OBJECTIVES: Previous studies have demonstrated that the metals cadmium and arsenic exhibit estrogen-like effects and may influence the occurrence and development of gynecological tumors. This study aims to explore the association between urinary cadmium and arsenic levels and the prevalence of gynecologic cancers using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Data from female participants in NHANES 2003-2018 were analyzed. Using R software, datasets (DEMO, BMX, etc.) were merged, and complete cases were retained by intersecting row names, yielding a total of 2 999 participants. After applying strict exclusion criteria, 2 802 participants were included: 83 with gynecologic cancer (cancer group) and 2 719 without (control group). Demographic, reproductive health, and urinary cadmium and arsenic data were collected. Binary Logistic regression models were employed to assess associations between urinary cadmium and arsenic levels and gynecologic cancer risk. RESULTS: High urinary cadmium and arsenic levels were risk factors for gynecologic cancers, with odds ratios (ORs) of 1.623 (95% CI 1.217 to 2.166) and 1.003 (95% CI 1.001 to 1.005), respectively. After propensity score matching (PSM), the trend remained; cadmium was still a statistically significant risk factor with an OR of 2.182 (95% CI 1.343 to 3.545), while arsenic's association, though not statistically significant, still trended toward risk (OR=1.004, 95% CI 0.999 to 1.009). Subgroup analyses showed that both cadmium and arsenic were risk factors for ovarian cancer (OR=1.745, 95% CI 1.178 to 2.586 and OR=1.005, 95% CI 1.002 to 1.008, respectively); these associations persisted after PSM. Additionally, cadmium increased the risk of endometrial cancer (OR=1.617, 95% CI 1.109 to 2.356). CONCLUSIONS Exposure to cadmium and arsenic is associated with an increased risk of ovarian and endometrial cancers. These findings suggest that reducing environmental exposure to heavy metals such as cadmium and arsenic may help prevent certain gynecologic cancers.
Humans ; Female ; Cadmium/urine* ; Arsenic/urine* ; Genital Neoplasms, Female/urine* ; Middle Aged ; Nutrition Surveys ; Adult ; Risk Factors ; Environmental Exposure/adverse effects* ; Aged

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

OBJECTIVES: Lymph node metastasis affects the initial treatment strategy for cervical cancer and is hard to be diagnosed in clinical practice.This paper aims to explore the relationship between calcium-binding A9 (S100A9) and lymph node metastasis (LNM) in cervical cancer, and to determine the predictive value of S100A9 for LNM in cervical cancer. METHODS: We performed a retrospective cohort study and collected the pathological data, follow-up data, and paraffin tissue samples of 99 patients with cervical cancer who underwent modified extensive or extensive hysterectomy plus pelvic lymphadenectomy at the Department of Gynecology, Xiangya Hospital, Central South University from January 2013 to December 2018. Immunohistochemistry was used to detect the expression of S100A9 in cervical cancer tissues, and the correlation between S100A9 expression and LNM of cervical cancer, or clinicopathological characteristics were analyzed. The receiver operating characteristic (ROC) curve was used to establish a predictive model for LNM of cervical cancer, and Chi-square test of four-grid table was used to evaluate the diagnostic value of S100A9 for LNM in cervical cancer. RESULTS: The expression of S100A9 was significantly correlated with LNM. The S100A9 immunohistochemical semi-quantitative score of the LNM group was significantly higher than that in the non-lymph node metastasis group (<0.001). Moreover, the expression of S100A9 was significantly correlated with histological type, stromal invasion, lymphatic vessel invasion, or LNM (<0.05). The cut-off of the ROC curve for predicting LNM was 5, with the Youden index of 0.649 and the area under the ROC curve of 0.863. The disease-free survival and overall survival in the S100A9 positive group were significantly shorter than those in the negative group (<0.05). S100A9 alone had a sensitivity of 71.4%, a specificity of 91.5%, and an accuracy of 85.1% for diagnosing LNM. Imaging had a sensitivity of 32.1%, a specificity of 74.6%, and an accuracy of 60.9%. Combination of S100A9 with image examination in parallel test had a sensitivity of 85.7%, a specificity of 71.2%, and an accuracy of 75.9%, while combination of S100A9 and image examination in serial test had a sensitivity of 17.9%, a specificity of 98.3%, and an accuracy of 72.4%. CONCLUSIONS S100A9 may be associated with LNM in cervical cancer. S100A9 shows a promising perspective in predicting LNM in cervical cancer. Combination of S100A9 and image examination in serial test has a high specificity for LNM.
Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Retrospective Studies ; Uterine Cervical Neoplasms

To investigate the correlation between soluble resistance-related calcium-binding protein (Sorcin) and chemoresistance or overall survival in patients with ovarian cancer.
 Methods: We detected the expression of Sorcin in 27 cases of chemoresistant ovarian cancer tissue and 37 cases of sensitive ovarian cancer tissue by immunohistochemistry, and analyzed the relationship between the protein and clinicopathological features or chemoresistance of ovarian cancer. Log-rank test was used to analyze the single factor impact on overall survival, Kaplan-Meier analysis was used to describe survival curve, and Cox proportional hazard model was used for multivariate analysis.
 Results: The immunoreactive scores for Sorcin in chemoresistant ovarian cancer tissues were higher than those in the sensitive ovarian cancer tissues (P<0.001). The levels of Sorcin inovarian cancer tissue did not show statistical significance with different ages, tumor stages, classifications, tissue types, degrees of ascites, omentums, and tumor metastases (P>0.05). The correlation between Sorcin and overall survival in resistant and sensitive ovarian cancer groups was not statistically significant (P>0.05), while there was a negative correlation between the expression of Sorcin and the overall survival of total cases (r=-0.326, P<0.05). Log-rank test showed that the drug resistance factor had a distinct impact on overall survival (P<0.001), and the Sorcin expression had an impact on overall survival (P<0.05). However, correlation between overall survival and the ages, ascites, omentum carcinoma, pathological types, pathological grade or FIGO staging was not significant (P>0.05). Cox proportional hazard model showed that drug resistance had a significant effect on overall survival (P<0.001), with a relative risk at 8.635, and the survival curve of the ovarian cancer sensitive group was obviously superior to that of ovarian cancer drug resistance group.
 Conclusion: Sorcin may be associated with drug resistance in ovarian cancer. The expression of Sorcin is correlated with the overall survival. The lower the Sorcin expression, the longer the survival time. Chemoresistance may act as an important independent prognostic factor for the poor prognosis for ovarian cancer.
Biomarkers, Tumor ; Carcinoma, Ovarian Epithelial ; Drug Resistance, Neoplasm ; Female ; Humans ; Kaplan-Meier Estimate ; Neoplasm Staging ; Ovarian Neoplasms ; Prognosis

Objective:To study the relationship between alpha seine/threonine-protein kinase (p-Akt)-serine/ threonine-protein kinase (mTOR)-ribosomal protein S6 kinase (p70S6K) signaling pathway and clinicopathological features or chemoresistance of ovarian cancer.Methods:We checked the p-Akt,mTOR and p70S6K protein levels in 18 tissues with chemoresistance or 25 with chemosensitivity of ovarian cancer by immunohistochemistry technique,and analyzed the relationship between those proteins and clinicopathological features or chemoresistance of ovarian cancer.Results:The levels of p-Akt protein in ovarian serous carcinoma,mucinous carcinoma and endometrioid carcinoma were 77.14%,50.00% and 66.67%,respectively,with no significant difference (P>0.05).The levels of these proteins in well-middle differentiated carcinoma and low differentiated carcinoma were 73.33% and 75.00%,respectively,with no significant difference (P>0.05).The levels of these proteins in Ⅰ-Ⅱ stage carcinoma,and Ⅲ-Ⅳ stage carcinoma were 18.18% and 93.75%,respectively,with significant difference (P<0.05).The levels ofmTOR protein in ovarian serous carcinoma,mucinous carcinoma and endometrioid carcinoma were 77.14%,100.00% and 83.33%,respectively,with no significant difference (P>0.05).The levels of this protein in well-middle differentiated carcinoma and low differentiated carcinoma were 80.00% and 78.57%,respectively,with no significant difference (P>0.05).The levels of this protein in Ⅰ-Ⅱ stage carcinoma,and Ⅲ-Ⅳ stage carcinoma were 27.27% and 96.88%,respectively,with significant difference (P<0.05).The levels of p70S6K protein in ovarian serous carcinoma,mucinous carcinoma and endometrioid carcinoma were 80.00%,100.00% and 100.00%,respectively,with no significant difference (P>0.05).The levels of this protein in well-middle differentiated carcinoma and low differentiated carcinoma were 93.33% and 78.57%,respectively,with no significant difference (P>0.05).The levels of this protein in Ⅰ-Ⅱ stage carcinoma,and Ⅲ-Ⅳ stage carcinoma were 45.45% and 96.88%,respectively,with significant difference (P<0.05).The levels of p-Akt protein in tissue of chemoresistance and chemosensitivity of ovarian cancer were 88.89% and 64.00%,respectively,with significant difference (P<0.05).The levels of mTOR protein in tissue of chemoresistance and chemosensitivity of ovarian cancer were 94.44% and 68.00%,respectively,with significant difference (P<0.05).The levels of p70S6K protein in tissue of chemoresistance and chemosensitivity of ovarian cancer were 100.00% and 72.00%,respectively,with significant difference (P<0.05).Conclusion:The p-Akt-mTOR-p70S6K signaling pathway may take part in invasion and metastasis of ovarian cancer.The up-regulation of these proteins may be associated with the chemoresistance of ovarian cancer,and these proteins may have potential to be the prognostic markers for the chemoresistance of ovarian cancer.

OBJECTIVE: To investigate the correlation of Annexin A1 (ANXA1) expression with paclitaxel response and clinicopathological features of ovarian carcinoma. METHODS: The expression levels of ANXA1 in ovarian carcinoma SKOV3/Taxol-25 and SKOV3 cell lines were detected by Western blot and real time-PCR. The expression of ANXA1 protein in 42 specimens of ovarian carcinoma was examined by immunhistochemistry. The correlation of ANXA1 expression with paclitaxel response and clinicopathological features of ovarian carcinoma was analyzed. RESULTS: The expression level of ANXA1 was significantly lower in SKOV3/Taxol-25 cell line than that in SKOV3 cell line (P<0.05). The positive specimens of ANXA1 expression in paclitaxel-resistant tissues (14/20) were significantly lower than those in the sensitive ones (21/22, P<0.05), and there was also a significant difference between the mild and the strong positive specimens (P<0.01). The expression of ANXA1 protein showed no correlation with the type of mophology and histological grade of ovarian cancer (P>0.05), but it was correlated with the clinical stage(P<0.05). CONCLUSION ANXA1 expression is downregulated in paclitaxel-resistant ovarian carcinoma, which might be a valuable predictor for paclitaxel susceptibility of ovarian carcinoma.
Annexin A1 ; metabolism ; Blotting, Western ; Down-Regulation ; Drug Resistance, Neoplasm ; Female ; Humans ; Ovarian Neoplasms ; drug therapy ; metabolism ; Paclitaxel ; pharmacology

OBJECTIVE: To determine the effect of RNA interference with transferred pshRNA/PHB on the biological characteristics of paclitaxel-resistant ovarian cancer cell lines. METHODS: Western blot and real time-PCR were used to assay the expression of PHB protein and mRNA in SKOV3/Taxol-25 and SKOV3 cell lines. The SKOV3/Taxol-25 cell lines were transiently transfected by 3 target-specific small hairpin RNA (shRNA) interference fragments with fluorescent protein named the pshRNA427/PHB1, pshRNA248/PHB2, and pshRNA136/PHB3. The empty plasmid transfection via vehicle Lipofectamine2000 served as a negative control. The expression levels of PHB protein and mRNA were detected by Western blot and real time-PCR after the transfection for 48 h. The silence effect of PHB1 and PHB3 groups was obvious. PHB1, PHB3, and the negative control groups were used for the following experiments. MTT and flow cytometry assay were used to test the cell proliferation, IC50 of paclitaxel, and cell apoptosis in the 3 groups. RESULTS: The expression levels of PHB protein and mRNA (2(-ΔΔCt)) were significantly higher in SKOV3/Taxol-25 cell line than those in SKOV3 cell line (P<0.05). The expression levels of PHB protein and mRNA were significantly lower in the PHB1 and PHB3 groups than those in the negative control group (P<0.05). The cell proliferations in the PHB1 and PHB3 groups were obviously slower than those in the negative control group after transfection for 48 h and 72 h (P<0.05). The IC50 of paclitaxel in the PHB1 and PHB3 groups significantly decreased after transfection for 72 h compared with the negative control group(P<0.05). The cell apoptotic rate in the PHB1 and PHB3 groups significantly increased after transfection for 48 h compared with the negative control group (P<0.05). CONCLUSION The shRNA/PHB can effectively suppress the expression of PHB gene in paclitaxel-resistant ovarian cancer cell lines. The cell proliferation in paclitaxel-resistant cell lines with removed PHB gene is significantly reduced. The apoptotic rate and the paclitaxel sensitivity of resistant cell lines with removed PHB gene are significantly increased. PHB gene is related to paclitaxel-resistance and interfering PHB gene expression may reduce paclitaxel resistance in ovarian cancer.
Antineoplastic Agents, Phytogenic ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Female ; Humans ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Paclitaxel ; pharmacology ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Repressor Proteins ; genetics ; metabolism ; Transfection ; Tumor Cells, Cultured

OBJECTIVE: To investigate the prevalence, etiology, clinical presentation and pathological features, treatment and prognosis of cervical cancer in young women. METHODS: Clinical data of 132 young women with cervical cancer were reviewed. RESULTS: Positive rate of human papillomavirus 18 was high in young women with cervical cancer. The primary clinical presentation of young patients with cervical cancer was contact bleeding of vagina, and the signs were out-expanding of cervical mass. The percentage of adenocarcinoma increased. The main treatment for cervical cancer was surgery. The patients had radical hysterectomy plus ovarian transplantation, none of whom had ovarian metastases and menopause syndrome. Prognosis of most patients was good. CONCLUSION Contact bleeding is a significant symptom in young women with cervical cancer. Surgery is first considered in the treatment. Preoperative neoadjuvant chemotherapy can be used in patients with locally advanced and late stage cervical cancer. Ovarian transplantation during operation can retain the ovary function.
Adult ; Age Factors ; Female ; Human papillomavirus 18 ; isolation & purification ; Humans ; Papillomavirus Infections ; complications ; Prognosis ; Uterine Cervical Neoplasms ; diagnosis ; surgery ; therapy ; virology ; Young Adult

OBJECTIVE: To study the proteins related to paclitaxel-resistant of ovarian cancer cell line. METHODS: The total proteins of paclitaxel-resistant and paclitaxel-sensitive human ovarian cancer cell lines were separated by 2-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were analyzed using image analysis software. The differential proteins were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Western blot was used to determine the differential expression levels of the 2 proteins. RESULTS: Forty differentially expressed proteins were found by image analysis software, and 24 differential proteins were identified by mass spectrometry. These proteins included proliferation cell nuclear antigen (PCNA), nm23, prohibitin (PHB), annexin, alpha-enolase, heat shock protein (HSP), and so on. CONCLUSION Twenty-four proteins in human ovarian cancer cell lines of paclitaxel-resistant and paclitaxel-sensitive are found by proteomic techniques, which may be involved in the paclitaxel-resistance of human ovarian cancer cells.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; genetics ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; NM23 Nucleoside Diphosphate Kinases ; analysis ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Proliferating Cell Nuclear Antigen ; analysis ; Proteome ; analysis ; Proteomics ; methods ; Repressor Proteins ; analysis

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on cervical carcinoma and its association with clinical data. METHODS: A total of 97 patients with stage Ib2 approximately IIIa of cervical cancinoma were treated with neoadjuvant chemotherapy. The effect of chemotherapy, factors associated with outcome of chemotherapy, and histology were analyzed. RESULTS: Effective rate of chemotherapy was 86.6% which was associated with clinical stage and histology. Eight-four patients received radical hysterectomy. The histological grade of 17 patients was lowered, lymph nodes in 19 patients were positive, and 6 patients had parametrium invasion. One patient died within 1 year after the operation, and 5 patients recurred. CONCLUSION The effect of neoadjuvant chemotherapy for locally advanced cervical cancinoma is good. Surgery after chemotherapy can improve the prognosis and 5-year survival rate.
Adenocarcinoma ; drug therapy ; mortality ; surgery ; Adult ; Carcinoma, Squamous Cell ; drug therapy ; mortality ; surgery ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; methods ; Prognosis ; Survival Rate ; Uterine Cervical Neoplasms ; drug therapy ; mortality ; surgery