endometrial carcinoma, and inhibition of TRA2B can decrease viability, proliferation and invasion of endometrial carcinoma, suggesting TRA2B is associated with the pathogenesis of human EC. Knockdown of TRA2B may be used for treatment of endometrial carcinoma, furthermore, these findings suggest an experimental foundation to clinical prognostic role of TRA2B in patients with endometrial carcinoma.

Excellent analytical and clinical performance of a dry self-sampling device for human papillomavirus detection in an urban Chinese referral population.

AIM: To evaluate the analytical and clinical effectiveness of cervicovaginal self-sampling with a dry sampling device (Evalyn Brush) for high-risk human papillomavirus (hr-HPV) testing and detection of cervical disease. METHODS: The study population consisted of 101 patients from a large gynecological outpatient clinic in Shanghai referred for abnormal cervical screening results and 101 women without cervical lesions. Self-samples obtained in the clinic and physician-collected cervical specimens (reference) were stored at -20 °C for 16-18 weeks and then transferred to 20 ml of ThinPrep medium and tested for hr-HPV using a multiplex real time polymerase chain reaction assay. All women had a colposcopic examination with a Pap smear and directed or random biopsies. RESULTS: High risk-HPV was detected in 92 patients (45.5%) with the self-collected cervicovaginal specimens and in 93 (46.0%) with the physician-collected cervical specimens, resulting in an agreement of 97.5% and a Kappa of 0.95 (95% confidence interval 0.91-0.99). Among all of the included women, 46 (22.8%) had cervical intraepithelial neoplasia grade 3 or worse (cervical intraepithelial neoplasia 3+). Hr-HPV was found in 43 of these patients (93.5%) with self-sampling and in 44 (95.7%) with the physician-collected specimens. CONCLUSIONS: Self-collected dry cervicovaginal samples transferred to ThinPrep medium and tested for hr-HPV using a clinically validated polymerase chain reaction assay showed very good agreement with physician-collected cervical specimens and a very high hr-HPV positivity rate for cervical intraepithelial neoplasia 3 +.

MicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial ovarian cancer.

AIM: To evaluate the clinical significance of microRNA (miR)-130b-Runt domain transcription factor (RUNX3) axis and its effects on oncogenic phenotypes of human epithelial ovarian cancer (EOC). METHODS: QRT-PCR was performed to detect the expression of miR-130b and RUNX3 mRNA in 100 EOC and 20 normal ovarian tissues. The associations between miR-130b and/or RUNX3 expression and various clinicopathological features of EOC patients were statistically analyzed. Then, the effects of miR-130b-RUNX3 axis on migration and invasion of EOC cells were assessed in vitro. RESULTS: miR-130b expression was downregulated, while RUNX3 mRNA was upregulated, in EOC tissues compared to normal ovarian tissues (both P=0.001). Importantly, the expression level of miR-130b in EOC tissues was negatively correlated with that of RUNX3 mRNA significantly. Additionally, miR-130b-low and/or RUNX3-high expression were all closely correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage (all P<0.05). Moreover, overexpression of miR-130b reduced the expression of RUNX3 and inhibited cancer cell migration and invasion of EOC cells, whereas knockdown of miR-130b increased the expression of RUNX3 and promoted cancer cell migration and invasion of EOC cells. After that, the impaired motility of the miR-130b overexpression cells was recovered partly by the expression of RUNX3. Furthermore, the knockdown of RUNX3 also gave rise to a decrease in cell migration and invasion. CONCLUSION: Our data reveal that the dysregulation of miR-130b-RUNX3 axis may play important roles in EOC development and progression, and the loss of miR-130b may contribute to the malignant biological behavior of EOC cells via regulating the expression of RUNX3, implying their potentials as promising markers for predicting EOC progression and as candidate targets for gene therapy.

A new surgery for recurrent or persist stress urinary incontinence in females after primary mid-urethral slings.

OBJECTIVE: To retrospectively evaluate the efficacy of a new complementary mid-urethral sling surgery (Tong's hammock anterior, THA) in treatment of recurrent or persist stress urinary incontinence (SUI) in females after primary synthetic mid-urethral slings (MUSs). METHODS: THA was performed in 27 females with recurrent or persist SUI after primary MUSs from June 2005 and July 2010. These patients were followed up for one year, and clinical data including main complaints, operation duration, blood loss, efficacy and complications were reviewed. RESULTS: All 27 SUI patients were treated with THA surgery, a trans-vaginal mid-urethral sling on the descending pubic ramus. The average operation time was 39 min (range: 25-70 min), average blood loss was 70 ml (range: 20-120 ml). After urinary catheter removal, all patients could micturate and their average residual urine was 25.2 ml (range: 0-80 ml). The average hospital stay was 4.7 days (rage: 3-7 days). SUI symptom was persistent in 2 patients after THA surgery and the effective rate reached 92.5%. At 3 months, 6 months and 1 year after surgery, the effective rate was 92.5% (25/27), 92% (23/25) and 87.5% (21/24), respectively. 6 months after THA surgery, 2 were lost to follow up; 1 had recurrent SUI at 1 year and 1 had mesh erosion, 1 died of other diseases, and operative complications were absent after surgery. CONCLUSIONS: THA surgery is an effective method for treating recurrent or persistent SUI after primary MUSs. It is cheap, efficient, and easy to handle.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) and human transformer-2-beta1 (hTra2-beta1)-regulated estrogen receptor-alpha improves prognosis of endometrial cancer.

PURPOSE OF INVESTIGATION: Heterogeneous nuclear ribonucleoprotein (hnRNP) family possesses decreasing effect towards endometrial cancer (EC) and human transformer-2-betal (hTra2-betal) performs an intimate relationship with EC, either. Recent study shows that hnRNPs and hTra2-betal regulate the genetic expression, which is concerned with estrogen receptor (ER). MATERIALS AND METHODS: The present study was designed to investigate the link between ER and hnRNPs or hTra2-betal in the prognosis of EC patients by Real-time PCR and immunohistochemisty (IHC). RESULTS: Results showed that ER protein expression presented a significant change in the recurrence and outcome of EC patients, and the nucleus hTra2-betal protein expression was also increased in the recurrent patients, indicating that the three might be important in ER expression in the prognosis therapy of EC patients. CONCLUSION: The present findings provide an insight of pharmaceutical targeting therapy and prognosis of EC.