TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism.

Recently, radioresistance has become a major obstacle in the radiotherapy of cervical cancer. To demonstrate enhanced radiosensitization against radioresistant cervical cancer, radioresistant cervical cancer cell line was developed and the mechanism of radioresistance was explored. Due to the overexpression of (death receptor 5, DR5) in cervical cancer, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressed cervical cancer cell membrane-camouflaged Cu2-xSe nanomedicine (CCMT) was designed. Since the CCMT was encapsulated with TRAIL-modified cell membrane, it represented high target to cervical cancer cell and immune evasion. Furthermore, Cu2-xSe had the ability to scavenge glutathione (GSH) and produce ·OH with excess H2O2 in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the 1O2 produced by X-rays. In vitro and in vivo studies elaborated that CCMT exhibited excellent radiosensitization properties to reverse radiotolerance by scavenging GSH and promoting DNA damage, apoptosis, mitochondrial membrane potential damage and metabolic disruption. Collectively, this study suggested that the development of TRAIL-overexpressed cell membrane-camouflaged Cu2-xSe nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment.

FBXO28 promotes cell proliferation, migration and invasion via upregulation of the TGF-beta1/SMAD2/3 signaling pathway in ovarian cancer.

BACKGROUND: Ovarian cancer is one of the most common gynecological malignancies due to the lack of early symptoms, early diagnosis and limited screening. Therefore, it is necessary to understand the molecular mechanism underlying the occurrence and progression of ovarian cancer and to identify a basic biomarker for the early diagnosis and clinical treatment of ovarian cancer. METHODS: The association between FBXO28 and ovarian cancer prognosis was analyzed using Kaplan‒Meier survival analysis. The difference in FBXO28 mRNA expression between normal ovarian tissues and ovarian tumor tissues was obtained from The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) cohorts. The expression levels of the FBXO28 protein in ovarian cancer tissues and normal ovarian tissues were measured via immunohistochemical staining. Western blotting was used to determine the level of FBXO28 expression in ovarian cancer cells. The CCK-8, the colony formation, Transwell migration and invasion assays were performed to evaluate cell proliferation and motility. RESULTS: We found that a higher expression level of FBXO28 was associated with poor prognosis in ovarian cancer patients. Analysis of the TCGA and GTEx cohorts showed that the FBXO28 mRNA level was lower in normal ovarian tissue samples than in ovarian cancer tissue samples. Compared with that in normal ovarian tissues or cell lines, the expression of FBXO28 was greater in ovarian tumor tissues or tumor cells. The upregulation of FBXO28 promoted the viability, proliferation, migration and invasion of ovarian cancer cells. Finally, we demonstrated that FBXO28 activated the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer. CONCLUSIONS: In conclusion, FBXO28 enhanced oncogenic function via upregulation of the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer.

DOCK1 regulates the malignant biological behavior of endometrial cancer through c-Raf/ERK pathway.

BACKGROUND: The effect of DOCK1 gene on the biological behavior of endometrial carcinoma cells and its related pathway has not been reported. METHODS: The immunohistochemical method and western blot were utilized to analyze DOCK1 protein expression in endometrial tissues and cells, respectively. CCK-8, BrdU, transwell and flow cytometry were performed to analyze the effect of DOCK1 expression changes on the viability, proliferation, invasion, migration and apoptosis of endometrial cancer cells, respectively. The effects of DOCK1 gene on Bcl-2, MMP9, Ezrin, E-cadherin and c-RAF/ERK1/2 signaling pathway were evaluated by western blot. The xenograft models were constructed to analyze the effect of DOCK1 in vivo. RESULTS: DOCK1 expression was increased in endometrial cancer tissues and cells compared with those in normal adjacent tissues and cells. DOCK1 knockout could inhibit the malignant biological behavior of endometrial cancer cells, while DOCK1 overexpression played the opposite effect. The expression of E-cadherin was upregulated and those of MMP9, Ezrin, Bcl-2, p-c-RAF (S338) and p-ERK1/2 (T202/Y204) were downregulated after DOCK1 knockout, while DOCK1 overexpression played the opposite effect. Additionally, Raf inhibitor LY3009120 reversed the function of DOCK1 on malignant biological behavior. In vivo experiment results showed that the growth and weight of transplanted tumors in nude mice were inhibited after DOCK1 knockout. The changes of E-cadherin, MMP9, Ezrin and Bcl-2 expressions in the transplanted tumors were consistent with those in vitro. CONCLUSION: DOCK1 could enhance the malignant biological behavior of endometrial cancer cells, which might be through c-RAF/ERK1/2 signaling pathways in vitro and in vivo.

Insight into the role of multiple signaling pathways in regulating cancer stem cells of gynecologic cancers.

Mounting evidence has demonstrated that a myriad of developmental signaling pathways, such as the Wnt, Notch, Hedgehog and Hippo, are frequently deregulated and play a critical role in regulating cancer stem cell (CSC) activity in human cancers, including gynecologic malignancies. In this review article, we describe an overview of various signaling pathways in human cancers. We further discuss the developmental roles how these pathways regulate CSCs from experimental evidences in gynecologic cancers. Moreover, we mention several compounds targeting CSCs in gynecologic cancers to enhance the treatment outcomes. Therefore, these signaling pathways might be the potential targets for developing targeted therapy in gynecologic cancers.

Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer.

OBJECTIVE: Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism. METHODS: This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analysed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, human monocytic THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarization. RESULTS: The results of bioinformatic analysis, IHC, qPCR and western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted protumour M2 macrophage polarization by upregulating cluster of differentiation 163 (CD163), CD206 and interleukin-10. CONCLUSIONS: Our study revealed that CPNE1 mediated M2 macrophage polarization and provided a therapeutic target for ovarian cancer.

Integrated analysis identifies RAC3 as an immune-related prognostic biomarker associated with chemotherapy sensitivity in endometrial cancer.

Endometrial cancer (EC) is one of the most common gynaecological malignant tumours with a high incidence, leading to urgent demands for exploring novel carcinogenic mechanisms and developing rational therapeutic strategies. The rac family of small GTPase 3 (RAC3) functions as an oncogene in various human malignant tumours and plays an important role in tumour development. However, the critical roles of RAC3 in the progression of EC need further investigation. Based on TCGA, single-cell RNA-Seq, CCLE and clinical specimens, we revealed that the RAC3 was specifically distributed in EC tumour cells compared to normal tissues and functioned as an independent diagnostic marker with a high area under curve (AUC) score. Meanwhile, the RAC3 expression in EC tissues was also correlated with a poor prognosis. In detail, the high levels of RAC3 in EC tissues were reversely associated with CD8+ T cell infiltration and orchestrated an immunosuppressive microenvironment. Furthermore, RAC3 accelerated tumour cell proliferation and inhibited its apoptosis, without impacting cell cycle stages. Importantly, silencing RAC3 improved the sensitivity of EC cells to chemotherapeutic drugs. In this paper, we revealed that RAC3 was predominantly expressed in EC and significantly correlated with the progression of EC via inducing immunosuppression and regulating tumour cell viability, providing a novel diagnostic biomarker and a promising strategy for sensitizing chemotherapy to EC.

SH3 domain-binding kinase 1 promotes proliferation and inhibits apoptosis of cervical cancer via activating the Wnt/ß-catenin and Raf/ERK1/2 signaling pathways.

SH3 domain-binding kinase 1 (SBK1), is a member of the serine/threonine protein kinases family, and was confirmed to be upregulated in cervical cancer in our previous study. Nonetheless, the role of SBK1 in regulating cancer occurrence and development is unclear. In this study, the stable SBK1-knockdown and -overexpressed cell models were constructed by plasmid transfection technology. Cell viability and growth were assessed through CCK-8, colony formation, and BrdU methods. Cell cycle and apoptosis were analyzed by flow cytometry. The JC-1 staining assay was used to explore mitochondrial membrane potential. The scratch and Transwell assays were used to evaluate the cell metastatic ability. The nude mice models were utilized to explore the SBK1 expression affecting tumor growth in vivo. Our research indicated a high expression of SBK1 both in tissues and cells of cervical cancer. The proliferative, migratory, as well as invasive capacities of cervical cancer cells, were suppressed, and apoptosis was enhanced after SBK1 silence, whereas SBK1 upregulation led to opposite results. In addition, Wnt/ß-catenin and Raf/ERK1/2 pathways were activated by SBK1 upregulation. Furthermore, downregulation of c-Raf or ß-catenin, reversed the proliferation promotion and apoptosis inhibition effects in SBK1-overexpressed cells. The same results were observed with the use of the specific Raf inhibitor. SBK1 overexpression also contributed to tumor growth in vivo. Overall, SBK1 played a vital role in cervical tumorigenesis via activating the Wnt/ß-catenin and Raf/ERK1/2 pathways.

Sustained expression of HPV16 E7 oncoprotein promotes p-AKT(Ser473)/p-Src(Tyr527) signaling to drive precancerous lesions to invasive cervical cancer.

Human papillomavirus (HPV) E7 oncogene plays the most important role in cervical cancer. However, whether E7 oncoprotein is continuously expressed, associated with AKT(Ser473)/p-Src(Tyr527) signaling to trigger cervical carcinogenesis remains unclear. Here, we explored first if HPV16 E7 oncoprotein could be detected in clinical biopsies and is sustainedly expressed, and then investigated how this oncoprotein interacted with AKT(Ser473)/p-Src(Tyr527) signaling in cancer progression. We used ZHPV16E7384 affibody to detect E7 expression in HPV16-positive cervical cancer biopsies and animal tumors by immunohistochemistry (IHC). Results showed that ZHPV16E7384 affibody had intense and specific staining for E7 oncoprotein in the detected specimen. The E7 oncoprotein was continuously expressed to correspond with the development of precancerous lesions to invasive cervical cancer. IHC staining also revealed that AKT, p-AKT(Ser473), Src and p-Src(Tyr527) proteins were expressed in both patient biopsies and animal tumors, with the highest levels of p-AKT(Ser473)/p-Src(Tyr527) present in invasive cancer. Furthermore, siRNA experiments revealed that HPV16 E7 knockdown significantly impaired expression of p-AKT(Ser473)/p-Src(Tyr527) in both HPV16 E7-positive cancer cells and transformed cells. In addition, transient expression of HPV16 E7 protein promoted significantly expression of p-AKT(Ser473)/p-Src(Tyr527) in primary human keratinocytes. Finally, co-immunoprecipitation analysis proved that HPV 16 E7 protein interacted reciprocally with p-AKT(Ser473)/p-Src(Tyr527). In conclusion, we demonstrate that HPV16 E7 oncoprotein is continuously expressed to promote expression of p-AKT(Ser473)/p-Src(Tyr527) leading to drive the initiation and progression of cervical cancer. Our data provide a novel insight that HPV16 E7 activates p-AKT(Ser473)/p-Src(Tyr527) to establish a mechanistic link between the oncogene and the AKT/Src signaling to trigger cervical carcinogenesis.

The functions of lncRNAs in the HPV-negative cervical cancer compared with HPV-positive cervical cancer.

Cervical cancer is one of the most common female malignancies. Human papillomaviruses (HPV) are the main causative agents of virtually all cervical carcinomas. Nevertheless, emerging evidence has demonstrated that a small proportion of cervical cancer patients are HPV negative. Long noncoding RNAs (lncRNAs) have been identified to play a crucial role in cervical cancer development. Here, this review describes the incidence and development of HPV-negative cervical cancer. Moreover, HPV-negative cervical cancers are more likely diagnosed at non-squamous type, older ages, more advanced stage and metastases, and associated with poorer prognosis as compared to HPV-positive cervical cancer. Furthermore, the significant role and functions of lncRNAs underlying HPV-negative cervical cancer is clarified.

Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells.

In the last decade, there has been a rapid expansion in tumor targeted therapy using mesenchymal stem cells (MSCs) based on their unique tropism towards cancer cells. Despite similarities in morphology, immunophenotype, and differential potent in vitro, MSCs originated from different tissues do not necessarily have equivalent biological behaviors. It is important to screen the most chemotactic MSCs to cancer cells. In this study, different MSCs were isolated from various human tissues including adipose, umbilical cord, amniotic membrane, and chorion. The chemotaxis of human MSCs to cervical cancer cells was measured by CCK-8, ELISA and Transwell invasion assays. Western blotting was performed to explore the underlying mechanisms. MSCs derived from distinct sources can be differently recruited to cervical cancer cells, among which chorion-derived MSC (CD-MSC) possessed the strongest tropic capacity. CXCL12 was found to be highly secreted by cervical cancer cells, in parallel with the expression of CXCR4 in all MSCs. CD-MSC displayed the highest level of CXCR4. These results indicated that CXCL12/CXCR4 pathway contributed to the different chemotaxis to cervical cancer cells of each MSCs. This study proposed that CD-MSC with the highest CXCR4 expression is a promising therapeutic vehicle for targeted therapy in cervical cancer.

In vivo and in vitro study of the potential hazards of surgical smoke during cervical cancer treatment with an ultrasonic scalpel.

OBJECTIVE: To explore the composition and potential hazards of cervical cancer surgical smoke generated by ultrasonic scalpels. METHODS: Surgical smoke was collected during the cutting and coagulation of cervical cancer xenograft tumors using an ultrasonic scalpel. Surgical smoke-filtered cells were cultured and subcutaneously injected into nude mice. Cell morphology and viability were assessed by HE, Pap and trypan blue staining. HPV DNA in surgical smoke samples was identified by PCR. HPV transmission was determined by culturing HPV-negative C33A cells in HPV-positive surgical smoke-filtered medium. The cytotoxicity of surgical smoke to small airway epithelial cells (SAECs) and THP-1 cells was determined by CCK-8, MTS and LDH release assays. Volatile organic compounds (VOCs), which are present in cervical cancer surgical smoke samples obtained by laparoscopic hysterectomy, were analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: Cellular debris and epithelioid cells were found in surgical smoke, but no malignant cells were observed. HPV DNA was identified in all smoke samples, and HPV genotypes were matched to those in cervical cancer cells. Coculture with HPV-positive surgical smoke-filtered medium induced an 83% (15 of 18) HPV positivity rate in C33A cells. Subculture in normal medium decreased this rate to 50% (9 of 18). The proliferation of SAECs and THP-1 cells was inhibited by smoke-filtered medium in a time-dependent manner. The concentration of total VOCs, especially benzene, toluene and xylene, in surgical smoke exceeded the standard for good indoor air quality. CONCLUSION: Cervical cancer surgical smoke contains HPV and VOCs and exhibits cytotoxicity and infectivity in vitro. Surgical smoke is an occupational hazard to health care workers.

Emerging Role of Ubiquitination in the Regulation of PD-1/PD-L1 in Cancer Immunotherapy.

A growing amount of evidence suggests that ubiquitination and deubiquitination of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) play crucial roles in the regulation of PD-1 and PD-L1 protein stabilization and dynamics. PD-1/PD-L1 is a major coinhibitory checkpoint pathway that modulates immune escape in cancer patients, and its engagement and inhibition has significantly reshaped the landscape of tumor clearance. The abnormal ubiquitination and deubiquitination of PD-1/PD-L1 influence PD-1/PD-L1-mediated immunosuppression. In this review, we describe the ubiquitination- and deubiquitination-mediated modulation of PD-1/PD-L1 signaling through a variety of E3 ligases and deubiquitinating enzymes (DUBs). Moreover, we briefly expound on the anticancer potential of some agents that target related E3 ligases, which further modulate the ubiquitination of PD-1/PD-L1 in cancers. Therefore, this review reveals the development of a highly promising therapeutic approach for cancer immunotherapy by targeting PD-1/PD-L1 ubiquitination.

Engineering cancer cell membrane-camouflaged metal complex for efficient targeting therapy of breast cancer.

BACKGROUND: Cancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility. RESULTS: Therefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo. CONCLUSION: In brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects.

Quantification and influencing factors of perioperative hidden blood loss in patients undergoing laparoscopic ovarian cystectomy for benign ovarian tumours.

This retrospective, monocentric study quantified hidden blood loss (HBL) and investigated its influencing factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy. Data from 153 patients who underwent laparoscopic ovarian cystectomy were retrospectively reviewed. HBL was calculated using the formula derived from 'Nadler' and 'Cross'. Pearson correlation was carried out to measure the association between HBL and potential risk factors. The average HBL was 280.22 ± 168.42 mL, accounting for 84.13 ± 19.20% of total blood loss (TBL) (347.48 ± 179.05 mL), which was a change of almost fourteen-fold relative to median visible blood loss [20.00 mL (10.00 mL, 57.5 mL)]. Surgical time, number of excisional tumours and preoperative albumin values were risk factors for HBL. HBL represents a large proportion more than 80% of TBL in patients undergoing laparoscopic ovarian cystectomy. Collectively, HBL is helpful for estimating intraoperative blood loss and better guidance of haemostatic agents, which reduces postoperative complications and expedites postoperative recovery. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.IMPACT STATEMENTWhat is already known on this subject? There has been a growing number of surgical patients with perioperative anaemia, which appears to be inconsistent with measured levels of visible intraoperative blood loss and postoperative drainage. This substantial but easily underestimated blood loss is known as hidden blood loss. To date, no published articles have evaluated HBL and its related risk factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy.What the results of this study add? HBL accounts for a large amount of TBL in laparoscopy for benign ovarian tumours. Surgical time, number of excisional tumours and preoperative albumin values are risk factors for HBL.What the implications are of these findings for clinical practice and/or further research? The management of HBL is important for the administration of perioperative blooding loss. In this context, HBL can be applied to estimate intraoperative blood loss and be better guidance of haemostatic agents to reduce postoperative complications and hasten postoperative rehabilitation. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.

Role of the COP1 protein in cancer development and therapy.

COP1, an E3 ubiquitin ligase, has been demonstrated to play a vital role in the regulation of cell proliferation, apoptosis and DNA repair. Accumulated evidence has revealed that COP1 is involved in carcinogenesis via targeting its substrates, including p53, c-Jun, ETS, ß-catenin, STAT3, MTA1, p27, 14-3-3σ, and C/EBPα, for ubiquitination and degradation. COP1 can play tumor suppressive and oncogenic roles in human malignancies, urging us to summarize the functions of COP1 in tumorigenesis. In this review, we describe the structure of COP1 and its known substrates. Moreover, we dissect the function of COP1 by physiological (mouse models), pathological (human tumor specimens) and biochemical (ubiquitin substrates) Evidence. Furthermore, we discuss COP1 as a potential therapeutic target for cancer therapy.

The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy.

Cancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.

Isoflurane promotes proliferation of squamous cervical cancer cells through mTOR-histone deacetylase 6 pathway.

This study investigated the effect of isoflurane on the proliferation of squamous cervical cancer cells, with focus on histone deacetylase 6 that is closely related to carcinogenesis. Squamous cervical cancer cells SiHa and Caski were exposed to 1%, 2%, or 3% isoflurane for 2 h, respectively. Cell proliferation was measured with the cell counting kit (CCK-8) assay and determined by BrdU assay. Expression of histone deacetylase 6, phospho-AKT, phospho-mTOR, and proliferating cell nuclear antigen (PCNA) was assessed by Western blot. In order to block the histone deacetylase 6 (HDAC6) expression, siRNA transfection was performed. Isoflurane significantly promoted the proliferation of both SiHa and Caski cells, accompanied by upregulation of PCNA protein expression. Isoflurane increased the level of histone deacetylase 6 protein expression in both cells, and knockdown of histone deacetylase 6 attenuated the pro-proliferation effects of isoflurane. Additionally, activation of AKT/mTOR was found after isoflurane treatment, and mTOR inhibition abolished isoflurane-induced histone deacetylase 6 expression. However, inhibition of AKT phosphorylation had no effect on the expression of histone deacetylase 6 mediated by isoflurane. In conclusion, Isoflurane enhanced proliferation of cervical cancer cells through upregulation of histone deacetylase 6, which was associated with mTOR-dependent pathway, but not AKT-mediated pathway.

Clinicopathological Features and Survival of Adolescent and Young Adults with Cervical Cancer.

PURPOSE: To explore clinicopathological characteristics and their prognostic value among young patients with cervical cancer (who are aged ≤25 years old). METHODS: The Surveillance, Epidemiology, and End Results Program (SEER) database was used to extract data on cervical cancer patients. They were then stratified by age as young women (≤25 years old) and old women (26-35 years old) and analyzed for clinicopathology characteristics and treatment modalities. Prognosis was analyzed using Kaplan-Meier survival curve, as well as hazard ratios using Cox regression modeling. The nomogram was developed based on Cox hazards regression model. RESULTS: Compared to 26-35 years old women, patients aged ≤25 years tended to be white ethnicity, unmarried, had earlier stage of disease. There was also a better prognosis among younger cohort. Grade, FIGO stage, histologic subtypes, and surgical modalities influenced the survival outcomes of young patients. Among young cohorts, surgery prolonged the survival time of IA-IIA stage patients while surgical and non-surgical management presented no statistically prognostic difference among patients at IIB-IVB stage. Besides, the nomogram which constructed according to Cox hazards regression model which contained independent prognosis factors including FIGO stage, surgery type, and histologic type of tumor can robustly predict survival of young patients. CONCLUSION: Cervical cancer patients ≤25 years old were uncommon and lived longer than the older patients. Among these young patients at IA-IIA stage, surgical treatment could be more effective at preventing death than non-surgery. The nomogram could perfectly predict the prognosis of young adults and adolescents with cervical cancer.

Erratum: Construction of a Competitive Endogenous RNA Network in Uterine Corpus Endometrial Carcinoma.

There was an error in Figure 4. The correct Figure 4 is provided below. The picture error would not affect the conclusion of the paper. Reference: Dong Ouyang, Ruyi Li, Yaxian Li, Xueqiong Zhu. Construction of a Competitive Endogenous RNA Network in Uterine Corpus Endometrial Carcinoma. Med Sci Monit 2019; 25:7998-8010. DOI: 10.12659/MSM.915798.

Relationship between thyroid disorders and uterine fibroids among reproductive-age women.

Uterine fibroids and thyroid nodules, both of which are crucially affected by estrogen, are common diseases among reproductive-age women. However, little attention has been paid to the association between the two diseases. This retrospective case-control study aimed to assess the relationships among thyroid nodules, thyroid function and uterine fibroids in China. We reviewed the electronic records of 853 reproductive-age women who attended health check-ups at the Second Affiliated Hospital of Wenzhou Medical University from July 1st, 2017, to June 30th, 2018. All subjects received transvaginal pelvic ultrasound, thyroid ultrasound, thyroid function, and other laboratory tests. We found that the prevalence of thyroid nodules in subjects with uterine fibroids was remarkably higher than that in subjects without fibroids. The proportion of thyroid nodules ≥1 cm in subjects with uterine fibroids was significantly higher than that in subjects without fibroids. Women with thyroid nodules had a higher proportion of multiple uterine fibroids than women without thyroid nodules. Among the parameters of thyroid function, the only statistically significant parameter was total triiodothyronine, i.e., women with uterine fibroids had lower total triiodothyronine levels than unaffected controls; however, the total triiodothyronine levels were within the normal ranges. Moreover, no significant difference was noted in thyroid hormone status between subjects with and without uterine fibroids. Our findings suggest that thyroid nodules are positively correlated with uterine fibroids among reproductive-age women in China. Further studies are needed to confirm this association and fully understand the common pathogenetic mechanism underlying the association between uterine fibroids and thyroid nodules.