Advances in understanding the molecular mechanisms of borderline ovarian tumors.

Borderline ovarian tumors (BOTs), which are a special type of epithelial tumor of the ovary, lie between benign and malignant tumors and have low malignant potential. Due to the fact that the early symptoms of these tumors are relatively subtle, they are not easy to diagnose clinically. This study explores advancements in clinical detection methods and provides a comprehensive overview of molecules such as cell migration factors, cell transcription factors, cell damage repair factors, cell cycle regulators, and tumor suppressor genes that are related to the development of BOTs and their related mechanisms in recent years, thus aiming to provide more sensitive, specific, and efficient differential diagnosis and treatment plans for patients to improve their prognosis and survival outcomes.

Corrigendum: The research progress on radiation resistance of cervical cancer.

[This corrects the article DOI: 10.3389/fonc.2024.1380448.].

Identification of an inflammatory response-related gene prognostic signature and immune microenvironment for cervical cancer.

Background: Cervical cancer (CC) is the fourth most common cancer among women worldwide. As part of the brisk cross-talk between the host and the tumor, prognosis can be affected through inflammatory responses or the tumor microenvironment. However, further exploration of the inflammatory response-related genes that have prognostic value, microenvironment infiltration, and chemotherapeutic therapies in CC is needed. Methods: The clinical data and mRNA expression profiles of CC patients were downloaded from a public database for this study. In the TCGA cohort, a multigene prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) and Cox analyses. CC patients from the GEO cohort were used for validation. K‒M analysis was used to compare overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors of OS. The immune cell infiltration and immune-related functional score were calculated by single-sample gene set enrichment analysis (GSEA). Immunohistochemistry was utilized to validate the protein expression of prognostic genes in CC tissues. Results: A genetic signature model associated with the inflammatory response was built by LASSO Cox regression analysis. Patients in the high-risk group had a significantly lower OS rate. The predictive ability of the prognostic genes was evaluated by means of receiver operating characteristic (ROC) curve analysis. The risk score was confirmed to be an independent predictor of OS by univariate and multivariate Cox analyses. The immune status differed between the high-risk and low-risk groups, and the cancer-related pathways were enriched in the high-risk group according to functional analysis. The risk score was significantly related to tumor stage and immune infiltration type. The expression levels of five prognostic genes (LCK, GCH1, TNFRSF9, ITGA5, and SLC7A1) were positively related to sensitivity to antitumor drugs. Additionally, the expression of prognostic genes was significantly different between CC tissues and myoma patient cervix (non-tumorous) tissues in the separate sample cohort. Conclusion: A model consisting of 5 inflammation-related genes can be used to predict prognosis and influence immune status in CC patients. Furthermore, the inhibition or enhancement of these genes may become a novel alternative therapy.

The research progress on radiation resistance of cervical cancer.

Cervical carcinoma is the most prevalent gynecology malignant tumor and ranks as the fourth most common cancer worldwide, thus posing a significant threat to the lives and health of women. Advanced and early-stage cervical carcinoma patients with high-risk factors require adjuvant treatment following surgery, with radiotherapy being the primary approach. However, the tolerance of cervical cancer to radiotherapy has become a major obstacle in its treatment. Recent studies have demonstrated that radiation resistance in cervical cancer is closely associated with DNA damage repair pathways, the tumor microenvironment, tumor stem cells, hypoxia, cell cycle arrest, and epigenetic mechanisms, among other factors. The development of tumor radiation resistance involves complex interactions between multiple genes, pathways, and mechanisms, wherein each factor interacts through one or more signaling pathways. This paper provides an overview of research progress on an understanding of the mechanism underlying radiation resistance in cervical cancer.

A novel immune-related risk-scoring system associated with the prognosis and response of cervical cancer patients treated with radiation therapy.

Objective: The tumor microenvironment plays a critical role in the radiotherapy and immunotherapy response of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Radioresistance is a key factor in treatment failure among patients who receive radical radiotherapy. Thus, new immune-related biomarkers associated with radiotherapy response in CESC are needed. Methods: In this study, the CIBERSORT and ESTIMATE methods were applied to determine the percentage of tumor-infiltrating cells and the number of immune components in 103 CESCs treated with radiotherapy from The Cancer Genome Atlas (TCGA) database. The main dysregulated genes were subjected to multivariate and univariate analyses. The prognostic value of this system was studied via receiver operating characteristic curve and survival analysis. For further confirmation, the biomarkers' expression levels and predictive value were validated by immunohistochemistry (IHC) and qRT-PCR. The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in cervical cancer patients treated with radiation therapy. Results: Data for 17 radioresistant and 86 radiosensitive tumors were obtained from the The Cancer Genome Atlas database. 53 immune-related DEGs were identified. GO and KEGG analyses revealed that the DEGs were enriched in protein kinase B signaling, growth factors in cytokines, the MAPK pathway and the PI3K-Akt pathway. Then, 14 key immune-related genes built a risk scoring model were deemed prognostic in CESC with radiotherapy. The area under the curve (AUC) of the model was 0.723, and the high-risk group presented worse outcomes than the low-risk group. In addition, the high-risk group tended to have persistent tumors (p = 0.001). The high expression of WT1 and SPOUYT4 were associated with relapse, the high expression of Angiotensinogen and MIEN1 were associated with nonrelapse. Analysis of the immune microenvironment indicated that M0 macrophages, M2 macrophages, activated mast cells and resting memory CD4+ T cells were positively correlated with the risk score (p < 0.05). Conclusion: The novel immune-related risk scoring system has some advantages in predicting the prognosis and treatment response of cervical cancer patients treated with radiotherapy. Moreover, it might provide novel clues for providing targeted immune therapy to these patients.

Association of the LEP gene with immune infiltration as a diagnostic biomarker in preeclampsia.

Objective: Preeclampsia (PE) is a serious condition in pregnant women and hence an important topic in obstetrics. The current research aimed to recognize the potential and significant immune-related diagnostic biomarkers for PE. Methods: From the Gene Expression Omnibus (GEO) data sets, three public gene expression profiles (GSE24129, GSE54618, and GSE60438) from the placental samples of PE and normotensive pregnancy were downloaded. Differentially expressed genes (DEGs) were selected and determined among 73 PE and 85 normotensive control pregnancy samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). The candidate biomarkers were identified by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analysis. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic ability. For further confirmation, the expression levels and diagnostic value of biomarkers in PE were verified in the GSE75010 data set (80 PE and 77 controls) and validated by qRT-RCR, Western blot, and immunohistochemistry (IHC). The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in PE. Results: In total, 15 DEGs were recognized. The GO and KEGG analyses revealed that the DEGs were enriched in the steroid metabolic process, receptor ligand activity, GnRH secretion, and neuroactive ligand-receptor interaction. The recognized DEGs were primarily implicated in cell-type benign neoplasm, kidney failure, infertility, and PE. Gene sets related to hormone activity, glycosylation, multicellular organism process, and response to BMP were activated in PE. The LEP gene was distinguished as a diagnostic biomarker of PE (AUC = 0.712) and further certified in the GSE75010 data set (AUC = 0.850). The high expression of LEP was associated with PE in clinical samples. In addition, the analysis of the immune microenvironment showed that gamma delta T cells, memory B cells, M0 macrophages, and regulatory T cells were positively correlated with LEP expression (P < 0.05). Conclusion: LEP expression can be considered to be a diagnostic biomarker of PE and can offer a novel perspective for future studies regarding the occurrence and molecular mechanisms of PE.

DPP6 and MFAP5 are associated with immune infiltration as diagnostic biomarkers in distinguishing uterine leiomyosarcoma from leiomyoma.

Objective: Uterine leiomyosarcoma (ULMS) is the most common subtype of uterine sarcoma and is difficult to discern from uterine leiomyoma (ULM) preoperatively. The aim of the study was to determine the potential and significance of immune-related diagnostic biomarkers in distinguishing ULMS from ULM. Methods: Two public gene expression profiles (GSE36610 and GSE64763) from the GEO datasets containing ULMS and ULM samples were downloaded. Differentially expressed genes (DEGs) were selected and determined among 37 ULMS and 25 ULM control samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Disease Ontology (DO) enrichment analyses as well as gene set enrichment analysis (GSEA). The candidate biomarkers were identified by least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic ability. For further confirmation, the biomarker expression levels and diagnostic value in ULMS were verified in the GSE9511 and GSE68295 datasets (12 ULMS and 10 ULM), and validated by immunohistochemistry (IHC). The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in ULMS. Result: In total, 55 DEGs were recognized via GO analysis, and KEGG analyses revealed that the DEGs were enriched in nuclear division, and cell cycle. The recognized DEGs were primarily implicated in non-small cell lung carcinoma and breast carcinoma. Gene sets related to the cell cycle and DNA replication were activated in ULMS. DPP6 and MFAP5 were distinguished as diagnostic biomarkers of ULMS (AUC = 0.957, AUC = 0.899, respectively), and they were verified in the GSE9511 and GSE68295 datasets (AUC = 0.983, AUC = 0.942, respectively). The low expression of DPP6 and MFAP5 were associated with ULMS. In addition, the analysis of the immune microenvironment indicated that resting mast cells were positively correlated with DPP6 and MFAP5 expression and that eosinophils and M0 macrophages were negatively correlated with DPP6 expression (P<0.05). Conclusion: These findings indicated that DPP6 and MFAP5 are diagnostic biomarkers of ULMS, thereby offering a novel perspective for future studies on the occurrence, function and molecular mechanisms of ULMS.

Combination of Estrogen Receptor Alpha and Histological Type Helps to Predict Lymph Node Metastasis in Patients with Stage IA2 to IIA2 Cervical Cancer.

OBJECTIVE: This study aimed to identify a subset of patients with stage IA2 to IIA2 cervical cancer who are at low risk of lymph node metastasis (LNM) using pathological parameters including estrogen receptor alpha (ERα) and progesterone receptor (PR). METHODS: The clinical data of patients with stage IA2 to IIA2 cervical cancer who underwent radical surgery between 2014 and 2015 were retrospectively reviewed. Immunohistochemical staining was used to determine the expression of ERα and PR. A low-risk criterion for LNM was identified using logistic regression analysis, and its performance was estimated through receiver-operating characteristic curve analysis. RESULTS: Of 263 patients, 57 (21.7%) had pathological LNM. ERα (adjusted odds ratio [aOR], 7.582; 95% confidence interval [CI], 2.991-19.222; P < 0.001) and squamous cell carcinoma (aOR, 3.520; 95% CI, 1.887-6.568; P < 0.001) were identified as independent predictors for no LNM by multivariate logistic regression analysis, while PR had no effect on LNM. The rate of LNM was 1.4% for low-risk patients (n = 73) identified as ERα positive with squamous cell carcinoma. The 5-year disease-free survival in low-risk patients was significantly greater than in those negative for ERα and/or those with non-squamous cell carcinoma (96.9% vs 80.1%, P = 0.002). CONCLUSION: ERα positivity and squamous cell carcinoma are associated with a low risk of LNM in patients with stage IA2 to IIA2 cervical cancer. Hence, those patients without a low risk of LNM could be considered for definitive chemoradiotherapy to avoid unnecessary surgery.

Identification of Core Genes Shared by Endometrial Cancer and Ovarian Cancer Using an Integrated Approach.

Ovarian cancer (OC) is one of the most commonly diagnosed cancers among women. Moreover, Endometrial cancer (EC) is a usual genital tract cancer in females; however, the hub genes and molecular pathways shared by these two cancers have not been surveyed yet. So, this study aimed to identify the common candidate genes or biomarkers and molecular pathways in OC and EC. Differences in the expressed genes between these two microarray data sets were detected. Pathway enrichment analysis and gene ontology (GO) was also performed and protein-protein interactions (PPI) network analysis was done using Cytoscape and the most important genes were identified by the Cytohubba plugin. We found that 154 common DEGs shared by OC and EC were also detected. 10 hub proteins were identified as follows: CDC20, BUB1, CENPF, KIF11, CCNB2, FOXM1, TTK, TOP2A, DEPDC1, and NCAPG. The most important and significant miRNAs were identified to be hsa-mir-186-5p, hsa-mir-192-5p, hsa-mir-215-5p, and hsa-mir-193b-3p regulated expressions of the DEGs.  This investigation demonstrated that these hub genes and their miRNA might be key genes with great effects on OC and EC. However, more studies are needed for a better understanding of the role of these hub genes and their function in these two cancers.

Long non-coding RNA GClnc1 knockdown suppresses progression of epithelial ovarian cancer by recruiting FOXC2 to disrupt the NOTCH1/NF-κB/Snail pathway.

PURPOSE: Epithelial ovarian cancer (EOC) is a highly fatal gynecological cancer. A long noncoding RNA (lncRNA) gastric cancer-associated lncRNA1 (GClnc1) has been revealed to play critical roles in metastasis. Therefore, the present study aims to explore the correlation between GClnc1 and the metastasis and progression of EOC. METHODS: First, 57 paired EOC and paracancerous tissues were collected to detect GClnc1 expression by RT-qPCR. Subsequently, OVC1 and SKOV3 cells with GClnc1 silencing/overexpression were developed to detect changes in cell activity, apoptosis, migration and invasion abilities. Then, the subcellular localization of GClnc1 was detected by nuclear/cytoplasmic fractionation, ISH and FISH assays. The binding relationships between GClnc1 and forkhead box protein C2 (FOXC2), and between FOXC2 and NOTCH1 were predicted and verified. RESULTS: GClnc1 was significantly overexpressed in EOC tissues, and knockdown of GClnc1 inhibited cell viability and promoted apoptosis. Moreover, GClnc1 in the nucleus bound to the transcription factor FOXC2, thereby activating the transcription of NOTCH1. NOTCH1 overexpression enhanced the proliferation and epithelial-mesenchymal transition of SKOV3 and OVC1 cells. Moreover, NOTCH1 activated the NF-κB/Snail signaling. Finally, in vivo experiments demonstrated that GClnc1 knockdown suppressed the growth and metastasis of SKOV3 and OVC1 cells in vivo. CONCLUSIONS: GClnc1 promoted NOTCH1 transcription by recruiting FOXC2, thereby activating the NF-κB/Snail signaling and promoting EOC cell growth and metastasis.

Wogonoside inhibits tumor growth and metastasis in endometrial cancer via ER stress-Hippo signaling axis.

Wogonoside, a bioactive flavonoid component derived from Scutellaria baicalensis Georgi, has been reported to inhibit tumor growth in mice bearing various types of cancer cells such as breast cancer, lung cancer, and leukemia cells. However, whether wogonoside could inhibit tumor growth of endometrial cancer has not been elucidated. In this study, we explored the function of wogonoside on tumor growth and the underlying mechanism on endometrial cancer. Firstly, we investigated the effect of wogonoside on endometrial cancer cells and found that wogonoside could significantly decrease cell proliferation and metastasis. Mechanistically, wogonoside could aggravate the extent of ER stress and upregulate the phosphorylation level of Mammalian Ste20-like kinase 1, leading to the activation of the Hippo signaling pathway. Taken together, in vitro and in vivo data demonstrated that wogonoside could be a potent inducer of ER stress and could be further developed into a promising therapy for endometrial cancer.

Upregulation of long non-coding RNA OGFRP1 facilitates endometrial cancer by regulating miR-124-3p/SIRT1 axis and by activating PI3K/AKT/GSK-3ß pathway.

We planned to investigate the possible influences of long non-coding RNA (opioid growth factor receptor pseudogene 1) OGFRP1 in endometrial cancer and its potential regulatory mechanism. We measured the level of OGFRP1 in endometrial cancer tissues and evaluated the influences of OGFRP1 dysregulation on the tumour cell biological processes of endometrial cancer cells. Further, the regulatory relationships between OGFRP1 and miR-124-3p, between miR-124-3p and Sirtuin1 (SIRT1) were, respectively, investigated. The interaction between OGFRP1 dysregulation and activation of PI3K/AKT/GSK-3ß pathway was revealed by Western blotting. OGFRP1 was up-regulated in endometrial cancer tissues and cells. OGFRP1 suppression inhibited the malignant behaviour (inhibited cell viability, promoted cell apoptosis, and suppressed cell migration and invasion) of the Ishikawa cells via negatively regulating miR-124-3p. SIRT1 was a target gene of miR-124-3p, and miR-124-3p regulated tumour growth and metastasis by the down-stream signal of SIRT1. Moreover, suppression of OGFRP1 restrained the activation of PI3K/AKT/GSK-3ß signals in the Ishikawa cells via miR-124-3p/SIRT1 axis. Our experiments revealed that upregulation of OGFRP1 may enhance the progression of endometrial cancer by regulating miR-124-3p/SIRT1 axis and by activating PI3K/AKT/GSK-3ß pathway. OGFRP1 may be of significance in illustrating the biology of endometrial cancer.

Clinicopathologic Features and Treatment Outcomes in Patients with Stage I, High-Risk Histology or High-Grade Endometrial Cancer after Primary Staging Surgery: A Taiwanese Gynecologic Oncology Group Study.

To investigate the clinicopathological features and treatment outcomes in patients with stage I, high-risk endometrial cancer. Patients with International Federation of Gynecology and Obstetrics stage I, papillary serous, clear cell, or grade 3 endometrioid carcinoma treated between 2000 and 2012 were analyzed for the clinical and pathological factors in relation to prognosis. A total of 267 patients (stage IA; n = 175, stage IB; n = 92) were included. Among the clinicopathological features, stage and age were significant prognostic factors. The recurrence rate and overall survival for stage IB versus IA were 22.8% versus 9.1% (p = 0.003) and 149.7 months versus 201.8 months (p < 0.001), respectively. The patients >60 years of age also had a higher recurrence rate (21.7% versus 9.7%, p = 0.008) and poorer survival (102.0 months versus 196.8 months, p = 0.001) than those ≤60 years of age. Distant recurrence (64.9%) occurred more frequently than local recurrence (24.3%) and local combined with distant recurrence (10.8%) (p < 0.001). The postoperative treatment modality had no impact on tumor recurrence rate, recurrence site, or overall survival. Distant recurrence is a major cause of treatment failure in patients with stage I, high-risk endometrial cancer. However, current adjuvant treatment appeared to have little effect in preventing its occurrence.

KLF16 suppresses human glioma cell proliferation and tumourigenicity by targeting TFAM.

BACKGROUND: This study aims to via unveiling the novel mechanisms of KLF16 in regulating expression of genes involved in glioma. METHODS: KLF16 or KLF16-siRNA was transfected to U87MG cells by lentivirus. Colony formation assay was applied for detecting cell proliferation. MTT assay was adopted to assess cell viability. TUNEL assay was selected to evaluate cell apoptosis. Flow cytometry was used to determine cell cycle. Real-time PCR was performed to test mRNA expression. Western blot was used to detect protein level. Luciferase assay was applied to confirm the regulatory relationship between KLF16 and Mitochondrial transcription factor A (TFAM). Chromatin immunoprecipitation was adopted to test the protein binding site. The nude mouse transplantation tumour experiment was selected to test cancer cell proliferation in vivo. RESULTS: KLF16 was decreased in glioma cells and tissues. KLF16 obviously restrained U87MG cell proliferation both in vivo and in vitro. KLF16 transfection reduced mRNA and protein levels related to cell proliferation. KLF16 targeted a putative binding site near the transcription start sites (TSSs) of TFAM gene, thus suppressing glioma cell proliferation. KLF16-siRNA exhibited the opposite impact. KLF16 presented significant negative correlation with TFAM level in glioma patients. CONCLUSIONS: KLF16 is a key regulator of glioma cell proliferation by directly targeting TFAM.

Outcomes of Patients With Surgically and Pathologically Staged IIIA-IVB Pure Endometrioid-type Endometrial Cancer: A Taiwanese Gynecology Oncology Group (TGOG-2005) Retrospective Cohort Study (A STROBE-Compliant Article).

In the management of patients with advanced-stage pure endometrioid-type endometrial cancer (E-EC), such as positive lymph nodes (stage III) or stage IV, treatment options are severely limited. This article aims to investigate the outcome of women with FIGO III-IV E-EC (based on FIGO 2009 system). The retrospective cohort study, based on the Taiwanese Gynecologic Oncology Group (TGOG-2005), enrolled patients undergoing staging surgery to have a pathologically confirmed FIGO III-IV E-EC from 22-member hospitals between 1991 and 2010. This cohort included 541 patients (stage III, n = 464; stage IV, n = 77). Five-year overall survival (OS) was 70.4%. Median progression-free survival (PFS) was 43 months (range 0-258 months) and median OS was 52 months (range 1-258 months). Multivariate analysis showed that FIGO stage, >1/2 myometrial invasion (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.12-2.09; P = 0.007), histological grade 3 (HR 2.0, 95% CI 1.47-2.75; P < 0.001), and metastases of pelvic and para-aortic lymph nodes (PLN and PALN) (HR 2.75, 95% CI 1.13-6.72; P < 0.001) were independent risk factors for PFS. FIGO stage, >1/2 myometrial invasion (HR 1.89, 95% CI 1.34-2.64; P < 0.001), and histological grade 3 (HR 2.42, 95% CI 1.75-3.35; P < 0.001) influenced OS. Complete dissection of PLN and PALN (HR 0.27, 95% CI 0.16-0.45; P < 0.001, and HR 0.14, 95% CI 0.08-0.26; P < 0.001) and the following paclitaxel-based therapy (HR 0.61, 95% CI 0.79-0.92; P = 0.017, and HR 0.48; 95% CI 0.31-0.75; P = 0.001) provided the better PFS and OS, respectively. In management of women with FIGO III-V E-EC, combination of complete staging surgery (complete dissection of PLN and PALN is included) and the following paclitaxel-based therapy could provide the better chance to survive. Patients with tumor >1/2 myometrial invasion and histological grade 3 are risky for disease-related mortality.

Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Papanicolaou smears.

OBJECTIVE: To study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears. MATERIALS AND METHODS: The medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests. RESULTS: The incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14-3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38-0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25-0.44, p<0.0001, respectively). CONCLUSIONS: Pregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components.

Outcome of ovarian preservation during surgical treatment for endometrial cancer: A Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: The goal of this study was to investigate the impact of ovarian preservation on the survival of women with early-stage endometrial cancer, particularly young women. MATERIALS AND METHODS: A study cohort of 64 patients with histologically confirmed early-stage endometrial cancer was retrospectively collected from 10 member hospitals of the Taiwanese Gynecologic Oncology Group between 1998 and 2009. Survivorship and overall survival were compared between these two groups using a log-rank test. RESULTS: All patients who underwent surgery were adult women with a mean age of 40.4 ± 9.2 years (range 24-63 years). Ovary-preserving surgery was performed in 38 (59.4%) patients who desired to preserve their ovaries, incidentally in 19 (29.7%) patients with a preoperative diagnosis other than endometrial carcinoma, and in seven patients (10.9%) with unknown reasons. The 5-year recurrence-free survival rate was 98.3% with a median follow up of 44.6 months (range 1.0-126.9 months). Eight patients required adjuvant treatment (12.5%); one patient had documented local recurrence (1.6%); and no metachronous ovarian malignancy occurred during follow up. CONCLUSION: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.

Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells.

BACKGROUND: Tanshinone IIA (TIIA), a diterpene quinone from the medicinal plant Salvia miltiorrhiza Bunge (Lamiaceae) was shown to possess apoptotic and TRAIL-sensitizing effects. Still, the molecular mechanisms whereby TIIA induces apoptosis remain largely unknown. PURPOSE: The role of survivin, an inhibitor of apoptosis protein, in TIIA-induced apoptosis has never been addressed before and hence was the primary goal of this study. METHODS: In this study, we explored the anticancer effect of TIIA in TOV-21G, SKOV3, and OVCAR3 ovarian carcinoma cells. Cytotoxicity was determined by MTS assay. Real-time RT-PCR and Western blotting were used to assess the mRNA and protein expression of related signaling proteins. RESULTS: Our results illustrated that TIIA's cytotoxic effect was caused by apoptosis with the involvement of caspases activity. Moreover, TIIA downregulated survivin in a concentration-dependent manner without affecting the expression of Bcl-2, Bcl-xL, and Bax. TIIA-induced survivin downregulation is regulated by both transcriptional processes and proteasomal degradation. Using TOV-21G cells as our cellular model, we demonstrated that TIIA-induced survivin downregulation requires p38 MAPK activation. Importantly, genetic overexpression of survivin rendered cells more resistant to TIIA, indicating an essential role of survivin downregulation in TIIA-induced apoptosis. This TRAIL sensitization effect of TIIA is ascribed to survivin downregulation because the effect was abrogated in cells that overexpressed survivin. CONCLUSION: Our findings provide new insights into the action modes of TIIA-mediated anticancer effects and further implicate a rational design for cancer therapeutic regimens by combining TIIA-sensitized TRAIL via downregulating survivin to elicit ovarian cancer cell death.