Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study.

INTRODUCTION: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. MATERIALS AND METHODS: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. RESULTS: Among 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35-5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49-3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58-2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55-3.13, P = 0.515) for non-endometrioid EC patients. CONCLUSION: LVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.

Impact of histological subtypes on clinical outcome of endocervical adenocarcinoma.

OBJECTIVE: This multicenter study aimed to investigate the disparity in clinical features and prognosis among different histopathologic subtypes of endocervical adenocarcinoma (EA) based on the 2014 World Health Organization (WHO) classification. METHODS: We retrieved and analyzed data from the Chinese Four C Database between 2004 and 2018. 672EA patients with radical hysterectomies from 32 institutions were retrospectively reviewed. Clinicopathologic characteristics, five-year overall survival (OS), and disease-free survival (DFS) were compared based on histological subtypes. RESULTS: The 5-year DFS and OS rates for usual, endometrioid, mucinous, gastric, villoglandular, clear cell/serous/mesonephric EAs were as follows: 81.3 %, 89.1 %, 63.0 %, 35.6 %, 88.6 %, 79.9 %, respectively (P < 0.0001); 87.4 %, 96.6 %, 74.7 %, 34.0 %, 96.7 %, 86.3 %, respectively (P < 0.0001). Gastric- and mucinous-type exhibited a higher frequency of lymph node metastasis, deep stromal invasion, uterine corpus invasion, and recurrence than the usual -type (recurrence rate:50.00 % vs 29.90 % vs 15.50 %, P < 0.0001). Multivariate analysis revealed gastric-type was significantly associated with inferior DFS (HR,3.018; 95 % CI, 1.688-5.397; P < 0.0001) and OS(HR, 4.114; 95 % CI, 2.002-8.453; P < 0.0001). Furthermore, compared to the usual -type, mucinous-type demonstrated significantly worse DFS (HR, 1.773; 95 % CI,1.123-2.8; P = 0.014) and OS (HR, 2.168; 95 % CI,1.214-3.873; P = 0.009) whereas endometrioid-type was an identified as independent factor for better DFS (HR, 0.365; 95 % CI,0.143-0.928; P = 0.034). Villoglandular subtype displayed similar features and favorable prognosis as the usual type. CONCLUSIONS: Relevant clinical features and prognosis varied significantly among histological subtypes of EA, thus offering valuable guidance for the development of subtype-specific treatment strategies to optimize EA management.

Reclassifying BRCA1 c.4358-2A > G and BRCA2 c.475 + 5G > C variants from "Uncertain Significance" to "Pathogenic" based on minigene assays and clinical evidence.

BACKGROUND: Pathogenic variants in BRCA genes play a crucial role in the pathogenesis of ovarian cancer. Intronic variants of uncertain significance (VUS) may contribute to pathogenicity by affecting splicing. Currently, the significance of many intronic variants in BRCA has not been clarified, impacting patient treatment strategies and the management of familial cases. METHOD: A retrospective study was conducted to analyze BRCA intronic VUS in a cohort of 707 unrelated ovarian cancer patients at a single institution from 2018 to 2023. Three splicing predictors were employed to analyze detected intronic VUS. Variants predicted to have splicing alterations were selected for further validation through minigene assays. Patient and familial investigations were conducted to comprehend cancer incidence within pedigrees and the application of poly (ADP-ribose) polymerase inhibitors (PARPi) by the patients. In accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG), the intronic VUS were reclassified based on minigene assay results and clinical evidence. RESULT: Approximately 9.8% (69/707) of patients were identified as carriers of 67 different VUS in BRCA1/2, with four intronic variants accounting for 6% (4/67) of all VUS. Splicing predictors indicated potential splicing alterations in splicing for BRCA1 c.4358-2A>G and BRCA2 c.475+5G>C variants. Minigene assays utilizing the pSPL3 exon trapping vector revealed that these variants induced changes in splicing sites and frameshift, resulting in premature termination of translation (p. Ala1453Glyfs and p. Pro143Glyfs). According to ACMG guidelines, BRCA1 c.4358-2A>G and BRCA2 c.475+5G>C were reclassified as pathogenic variants. Pedigree investigations were conducted on patients with BRCA1 c.4358-2A>G variant, and the detailed utilization of PARPi provided valuable insights into research on PARPi resistance. CONCLUSION: Two intronic VUS were reclassified as pathogenic variants. A precise classification of variants is crucial for the effective treatment and management of both patients and healthy carriers.

RUNX1-IT1 acts as a scaffold of STAT1 and NuRD complex to promote ROS-mediated NF-κB activation and ovarian cancer progression.

Dysregulated expression of long-stranded non-coding RNAs is strongly associated with carcinogenesis. However, the precise mechanisms underlying their involvement in ovarian cancer pathogenesis remain poorly defined. Here, we found that lncRNA RUNX1-IT1 plays a crucial role in the progression of ovarian cancer. Patients with high RUNX1-IT1 expression had shorter survival and poorer outcomes. Notably, knockdown of RUNX1-IT1 suppressed the proliferation, migration and invasion of ovarian cancer cells in vitro, and reduced the formation of peritoneum metastasis in vivo. Mechanistically, RUNX1-IT1 bound to HDAC1, the core component of the NuRD complex, and STAT1, acting as a molecular scaffold of the STAT1 and NuRD complex to regulate intracellular reactive oxygen homeostasis by altering the histone modification status of downstream targets including GPX1. Consequently, RUNX1-IT1 activated NF-κB signaling and altered the biology of ovarian cancer cells. In conclusion, our findings demonstrate that RUNX1-IT1 promotes ovarian malignancy and suggest that targeting RUNX1-IT1 represents a promising therapeutic strategy for ovarian cancer treatment.

NIR-driven photoelectrochemical-fluorescent dual-mode biosensor based on bipedal DNA walker for ultrasensitive detection of microRNA.

Optical biosensors have become powerful tools for bioanalysis, but most of them are limited by optic damage, autofluorescence, as well as poor penetration ability of ultraviolet (UV) and visible (Vis) light. Herein, a near-infrared light (NIR)-driven photoelectrochemical (PEC)-fluorescence (FL) dual-mode biosensor has been proposed for ultrasensitive detection of microRNA (miRNA) based on bipedal DNA walker with cascade amplification. Fueled by toehold-mediated strand displacement (TMSD), the bipedal DNA walker triggered by target miRNA-21 is formed through catalytic hairpin assembly (CHA), which can efficiently move along DNA tracks on CdS nanoparticles (CdS NPs)-modified fluorine doped tin oxide (FTO) electrode, resulting in the introduction of upconversion nanoparticles (UCNPs) on electrode surface. Under 980 nm laser irradiation, the UCNPs serve as the energy donor to emit UV/Vis light and excite CdS NPs to generate photocurrent for PEC detection, while the upconversion luminescence (UCL) at 803 nm is monitored for FL detection. This PEC-FL dual-mode biosensor has achieved the ultrasensitive and accurate analysis of miRNA-21 in human serum and different gynecological cancer cells. Overall, the proposed dual-mode biosensor can not only couple the inherent features of each single-mode biosensor but also provide mutual authentication of testing results, which opens up a new avenue for early diagnosis of miRNA-related diseases in clinic.

Laparoscopic versus open radical hysterectomy in FIGO 2018 early-stage cervical adenocarcinoma: Long-term survival outcomes after propensity score matching.

OBJECTIVE: To compare the long-term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early-stage cervical adenocarcinoma. METHODS: Based on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early-stage cervical adenocarcinoma were retrospectively reviewed. Long-term and short-term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log-rank method in the whole study population and after propensity score matching. RESULTS: There was no difference in disease-free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532-1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526-2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk-adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p < 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p < 0.001) in risk-adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613). CONCLUSIONS: LRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early-stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.

Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis.

Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.

Which factors predict parametrial involvement in stage IB cervical cancer? A Chinese multicentre study.

OBJECTIVE: To explore the clinicopathological risk factors influencing parametrial involvement (PI) in stage IB cervical cancer patients and compare the oncological outcomes between Q-M type B radical hysterectomy (RH) group and Q-M type C RH group. METHODS: Univariate and multivariate analyses were performed to explore the clinicopathological factors related to PI. Overall survival (OS) and disease-free survival (DFS) in patients with stage IB cervical cancer who underwent Q-M type B or Q-M type C RH under different circumstances of PI were also compared before and after propensity score matching (1:1 matching). RESULTS: A total of 6358 patients were enrolled in this study. Depth of stromal invasion>1/2 (HR: 3.139, 95% CI: 1.550-6.360; P = 0.001), vaginal margin (+) (HR: 4.271, 95% CI: 1.368-13.156; P = 0.011), lymphovascular space invasion (LVSI) (+) (HR: 2.238, 95% CI: 1.353-3.701; P = 0.002) and lymph node metastases (HR: 5.173, 95% CI: 3.091-8.658; P < 0.001) were associated with PI. Among the 6273 patients with negative PI, those in the Q-M type B RH group had a higher 5-year OS and DFS than those in the Q-M type C RH group before and after 1:1 matching. Among the 85 patients with positive PI, Q-M type C RH showed no survival benefits before and after 1:1 matching. CONCLUSION: Stage IB cervical cancer patients with no lymph node metastasis, LVSI(-) and depth of stromal invasion ≤1/2 may be considered for Q-M type B radical hysterectomy.

Targeting ovarian cancer stem cells: a new way out.

Ovarian cancer (OC) is the most lethal gynecological malignancy due to tumor heterogeneity, the lack of reliable early diagnosis methods and the high incidence of chemoresistant recurrent disease. Although there are developments in chemotherapies and surgical techniques to improve the overall survival of OC patients, the 5-year survival of advanced OC patients is still low. To improve the prognosis of OC patients, it is important to search for novel therapeutic approaches. Cancer stem cells (CSCs) are a subpopulation of tumor cells that participate in tumor growth, metastasis and chemoresistance. It is important to study the role of CSCs in a highly heterogeneous disease such as OC, which may be significant to a better understanding of the oncogenetic and metastatic pathways of the disease and to develop novel strategies against its progression and platinum resistance. Here, we summarized the current findings about targeting methods against ovarian cancer stem cells, including related signaling pathways, markers and drugs, to better manage OC patients using CSC-based therapeutic strategies.

Assessment of prognostic and reproductive outcomes of omentectomy for patients with clinically apparent early-stage (I, II) malignant ovarian germ cell tumours: A multicentre retrospective study.

OBJECTIVE: This study assessed the effect of omentectomy on the prognosis and fertility in patients with clinically early-stage (I, II) malignant ovarian germ cell tumours (MOGCT). DESIGN: A retrospective multicentre study. SETTING: Four university teaching hospitals in China. POPULATION: A total of 268 patients with clinically apparent early-stage (I, II) MOGCT. METHODS: Data were obtained from the medical records. Additionally, the propensity score matching (PSM) algorithm was adopted. MAIN OUTCOME MEASURES: Prognostic outcomes were disease-free survival (DFS) and overall survival (OS). Fertility outcomes were pregnancy and live birth rates. RESULTS: A total of 187 (69.8%) patients underwent omentectomy. Kaplan-Meier analysis showed no significant differences in DFS and OS between the omentectomy and non-omentectomy groups before and after PSM (p > 0.05). Additionally, subgroup analysis stratified by age (<18 and ≥18 years) showed similar results. International Federation of Gynecology and Obstetrics (FIGO) stage was the only risk factor associated with DFS (hazard ratio [HR] 14.71, 95% confidence interval [CI] 4.47-48.38, p < 0.001) and OS (HR 37.36, 95% CI 3.87-361.16, p = 0.002). Pregnancy and live birth rates in the total population were 80.3% and 66.7%, respectively. There were no significant differences between the two groups before and after PSM. CONCLUSIONS: Omentectomy did not improve survival or affect fertility in patients with clinically apparent early-stage (I, II) MOGCT, regardless of the age. The clinical FIGO stage was an independent risk factor for recurrence and death.

Synergistic effects of sodium butyrate and cisplatin against cervical carcinoma in vitro and in vivo.

Backgrounds: Cisplatin-based chemotherapy has been considered as the pivotal option for treating cervical cancer. However, some patients may present a poor prognosis due to resistance to chemotherapy. As a metabolite of natural products, sodium butyrate (NaB) could inhibit the proliferation of several malignant cells, but little is known about its combination with cisplatin in the treatment of cervical cancer. Materials and methods: Flow cytometry, CCK-8 assay, and Transwell assay were utilized to analyze the cellular apoptosis, viability, cellular migration and invasion upon treating with NaB and/or cisplatin. The allograft mice model was established, followed by evaluating the tumor volume and necrotic area in mice treated with NaB and/or cisplatin. Western blot was performed for detecting protein expression involved in epithelial-mesenchymal transition (EMT) and the expression of MMPs. Immunohistochemical staining was conducted with the tumor sections. The transcription, expression, and cellular translocation of ß-catenin were determined using luciferase reporter gene assay, Real-Time PCR, Western blot, and confocal laser scanning microscope, respectively. Results: NaB combined with cisplatin inhibited cell viability by promoting apoptosis of cervical cancer cells. In vivo experiments indicated that NaB combined with cisplatin could inhibit tumor growth and induce cancer cell necrosis. Single application of NaB activated the Wnt signaling pathway and induced partial EMT. NaB alone up-regulated MMP2, MMP7 and MMP9 expression, and promoted the migration and invasion of cervical cancer cells. The combination of cisplatin and NaB inhibited cellular migration and invasion by abrogating the nuclear transition of ß-catenin, reverse EMT and down-regulate MMP2, MMP7 and MMP9. Immunohistochemical staining indicated that NaB combined with cisplatin up-regulated the expression of E-cadherin and reverse the EMT phenotype in the mice model. Conclusions: NaB serves as a sensitizer for cisplatin, which may be a promising treatment regimen for cervical cancer when combined both. NaB alone should be utilized with caution for treating cervical cancer as it may promote the invasion and migration of cervical cancer cells.

Performance of human papillomavirus E6/E7 mRNA assay for primary cervical cancer screening and triage: Population-based screening in China.

Objective: Cervical cancer screening is very important in the prevention and treatment of cervical cancer. In China, the cervical screening strategy needs to be improved. To explore a suitable cervical screening strategy in China, we evaluated the performance of the human papillomavirus (HPV) E6/E7 mRNA (Aptima HPV (AHPV)) assay in primary screening and different triage strategies for women undergoing routine cervical screening. Methods: A total of 10,002 women aged 35 to 65 years of age were recruited in Liaoning Province and Qingdao City, China. Specimens were tested by liquid-based cytology (LBC) and the AHPV assay, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all high-risk HPV (HR-HPV)-positive samples. Test characteristics were calculated based on histological review. Results: We identified 109 women with high-grade squamous intraepithelial lesion or worse (HSIL+), including six with cervical cancer. The sensitivity of AHPV was clearly higher than that of LBC (92.7 [95% CI: 87.2, 97.2] vs. 67.9 [95% CI: 59.6, 76.1], p < 0.001). The specificity of AHPV was 93.0 (95% CI: 92.5, 93.5), which was lower than that of LBC (95.2 [95% CI: 94.8, 95.6], p < 0.001). There was no statistical difference between the positive predictive value of AHPV and LBC (13.5 [95% CI: 11.2, 16.2] vs. 14.3 [95% CI: 11.4, 17.6], p = 0.695). The difference of area under the curve (AUC) values between the AHPV test (0.928 [95% CI: 0.904, 0.953]) and LBC test (0.815 [95% CI: 0.771, 0.860]) in detecting HSIL+ was statistically significant (p < 0.001). Finally, among the three triage strategies, both the sensitivity (73.4 [95% CI: 65.1, 81.7]) and AUC (0.851 [95% CI: 0.809, 0.892]) of AHPV genotyping with reflex LBC triage were the greatest. Conclusion: In summary, the AHPV assay is both specific and sensitive for detecting HSIL+ and may be suitable for use in primary cervical cancer screening in China. AHPV genotyping with reflex LBC triage may be a feasible triage strategy.

BCHE as a Prognostic Biomarker in Endometrial Cancer and Its Correlation with Immunity.

Background: In developed countries, the most common gynecologic malignancy is endometrial carcinoma (EC), making the identification of EC biomarkers extremely essential. As a natural enzyme, butyrylcholinesterase (BCHE) is found in hepatocytes and plasma. There is a strong correlation between BCHE gene mutations and cancers and other diseases. The aim of this study was to analyze the role of BCHE in patients with EC. Methods: A variety of analyses were conducted on The Cancer Genome Atlas (TCGA) data, including differential expression analysis, enrichment analysis, immunity, clinicopathology, and survival analysis. The Gene Expression Omnibus (GEO) database was used to validate outcomes. Using R tools, Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analyses revealed the potential mechanisms of BCHE in EC. Sangerbox tools were used to delve into the relations between BCHE expression and tumor microenvironment, including microsatellite instability (MSI), tumor neoantigen count (TNC), and tumor mutation burden (TMB). BCHE's genetic alteration analysis was conducted by cBioPortal. In addition, the Human Protein Atlas (HPA) was used to validate the outcomes by immunohistochemistry, and an analysis of the protein-protein interaction network (PPI) was performed with the help of the STRING database. Results: Based on our results, BCHE was a significant independent prognostic factor for patients with EC. The prognosis with EC was affected by age, stage, grade, histological type, and BCHE. GSEA showed that BCHE was closely related to pathways regulating immune response, including transforming growth factor-ß (TGF-ß) signaling pathways and cancer immunotherapy through PD1 blockade pathways. The immune analysis revealed that CD4+ regulatory T cells (Tregs) were negatively correlated with BCHE expression and the immune checkpoint molecules CD28, ADORA2A, BTNL2, and TNFRSF18 were all significantly related to BCHE. BCHE expression was also associated with TMB by genetic alteration analysis. Conclusions: Identifying BCHE as a biomarker for EC might help predict its prognosis and could have important implications for immunotherapy.

Comparison of survival outcomes between squamous cell carcinoma and adenocarcinoma/adenosquamous carcinoma of the cervix after radical radiotherapy and chemotherapy.

BACKGROUND: This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy. METHODS: Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China. RESULTS: Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001). CONCLUSIONS: For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC.

Neoadjuvant Chemotherapy Followed by Surgery Versus Abdominal Radical Hysterectomy Alone for Oncological Outcomes of Stage IB3 Cervical Cancer-A Propensity Score Matching Analysis.

OBJECTIVE: To compare the 5-year overall survival (OS) and disease-free survival (DFS) of patients with cervical cancer who received neoadjuvant chemotherapy followed by surgery (NACT) with those who received abdominal radical hysterectomy alone (ARH). METHODS: We retrospectively compared the oncological outcomes of 1410 patients with stage IB3 cervical cancer who received NACT (n=583) or ARH (n=827). The patients in the NACT group were divided into an NACT-sensitive group and an NACT-insensitive group according to their response to chemotherapy. RESULTS: The 5-year oncological outcomes were significantly better in the NACT group than in the ARH group (OS: 96.2% vs. 91.2%, respectively, p=0.002; DFS: 92.2% vs. 87.5%, respectively, p=0.016). Cox multivariate analysis suggested that NACT was independently associated with a better 5-year OS (HR=0.496; 95% CI, 0.281-0.875; p=0.015), but it was not an independent factor for 5-year DFS (HR=0.760; 95% CI, 0.505-1.145; p=0.189). After matching, the 5-year oncological outcomes of the NACT group were better than those of the ARH group. Cox multivariate analysis suggested that NACT was still an independent protective factor for 5-year OS (HR=0.503; 95% CI, 0.275-0.918; p=0.025). The proportion of patients in the NACT group who received postoperative radiotherapy was significantly lower than that in the ARH group (p<0.001). Compared to the ARH group, the NACT-sensitive group had similar results as the NACT group. The NACT-insensitive group and the ARH group had similar 5-year oncological outcomes and proportions of patients receiving postoperative radiotherapy. CONCLUSION: Among patients with stage IB3 cervical cancer, NACT improved 5-year OS and was associated with a reduction in the proportion of patients receiving postoperative radiotherapy. These findings suggest that patients with stage IB3 cervical cancer, especially those who are sensitive to chemotherapy, might consider NACT followed by surgery.

Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs.

BACKGROUND: Small interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma. METHODS: This strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded "AND" gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. RESULTS: The proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs. CONCLUSIONS: The endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.

Serum Levels of S100A11 and MMP-9 in Patients with Epithelial Ovarian Cancer and Their Clinical Significance.

OBJECTIVE: To investigate the serum levels of calgizzarin (S100A11) and matrix metalloproteinase-9 (MMP9) in patients with epithelial ovarian cancer (EOC) and determine their clinical significance. METHODS: Serum levels of S100A11 and MMP9 were detected in patients with EOC, patients with benign ovarian tumor, and healthy women. The correlation between the two markers and clinicopathological characteristics of ovarian cancer was analysed. RESULTS: The serum levels of S100A11 and MMP-9 in patients with EOC were higher than those in patients with benign ovarian tumor and in healthy women, and the expression levels of S100A11 and MMP-9 were positively correlated. S100A11 and MMP-9 were correlated with tumor staging, postoperative residual foci, ascites volume, serum CA125 level, chemotherapy response, and lymph node metastasis, while S100A11 and MMP-9 were not associated with the bilevel classification, histological type, age, and degree of differentiation. CONCLUSION: S100A11 and MMP-9 were both highly expressed in the serum of patients with EOC and were associated with cancer development, invasion, and metastasis. Therefore, they can be used as an important reference maker in the diagnosis and treatment of ovarian cancer.

Clinical analysis of 12 cases of ovarian cystic mature teratoma with malignant transformation into squamous cell carcinoma.

OBJECTIVE: This study aimed to examine the clinicopathological characteristics, treatment, and prognostic factors in 12 cases of malignant transformation of mature cystic teratoma of the ovary (MCTO). METHODS: We performed a retrospective study of 12 patients with malignant transformation of MCTO who were admitted to the Affiliated Hospital of Qingdao University from 2003 to 2019. We examined case records, clinical parameters, and biological assessments. RESULTS: The median age of the patients was 56.5 years and seven of them were postmenopausal. The average tumor size was 18.5 cm. All patients had pelvic masses at their first hospital visit. Nine of the patients had discomfort in the lower abdomen, two presented with a lower abdominal palpable mass, and three were complicated by fever. The median follow-up time was 73 months (12‒193 months). Ten patients survived with a disease-free status and two died. CONCLUSIONS: There is a low incidence of malignant transformation of MCTO, and its most common histological type is squamous cell carcinoma. Age and tumor size are important factors in malignant transformation of teratomas. While there is a lack of treatment guidelines for malignant transformation of MCTO, early diagnosis and treatment may be beneficial for these patients.

Sagittaria trifolia tuber: bioconstituents, processing, products, and health benefits.

Sagittaria trifolia is an aquatic plant that is distributed worldwide. The edible tuber part of S. trifolia is a very common and popular vegetable in China. The aim of the present review is to discuss the discovery of nutraceuticals from S. trifolia tuber by reviewing its major constituents, food processing, food products, and health-promoting benefits. Sagittaria trifolia tuber comprises a series of nutritional and bioactive constituents, including dietary fibers, amino acids, minerals, starches, non-starch polysaccharides, diterpenoids, colchicine, phenols, and organic acids. Food processing affects its flavor, biocomponents, and bioactivity. Numerous S. trifolia tuber-based food products and nutraceuticals have been developed, but new categories of products and the anticipated functions still need to be explored. The non-starch polysaccharides could be the central ingredients that contribute to the plant's antioxidant, hepatoprotective, hypoglycemic, lipid-regulating, and immunostimulatory properties. Of these, antioxidant and hepatoprotective effects have been thoroughly investigated. Procedures for the extraction and purification of polysaccharides influence their health-promoting actions. Overall, S. trifolia tuber is an underutilized aquatic vegetable species that is an emerging subject for nutraceutical research. © 2020 Society of Chemical Industry.