Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.

Decoding exercise-induced atomic components and prognostic shifts in endometrial carcinoma through differentially expressed genes

Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.

Effect of Estrogen and Antiestrogen on Chemotherapeutic Sensitivity of Endometrial Carcinoma Cell Line

Objective: To study the effect of estrogen and tamoxifen on chemotherapeutic sensitivity in ER(+) endometrial carcinoma cells.Methods: DNA fragmentation as the criteria for apoptotic cell death was used to evaluate the value of estrogen, tamoxifen and adriamycin in ER(+) endometrial carcinoma cells. DNA fragmentation was measured with the cell death ELISA.Results: Adriamycin and tamoxifen could induce apoptosis in ER(+) endometrial carcinoma cell. The cell apoptosis level was decreased with the increasing of 17-β-estradiol concentration (P<0.001) and was inversely proportional to 17-β-estradiol concentration (IgM) (P<0.01). The cell apoptosis level was increased with the increasing of tamoxifen concentration (P<0.01) and was also directly proportional to tamoxifen concentration (IgM). Furthermore, the cell apoptosis level was increased significantly after treated with both tamoxifen and adriamycin.Conclusion: Estrogen may block apoptosis induced by adriamycin in ER(+) endometrial carcinoma cell. Tamoxifen can increase the sensitivity of endometrial carcinoma cell to adriamycin. Tamoxifen combined with chemotherapeutic drug may be of significant therapeutic benefit in ER(+) endometrial carcinoma. Key words endometrial carcinoma - estrogen - tamoxifen - adriamycin - cell apoptosis

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Expressions of estrogen receptor subtypes and c-met proto-oncogene in endometrial carcinoma and their correlation

Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.

Mechanisms of inhibition by aspirin of endometrial carcinoma cell proliferation, migration and invasion

Objective:To investigate the effects and mechanisms of aspirin on the proliferation,migration and invasion of endometrial carcinoma HEC-1 A cell lines.Methods:HEC-1 Acells were cultured to the exponential phase and treated with different concentrations of aspirin(0.625 mmol/L,1.25 mmol/L,2.5 mmol/L,5 mmol/L and 10 mmol/L)for 24 to 120 hours.Cell proliferation was assessed by methyl thiazolyl tetrazolium(MTT)assay.The migration and invasion of HEC-1 Acells were detected by transwell assay.The protein expressions of vascular endothelial growth factor(VEGF)and ascular endothelial growth factor receptor 2(VEGFR-2)in HEC-1 Acells were determined by western blotting.Results:MTT results showed that aspirin inhibited the growth and proliferation of endometrial cancer cells in concentration and time-dependent manner.Aspirin had a significant inhibitory effect on the migration and invasion of HEC-1 Acells(P<0.05).In addition,aspirin obviously suppressed concentration-dependently the expression levels of VEGF and VEGFR-2(P<0.05).Conclusion:Aspirin could inhibit the proliferation,migration and invasion of endometrial cancer cells.The anti-tumor mechanism of aspirin might be related to the inhibition of tumor angiogenesis via blocking the VEGF/VEGFR-2 signaling pathway.

Effect of artesunate on human endometrial carcinoma HEC-1B cells

Objective： To observe the effect of the artesunate （ART） on cellular proliferation in vitro, to search for the possible anti-tumor mechanism of ART on endometrial carcinoma at the molecular level and to provide the experimental and theoretical foundations for the clinical applications of ART. Methods： The cell proliferation was observed by microscope; MTT was used to examine the effects of ART on proliferation of HEC-1B cells, and flow cytometric analysis was used to detect cell cycle and apoptosis. The human endometrial carcinoma HEC-1B cells were conventionally cultured; ART was administered with a concentration of 40 μg/ml before the total RNA were extracted, mRNA expression of Survivin, Caspase-3, N-Cadherin, E-Cadherin, Fibronectinl and Cox-2 were detected using RT-PCR. Results： ART reduced proliferation in human endometrial carcinoma cell line HEC-1B in a dose- and time-dependent effect. The cells of G0/G1 stage were significantly increased （P〈0.05）, but the cells of G2/M stages were significantly decreased （P〈0.05）, so it has shown that the cell cycle was probably blocked in G0/G1 stage. After intervention with ART at 20 and 80 μg/ml for 48 h, cellular apoptosis rate respectively was （36.42±0.77）% and （11.77±0.58）%, and the difference was statistically significant compared with the control （[6.64±0.191%, P〈0.01）. The expression of Cox-2 mRNA in the ART group was lower than those of control group, yet the expression of Caspase-3 and E-Cadherin mRNA in the ART group was higher than those of control group. Conclusion： ART can inhibit HEC-1B cell growth and proliferation in a dose- and time-dependent manner. Furthermore, ART can induce apoptosis in a dose-dependent manner. ART is able to downregulate Cox-2 mRNA expression and to upregulate E-Cadherin and Caspase-3 mRNA expression. So we can conclude that ART could induce the endometrial carcinoma HEC-1B cell apoptosis and inhibit tumor cell proliferation.

Effect of Celecoxib on Apoptosis of Endometrial Carcinoma Cell

Objective： To investigate the effect of Celecoxib on proliferation and apoptosis of the endometrial carcinoma cell HEC-1B and the effect on the expression of Fas and Survivin mRNA. Methods： The inhibition on the growth of human endometrial carcinoma cell HEC-1B was investigated by cell culture and MTT experiment when treated with different concentrations of Celecoxib. The cell apoptosis was detected by flow cytometry and DNA Ladder Electrophoresis. The change of the expression of Fas and Survivin mRNA after the treatment of Celecoxib was detected With RT-PCR. Results： Celecoxib could effectively inhibit the growth of HEC-1B cells and induce apoptosis. Survivin mRNA expression was decreased and Fas mRNA expression was increased after treating with Celecoxib. Conclusion： Celecoxib could inhibit HEC-1B cell proliferation and induce its apoptosis.

Adenovirus-mediated PTEN gene transfection suppresses growth and promotes chemosensitivity of endometrial carcinoma

Objective： To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma. Methods and Results： We constructed recombinant adenovirus carrying the wild-type PTEN gene （Ad-PTEN）. RL95-2 cells, an endometrial carcinoma cell line lacking PTEN function, was infected with Ad-PTEN and showed increased expression of PTEN and chemosensitivity to doxorubicin, decreased proliferation rate, and elevated apoptosis and Go/G1 arrest. Furthermore, the tumorigenicity of these cells was also completely suppressed. These results indicated that gene therapy with Ad-PTEN could significantly inhibit the endometrial carcinoma xenografts growth in nude mice by intratumoral injection, induce apoptosis of tumor cells, and reduce expression of proliferating cell nuclear antigen （PCNA）. Immunohistochemistry analysis also showed that the expression of progesterone receptors （PR） in Ad-PTEN treated tumor cells were induced, while P-glycoproteins （P-gp） and estrogen receptors （ER） decreased significantly. Conclusion： PTEN may play an important role in the development of endometrial carcinoma. Our findings cast new lights for treatment ofendometrial carcinoma.

Patterns of Recurrence and Their Significance in Patients with Endometrial Carcinoma<br>—For Improved Follow-Up after Initial Treatment<br>

Objectives: The aim of this study was to identify the patterns of recurrence and their significance in patients with endometrial carcinoma (EMCA). Patients and Methods: After a search of the medical records from single institutions, a total of 49 patients with relapsed endometrial carcinoma were retrospectively evaluated. Various clinical information was examined, including the site of recurrence, detection procedure, and presence or absence of any symptom at the time of recurrence. Furthermore, the postrecurrence survival analysis was based on the Kaplan-Meier method. Results: The median follow-up period of all patients was 39.4 months (5.8 - 293.1). In all, twenty-five (51.0%) patients experienced recurrence within 12 months after the final treatment. At the time of recurrence, 15 (30.6%) and 34 (69.4%) patients were symptomatic and asymptomatic, respectively. Among the 34 asymptomatic patients, recurrence was detected by CT scan in 14 (28.6%), tumor markers alone in 14 (28.6%), and pelvic examination/ultrasound scan in 5 (10.2%). There was no relapsed case detected by vaginal vault cytology alone. The 5-year postrecurrence survival rates in symptomatic and asymptomatic patients were 57.5 and 36.6 months, respectively (P = 0.2973). After recurrence, 12 patients underwent debulking surgery, and 37 received salvage chemotherapy or radiotherapy. The postrecurrence survival of patients receiving surgery did not differ from that of those with chemotherapy/radiotherapy (P = 0.9198). Conclusion: Although imaging studies and tumor marker measurement contributed to the early detection of recurrence, they did not necessarily improve the prognosis postrecurrence.

Correlation between the hemodynamic parameters of endometrial carcinoma and the expression of malignant biological molecules in the lesion

Objective: To study the correlation between the hemodynamic parameters of endometrial carcinoma and the expression of malignant biological molecules in the lesion. Methods:Patients with endometrial carcinoma who received surgical resection in Gaozhou Hospital of Traditional Chinese Medicine between March 2015 and December 2016 were selected as the malignant group of the research, healthy women who received physical examination during the same period were selected as the control group of the research, transvaginal color Doppler ultrasound was conducted to determine the resistance index (RI), and the endometrial cancer lesion and adjacent lesion were collected to detect the expression of proliferation and invasion molecules. Results: Endometrial RI of malignant group was significantly lower than that of control group;C-erB-2, COX-2, c-Myc, CD44V6, HPA, TET1 and RANKL mRNA expression levels in endometrial carcinoma lesions were significantly higher than those in adjacent lesions while DAPK3 and LKB1 mRNA expression levels were significantly lower than those in adjacent lesions;C-erB-2, COX-2, c-Myc, CD44V6, HPA, TET1 and RANKL mRNA expression levels in endometrial carcinoma lesions with high RI were significantly lower than those in endometrial carcinoma lesions with low RI while DAPK3 and LKB1 mRNA expression levels were significantly higher than those in endometrial carcinoma lesions with low RI. Conclusion: The hemodynamic parameters of endometrial carcinoma significantly reduce and are closely related to the proliferation and invasion of cells in the lesion.

Effects of TC regimen combined chemotherapy on serum levels of TSGF, PRL, HE4 and inflammatory factors in patients with endometrial carcinoma

Objective:To observe the effects of TC chemotherapy on the basis of surgical treatment on Endometrial carcinoma patients' serum TSGF, PRL, HE4 and TNF-α, CRP, VEGF, IL-8 levels.Methods:106 cases of endometrial carcinoma in our hospital from September 2014 to September 2016 were retrospectively analyzed and divided into control group and observation group, with 49 patients in the control group,57 patients in the observation group. All patients were given laparoscopic surgery, the patients in the observation group were given on the basis of laparoscopic surgery TC regimen (paclitaxel + carboplatin) chemotherapy for 2 courses, fasting venous blood before and after treatment in the morning was taken and centrifuged, and then used ELISA method to detect and compare the serum levels of TSGF, PRL, HE4 and TNF-α, CRP, VEGF, IL-8.Results: (1) Before treatment, there was no statistically significant difference in the serum TSGF, PRL, HE4 levels between the two groups. After treatment, compared with the same group before treatment, the serum TSGF, PRL, HE4 levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups;(2) Before treatment, there was no statistically significant difference in the serum TNF-α, CRP, VEGF, IL-8 levels between the two groups. After treatment, compared with the same group before treatment, the serum TNF-α, CRP, VEGF, IL-8 levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups.Conclusion:The treatment of TC chemotherapy on the basis of surgical treatment can significantly improve the patient's serum TSGF, PRL, HE4 and TNF-α, CRP, VEGF, IL-8 levels, it indicated that adjuvant chemotherapy with TC could not only improve the curative effect, control local recurrence of tumor, but also regulate the expression of some factors to inhibit the development of tumor, can also improve the internal inflammatory microenvironment, promote the patient's own immune expression, so it is worthy of clinical research and application.

Effects of concurrent chemoradiotherapy on serum tumor markers, MMP-9, VEGF and inflammatory factors in patients with endometrial carcinoma after operation

Objective:To investigate effects of concurrent chemoradiotherapy on serum tumor markers, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and inflammatory factors in patients with endometrial carcinoma after operation.Methods: A total of 86 patients with endometrial carcinoma treated by surgery were selected as objects of study, according to random data table they were divided into control group (n=42) and observation group (n=44), patients of two groups were all underwent hysterectomy and bilateral adnexectomy treatment, on this basis, the control group was given radiotherapy treatment, observation group patients received concurrent chemotherapy treatment, the levels of serum tumor markers, VEGF, MMP-9 and inflammatory factor of the two groups before and after treatment were compared.Results: Before treatment, there was no significant difference in CA-125, HE4, VEGF, MMP-9, TNF-α, CRP and IL-6 levels between the observation group and the control group;After treatment, the levels of CA-125, HE4, VEGF, MMP-9, TNF-α, CRP and IL-6 in the two groups were significantly lower than those in the group before treatment, and the difference was statistically significant;After treatment, the levels of CA-125, HE4, VEGF, MMP-9, TNF-α, CRP and IL-6 in the observation group were significantly lower than those in the control group, the difference was statistically significant.Conclusion:The concurrent radiotherapy and chemotherapy can effectively reduce the levels of serum tumor markers, VEGF and MMP-9, and effectively decrease the inflammatory stress response in patients with endometrial carcinoma after operation, with critical clinical value.

Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

Antidiastole Value of Three-dimensional Ultrasonography and Power Doppler between Uterine Parenchyma Lumps and Endometrial Cancer:A Retrospective Study

Sometimes endometrial polyps,submucosal myomas,and endometrial cancer show similar findings under ultrasonography.The aim of this study was to assess the antidiastole value of blood flow parameters using three-dimensional(3D)power Doppler ultrasonography angiography(PDA)between endometrial cancer and uterine parenchyma lumps.The data of the blood flow indices in 3D-PDA including the vascularization index(VI),flow index(FI),and vascularization flow index(VFI)in 40 patients with endometrial cancer and 41 patients with uterine parenchyma lumps(endometrial polyps and submucosal myomas)were retrospectively analysed and compared utilizing Virtual Organ Computer-aided AnaLysis(VOCAL)software.The results showed that all the blood flow parameters(VI,FI,VFI)were significantly higher in women with endometrial cancer than in those with uterine parenchyma lumps(P<0.001).The area under the curve of ROC of VI,FI,and VFI was 0.98,0.84,and 0.97,respectively.Thus,the best predictor of endometrial carcinoma was VI with a sensitivity of 97.0% and a specificity of 91.0%.The optimal cutoff value of VI was 4.06%.Our data demonstrated that all of the blood flow signal parameters(including VI,FI,and VFI)in 3D power Doppler ultrasonography had significant antidiastole values between endometrial cancer and uterine parenchyma lumps to assist clinicians in properly diagnosing patients.

Correlation between TAMs and proliferation and invasion of type endometrial carcinoma

Objective: To explore the correlation between tumor-associated macrophages and the proliferation and invasion of type endometrial carcinoma. Methods: Immunohistochemistry was used to investigate the infiltration of macrophages in normal and different types of hyperplastic endometrial lesions. The proliferation and invasion ability of type endometrial carcinoma cell line RL95-2 influenced by mononuclear macrophage cell line THP-1(constructed M2 type macrophages) was detected by CCK8 and transwell technologies respectively. Transwell was used to evaluate the recruiting ability of RL95-2 on THP-1 cells. Otherwise, the western blot was also used to detect the expression of Cyclin D1 and MMP-2 in RL95-2 with the influence of THP-1. Results: Immunohistochemistry result showed a positive correlation between the number of infiltrating macrophages and the progression of endometrial hyperplasia.THP-1 recruited by RL95-2 could promote its proliferation and invasion and enhance the expression of the Cyclin D1 and MMP-2 protein in a time dependent manner(P<0.05). Conclusions: Increase of the number of infiltrating macrophages and its contribution to the tumor inflammatory microenvironment may result in the development of the type endometrial carcinoma.

An elevated preoperative serum calcium level is a significant predictor for positive peritoneal cytology in endometrial carcinoma

Objective:To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma(EC).Methods:A total of 510 patients who were diagnosed with EC and had surgery were initially enrolled in this study at Peking University People's Hospital between January 2012 and December 2016.Clinical characteristics and preoperative serum calcium,albumin,carbohydrate antigen(CA)125,CA19-9,carcinoembryonic antigen(CEA)were extracted from patient records and evaluated according to postoperative peritoneal cytology.Predictive factors were assessed with Cox univariate and multivariate analyses.Factors selected from multivariate analysis results were used to build a predictive model.Results:A total of 510 patients are identified in our database and 444 patients who fulfilled inclusion and exclusion criteria are included in this study.Univariate analysis revealed that ionized calcium concentration was closely related to positive peritoneal cytology,tumor grade and lymph-vascular space invasion(LVSI).Moreover,peritoneal cytology was significantly associated with hypertension,tubal ligation,serum CA125,CA19-9,CEA and ionized calcium level.Multivariate analysis revealed that albumin-adjusted calcium level,CA125 and tubal ligation were independent predictive factors of positive peritoneal cytology(P<0.05).A combination of ionized calcium level with the other two indexes yielded significantly great area under the curve(AUC=0.824).Conclusions:This study enhanced the value of preoperative ionized calcium level.We also identified several potential biomarkers to predict positive peritoneal cytology in EC patients before surgery.

Value of ^(18)F-FDG PET/CT and MRI in diagnosing primary endometrial small cell carcinoma

Primary small cell carcinoma（SCC） is a group of aggressive neoplasms that mainly arise from the lung and digestive tract. Endometrial small cell carcinoma（ESCC） is extremely rare. To our knowledge, less than 90 cases have been reported, and most of these reports were dedicated to describing the clinicopathologic or immunochemical features of ESCC. Herein, we present a new case of ESCC involving a 51-year-old woman and mainly focus on the magnetic resonance imaging（MRI） and positron emission tomography/computed tomography（PET/CT） findings. MRI showed that the uterus was significantly enlarged（11.6 cm × 11.1 cm × 14.4 cm）, and a giant irregular mass（7.5 cm × 8.4 cm × 8.5 cm） was observed in the uterine cavity. The lesion demonstrated an extremely low apparent diffusion coefficient（ADC） value [（0.553±0.088）×10^–3 mm^2/s] and a high FDG uptake value（22.7）. Multiple metastatic lymph nodes（LNs） were identified at different positions, with diameters ranging from 0.3 to 2.8 cm and a maximum standardized uptake value（SUV max） ranging from 6.9 to 19.3.

Clinial Implication of tThe Expression of Aurora B in Normal Endometrium and Endometrial Carcinoma

The expression of Aurora B in normal endometria and endometrial carcinomas and its relation with clinicopathologic parameters of endometrial carcinomas were investigated. Streptavidin-biotin peroxidase （SP） immunohistochemical technique was used to detect the expression of Aurora B in 10 cases of normal proliferative phase endometria, 10 cases of normal secretory phase endometria and 72 cases of endometrial carcinomas respectively. According to the 1988 International Federation of Gynecology and Obstetrics （FIGO） grade, there were 37 patients in grade 1, 23 in grade 2 and 12 in grade 3 respectively. According to the FIGO stage, there were 59 patients in stage Ⅰ-Ⅱ and 13 patients in stage Ⅲ-Ⅳ. Aurora B was expressed in both normal proliferative phase endometria, secretory phase endometria and endometrial carcinomas, but its positive labeling index （PLI） in proliferative phase endometria was significantly higher than that in secretory phase endometria （P〈0.01） and endometrial carcinomas （P〈0.01）. The PLI of Aurora B was lower in tumors with well differentiation （G1）, low surgical staging （Ⅰ-Ⅱ）, and ≤1/2 myometrial invasion than that in tumors with moderate and low differentiation （G2--G3）, higher surgical staging （Ⅲ-Ⅳ）, and 〉1/2 myometrial invasion （all P〈0.01）. Aurora B exerts its functions in the replication of normal endometrial glandular cells; Expression of Aurora B is significantly correlated with biologic behavior of endometrial carcinoma, indicating that Aurora B may be a promising prognostic factor in endometrial carcinoma.

Apigenin, a natural flavonoid, promotes autophagy and ferroptosis in human endometrial carcinoma Ishikawa cells in vitro and in vivo

Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.