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.
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-β (TGF-β) 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.
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,, 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. K E Y W O R D S clinically apparent early stage, malignant ovarian germ cell tumours, omentectomy, prognostic outcomes, propensity score matching, reproductive outcomes
BackgroundSmall 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.MethodsThis 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. ResultsThe 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.ConclusionThe 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.
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