Correlation analysis of cancer stem cell marker CD133 and human endogenous retrovirus (HERV)-K env in SKOV3 ovarian cancer cells.

BACKGROUND: Human endogenous retrovirus (HERV)-K is a type of retrovirus that is present in the human genome, and its expression is usually silenced in healthy tissues. The precise mechanism by which HERV-K env influences cancer stemness is not fully understood, but it has been suggested that HERV-K env may activate various signaling pathways that promote stemness traits in cancer cells. OBJECTIVE: To establish the connection between HERV-K env expression and cancer stemness in ovarian cancer cells, we carried out correlation analyses between HERV-K env and the cancer stem cell (CSC) marker known as the cluster of differentiation 133 (CD133) gene in SKOV3 ovarian cancer cells. METHOD: To perform correlation analysis between HERV-K env and CSCs, ovarian cancer cells were cultured in a medium designed for cancer stem cell induction. The expression of HERV-K env and CD133 genes was verified using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analyses. Additionally, the expression of stemness-related markers, such as OCT-4 and Nanog, was also confirmed using RT-qPCR. RESULTS: In the stem cell induction medium, the number of tumorsphere-type SKOV3 cells increased, and the expression of CD133 and HERV-K env genes was up-regulated. Additionally, other stemness-related markers like OCT-4 and Nanog also exhibited increased expression when cultured in the cancer stem cell induction medium. However, when HERV-K env knockout (KO) SKOV3 cells were cultured in the same cancer stem cell induction medium, there was a significant decrease in the number of tumorsphere-type cells compared to mock SKOV3 cells subjected to the same conditions. Furthermore, the expression of CD133, Nanog, and OCT-4 did not show a significant increase in HERV-K env KO SKOV3 cells compared to mock SKOV3 cells cultured in the same cancer stem cell induction medium. CONCLUSION: These findings indicate that the expression of HERV-K env increased in SKOV3 cells when cultured in cancer stem cell induction media, and cancer stem cell induction was inhibited by KO of HERV-K env in SKOV3 cells. These results suggest a strong association between HERV-K env and stemness in SKOV3 ovarian cancer cells.

Comparison of survival outcome of open, total laparoscopic, and laparoscopy-assisted radical vaginal hysterectomy for stage IB2 cervical cancer patients: A multicenter retrospective study.

The aim of this study was to compare survival outcomes of 3 different radical hysterectomy (RH) types, namely total abdominal radical hysterectomy (TARH), total laparoscopic radical hysterectomy (TLRH), and laparoscopy-assisted radical vaginal hysterectomy (LARVH), in patients with FIGO stage IB2 cervical cancer. We retrospectively identified a cohort of patients who underwent RH for cervical cancer between 2010 and 2017. Patients with stage IB2 cervical cancer were included and were classified into TARH, TLRH, and LARVH treatment groups. Survival outcomes were estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were fit to estimate the independent association of RH technique with outcome. 194 patients were included in this study: 79 patients in the TARH group, 55 in the TLRH group, and 60 in the LARVH group. No significant differences were found in clinicopathological characteristics between the 3 RH groups. On comparing survival outcomes with TARH, both TLRH and LARVH showed no significant difference in terms of 5-year overall survival (TARH vs TLRH, P = .121 and TARH vs LARVH, P = .436). Conversely, compared to the TARH group, 5-year progression-free survival (PFS) was significantly worse in the TLRH group (P = .034) but not in the LARVH group (P = .288). Multivariate analysis showed that TLRH surgical approach (hazard ratio, 3.232; 95% confidence interval, 1.238-8.438; P = .017) was an independent prognostic factor for PFS in patients with IB2 cervical cancer. Our study suggests that in patients with FIGO stage IB2 cervical cancer, among the minimally invasive RH approaches, TLRH and LARVH, only TLRH approach was associated with worse PFS when compared with the TARH approach.

Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.

Rationale: The gut and its accessory organ, the liver, are crucial determinants of metabolic homeostasis via the regulation of circulating lipids for cardiovascular health. In response to environmental insults, cells undergo diverse adaptation or pathophysiological processes via stress-responsive eukaryotic initiation factor 2 alpha (eIF2α) kinase signaling and subsequent cellular reprogramming. We noted that patients with inflammatory gut distress display enhanced levels of ribosomal stress-responsive eIF2α kinase, which is notably associated with lipid metabolic process genes. Based on an assumption that eukaryotic ribosomes are a promising stress-responsive module for molecular reprogramming, chemical ribosome-inactivating stressors (RIS) were assessed for their involvement in enterohepatic lipid regulation. Methods: Experimental assessment was based on prediction using the clinical transcriptome and single-cell RNA-sequencing analysis of inflammatory bowel diseases and obesity. The prediction was verified using RIS exposure models of mice, gut organoids, and intestinal cells. The lipidomic profiling was performed to address RIS-induced intracellular fat alterations. Biochemical processes of the mechanisms were evaluated using RT-PCR, western blot analysis, luciferase reporter assays, and confocal microscopy of genetically ablated or chemically inhibited mice, organoids, and cells. Results: Chemical RIS including deoxynivalenol promoted enterohepatic lipid sequestration while lowering blood LDL cholesterol in normal and diet-induced obese mice. Although ribosomal stress caused extensive alterations in cellular lipids and metabolic genes, the cholesterol import-associated pathway was notably modulated. In particular, ribosomal stress enhanced gut levels of the low-density lipoprotein receptor (LDLR) via both transcriptional and post-transcriptional regulation. Subsequently, LDLR facilitated enterohepatic cholesterol accumulation, leading to dyslipidemia in response to ribosomal stress. Moreover, genetic features of stress-responsive LDLR modulators were consistently proven in the inflammation- and obesity-associated gut model. Conclusion: The elucidated ribosome-linked gut lipid regulation provides predictive insights into stress-responsive metabolic rewiring in chronic human diseases as an environmental health prediction.

Pulmonary cryptococcosis masquerading as lung metastasis in gynecologic cancers: Two case reports.

RATIONALE: Pulmonary cryptococcal infections occur mainly in immunocompromised individuals, such as those with malignancies. Preoperative diagnosis of pulmonary cryptococcosis (PC) can be challenging for both clinicians and radiologists because of nonspecific clinical manifestations and variable radiologic features, as it is easily misdiagnosed as metastatic lung cancer. PATIENT CONCERNS: In case 1, a 76-year-old woman with a history of cervical cancer presented with lung nodules detected on chest computed tomography (CT) 13 months after completing concurrent chemoradiotherapy. In case 2, a 56-year-old woman with a history of ovarian cancer presented with pulmonary nodules on chest CT 19 months after completing chemotherapy. Both patients were clinically asymptomatic, and tumor markers were not elevated. DIAGNOSES: In case 1, chest CT revealed multiple enhanced nodules with lobulated margins in the left lower lobe, and positron emission tomography (PET)-CT showed uptake in the nodule with a standardized uptake value of 3.7. In case 2, chest CT revealed several nodules in the right upper lobe abutting the right major fissure, and PET-CT revealed fluorodeoxyglucose uptake in the nodules. Pathology revealed granulomatous inflammation with cryptococcal infection, and mucicarmine and periodic acid-Schiff staining confirmed cryptococcal infection in both cases. INTERVENTIONS: Presumptive diagnoses of lung metastases were made in both cases and thoracoscopic lobectomy was performed. Postoperatively, the patients received antifungal therapy with fluconazole. OUTCOMES: PC was differentially diagnosed and effectively managed. The patients remained disease-free for both PC and gynecological cancers during subsequent follow-ups. LESSONS: Recognition that PC can mimic lung metastasis is important for managing gynecological cancers. PC should be considered in the differential diagnosis when single or multiple nodules are detected on chest radiography without elevation of tumor markers in patients with gynecological cancer.

Preoperative Haematologic Markers for the Differentiation of Endometrial Cancer from Benign Endometrial Lesions in Postmenopausal Patients with Endometrial Masses.

Purpose: The diagnostic value of preoperative hematological changes in endometrial cancer (EC) remains unclear. This study aimed to assess the role of preoperative hematologic parameters in differentiating EC from benign endometrial lesions in postmenopausal women with endometrial masses. Methods: Preoperative laboratory variables were retrospectively reviewed in patients with malignant or benign endometrial lesions, and the significance of intergroup differences was assessed. Receiver operating characteristic curves were used to analyze the optimal cut-off values for each variable. Logistic regression analysis was used to identify the variables predicting the presence of endometrial malignancy. Results: Preoperative laboratory variables of 176 patients (84 EC and 92 benign lesions) with endometrial masses were analyzed. Significant differences were observed between malignant and benign lesions in terms of WBC count, ANC, MCV, MPV, PDW, CA125, NLR, PMR, LMR, and SII (P < 0.05). Multivariate analyses showed that a high WBC count, high ANC, low MCV, low MPV, low PDW, high CA125, high NLR, high PMR, high LMR, and high SII independently predicted the presence of endometrial malignancy. Conclusion: The combination markers, MPV+PDW+NLR, had good discriminatory power for the presence of malignancy (AUC 0.797). Our results suggest that hematologic markers could be useful for the differentiation of malignant and benign endometrial lesions.

Security Framework for Network-Based Manufacturing Systems with Personalized Customization: An Industry 4.0 Approach.

Smart manufacturing is pivotal in the context of Industry 4.0, as it integrates advanced technologies like the Internet of Things (IoT) and automation to streamline production processes and improve product quality, paving the way for a competitive industrial landscape. Machines have become network-based through the IoT, where integrated and collaborated manufacturing system responds in real time to meet demand fluctuations for personalized customization. Within the network-based manufacturing system (NBMS), mobile industrial robots (MiRs) are vital in increasing operational efficiency, adaptability, and productivity. However, with the advent of IoT-enabled manufacturing systems, security has become a serious challenge because of the communication of various devices acting as mobile nodes. This paper proposes the framework for a newly personalized customization factory, considering all the advanced technologies and tools used throughout the production process. To encounter the security concern, an IoT-enabled NBMS is selected as the system model to tackle a black hole attack (BHA) using the NTRUEncrypt cryptography and the ad hoc on-demand distance-vector (AODV) routing protocol. NTRUEncrypt performs encryption and decryption while sending and receiving messages. The proposed technique is simulated by network simulator NS-2.35, and its performance is evaluated for different network environments, such as a healthy network, a malicious network, and an NTRUEncrypt-secured network based on different evaluation metrics, including throughput, goodput, end-to-end delay, and packet delivery ratio. The results show that the proposed scheme performs safely in the presence of a malicious node. The implications of this study are beneficial for manufacturing industries looking to embrace IoT-enabled subtractive and additive manufacturing facilitated by mobile industrial robots. Implementation of the proposed scheme ensures operational efficiency, enables personalized customization, and protects confidential data and communication in the manufacturing ecosystem.

A Comprehensive Study on Cyber Attacks in Communication Networks in Water Purification and Distribution Plants: Challenges, Vulnerabilities, and Future Prospects.

In recent years, the Internet of Things (IoT) has had a big impact on both industry and academia. Its profound impact is particularly felt in the industrial sector, where the Industrial Internet of Things (IIoT), also known as Industry 4.0, is revolutionizing manufacturing and production through the fusion of cutting-edge technologies and network-embedded sensing devices. The IIoT revolutionizes several industries, including crucial ones such as oil and gas, water purification and distribution, energy, and chemicals, by integrating information technology (IT) with industrial control and automation systems. Water, a vital resource for life, is a symbol of the advancement of technology, yet knowledge of potential cyberattacks and their catastrophic effects on water treatment facilities is still insufficient. Even seemingly insignificant errors can have serious consequences, such as aberrant pH values or fluctuations in the concentration of hydrochloric acid (HCI) in water, which can result in fatalities or serious diseases. The water purification and distribution industry has been the target of numerous hostile cyber security attacks, some of which have been identified, revealed, and documented in this paper. Our goal is to understand the range of security threats that are present in this industry. Through the lens of IIoT, the survey provides a technical investigation that covers attack models, actual cases of cyber intrusions in the water sector, a range of security difficulties encountered, and preventative security solutions. We also explore upcoming perspectives, illuminating the predicted advancements and orientations in this dynamic subject. For industrial practitioners and aspiring scholars alike, our work is a useful, enlightening, and current resource. We want to promote a thorough grasp of the cybersecurity landscape in the water industry by combining key insights and igniting group efforts toward a safe and dependable digital future.

High-Speed Network DDoS Attack Detection: A Survey.

Having a large number of device connections provides attackers with multiple ways to attack a network. This situation can lead to distributed denial-of-service (DDoS) attacks, which can cause fiscal harm and corrupt data. Thus, irregularity detection in traffic data is crucial in detecting malicious behavior in a network, which is essential for network security and the integrity of modern Cyber-Physical Systems (CPS). Nevertheless, studies have shown that current techniques are ineffective at detecting DDoS attacks on networks, especially in the case of high-speed networks (HSN), as detecting attacks on the latter is very complex due to their fast packet processing. This review aims to study and compare different approaches to detecting DDoS attacks, using machine learning (ML) techniques such as k-means, K-Nearest Neighbors (KNN), and Naive Bayes (NB) used in intrusion detection systems (IDSs) and flow-based IDSs, and expresses data paths for packet filtering for HSN performance. This review highlights the high-speed network accuracy evaluation factors, provides a detailed DDoS attack taxonomy, and classifies detection techniques. Moreover, the existing literature is inspected through a qualitative analysis, with respect to the factors extracted from the presented taxonomy of irregular traffic pattern detection. Different research directions are suggested to support researchers in identifying and designing the optimal solution by highlighting the issues and challenges of DDoS attacks on high-speed networks.

Evaluation of endometrial thickness in breast cancer patients with tamoxifen treatment - Difference between 2-dimensional ultrasonography and elastosonography.

OBJECTIVE: This study aimed to confirm the clinical significance of elastographic endometrium measurement in comparison with conventional ultrasonography for tamoxifen users with breast cancer. MATERIALS AND METHODS: In this retrospective analysis, 98 women receiving tamoxifen as postoperative breast cancer treatment were included. Patient medical charts were reviewed, and related medical, obstetric, and gynecological information and histories relevant to breast cancer were evaluated. Patient clinical imaging data included endometrial thickness measurements using both conventional ultrasonography and elastography, and the differences between these two modalities in delta values were statistically analyzed along with possible influencing factors. RESULTS: Endometrial thickness measured using 2-dimensional ultrasonography had a mean value of 5.81 mm (standard deviation [SD] = 3.09), and elastosonography showed a mean value of 3.07 mm (SD = 1.62). A paired t-test was conducted and a significant difference between them was confirmed (P-value <0.001). Logistic regression analysis revealed that age and duration of tamoxifen treatment significantly influenced the degree of difference between endometrial thickness measurements. CONCLUSIONS: Elastosonography may be a more successful and useful tool for measuring actual endometrial thickness than generalized 2-dimensional ultrasonography. In clinical cases with limited use of elastosonography and consequent inability for thorough evaluation of endometrial thickness, practitioners should exercise caution in deciding whether or not to adopt invasive diagnostic procedures, such as endometrial curettage, especially for young patients of reproductive age or those with prolonged treatment of breast cancer with tamoxifen.

Clinical Significance of the Combination of Serum HE4 Levels, Hemoglobin-to-Red Cell Distribution Width Ratio, and CT Imaging for the Pretreatment Assessment of Adnexal Masses.

Background: This study aimed to determine the optimal combination of biomarkers that can predict epithelial ovarian cancer (EOC) and compare the combination with the risk of ovarian malignancy algorithm (ROMA) or Copenhagen index (CPH-I). Methods: Data from 66 patients with EOC and 599 patients with benign ovarian masses who underwent definitive tissue diagnosis of adnexal masses between January 2017 and March 2021 were analyzed. The Mann-Whitney U test or Kruskal-Wallis test was used for between-group comparisons of medians. Logistic regression was used to establish an EOC predictor model. Area under the curve (AUC) comparisons between models were performed using the Delong nonparametric approach. Results: The median age of the patients was 43 years. Twenty-nine (43.9%) patients had early-stage disease (stages I-II) and 37 (56.1%) patients had advanced-stage disease (stages III-IV). The median age, body mass index, white blood cell count, hemoglobin-to-red cell distribution width ratio (HRR), platelet count, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, serum albumin level, cancer antigen 125, human epididymal secretory protein 4 (HE4), ROMA, and CPH-I were significantly different between the stage I-IV EOC and benign ovarian mass groups. Multivariate logistic regression analysis revealed that HE4, HRR, and computed tomography (CT) imaging were significant predictors of both stages I-IV and I-II EOC. Using these covariates, an interim model (IM) (consisting of HE4 and HRR) and a full model (FM) (consisting of HE4, HRR, and CT imaging) were constructed. When predicting stage I-IV EOC, the AUC of IM was comparable to that of ROMA or CPH-I, whereas the AUC of FM outperformed ROMA or CPH-I. In predicting stage I-II EOC, the AUC of IM was comparable to that of CPH-I but higher than that of ROMA, and the AUC of FM outperformed ROMA or CPH-I. Conclusion: FM outperformed ROMA or CPH-I in predicting stage I-IV EOC and stage I-II EOC. Therefore, FM could be a promising model for improving preoperative prediction of EOC at an early stage. However, further prospective studies are required to validate these results.

The stromal tumor-infiltrating lymphocytes, cancer stemness, epithelial-mesenchymal transition, and B7-H4 expression in ovarian serous carcinoma.

BACKGROUND: B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target. METHODS: A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. RESULTS: B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs. CONCLUSIONS: The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs.

Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues.

OBJECTIVE: The therapeutic effect of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer (EOC) with somatic BRCA mutations is consistent with that observed in patients with germline BRCA mutations, indicating the importance of detecting both germline and somatic BRCA mutations concurrently. We compared the efficacy of multi-gene panel next generation sequencing (NGS) in EOC patients' formalin-fixed, paraffin-embedded (FFPE) tissue to that of conventional Sanger sequencing in blood samples. MATERIALS AND METHODS: This study included 48 patients with EOC, and both blood Sanger sequencing and FFPE tissue NGS were conducted in all of them. Clinical and pathological data were reviewed, including age at diagnosis, histology, and stage. Blood Sanger sequencing was performed using peripheral blood leukocytes. The target regions of 90 cancer-related genes were identified using FFPE tissue. RESULTS: The median age of patients was 56.1 years, with serous carcinoma (n = 40, 83.3%) and stage III (n = 37, 77.1%) being the most common histology and International Federation of Gynecology and Obstetrics (FIGO) stage, respectively. FFPE tissue NGS identified ten pathogenic variants, including all eight pathogenic variants identified by blood Sanger sequencing and two additional pathogenic variants. Furthermore, FFPE tissue NGS identified 19 variants of uncertain significance (VUS), including all ten VUS identified by blood Sanger sequencing and nine additional VUS. CONCLUSION: The FFPE tissue multi-gene panel NGS had 100% sensitivity for detecting BRCA germline mutations and could detect additional somatic mutations. Furthermore, performing FFPE tissue multi-gene panel NGS followed by blood Sanger sequencing sequentially may help differentiate germline from somatic BRCA mutations for genetic counseling.

Caveolin-1-ACE2 axis modulates xenobiotic metabolism-linked chemoresistance in ovarian clear cell carcinoma.

Among epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) remains markedly resistant to platinum-based chemotherapy, leading to poor clinical outcomes. In response to xenobiotic insults, caveolar platforms play crucial roles in modulating stress signaling responses in cancer cells. It has been hypothesized that caveolin-1 (Cav-1), a main component of the lipid raft, may regulate the response to platinum-based treatment in OCCC. The clinical transcriptomic evaluation demonstrated that high Cav-1 expression was positively associated with a favorable prognosis in patients with ovarian cancer. Cav-1 overexpression enhanced sensitivity to cisplatin (CDDP) treatment, whereas Cav-1 deficiency promoted chemoresistance in OCCC cells. Mechanistically, although Cav-1 counteracted angiotensin-converting enzyme 2 (ACE2) expression, ACE2 positively facilitated resistance to CDDP in OCCC cells. Furthermore, ACE2 restricted aryl hydrocarbon receptor expression and subsequent transcription of drug-metabolizing enzymes. Of note, ACE2 positively regulated the expression of the platinum-clearing enzyme CYP3A4. These findings suggest that the Cav-1-ACE2 axis modulates xenobiotic metabolism-linked chemoresistance in OCCC, predicting potential roles for the stress sentinel networks in oncogenic processes.

The Discrepancy between Preoperative Tumor Markers and Imaging Outcomes in Predicting Ovarian Malignancy.

Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. Therefore, we evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We enrolled 1047 patients with ovarian tumors. The predictive values and concordance rates between the preoperative risk of ovarian malignancy algorithm (ROMA) and imaging, including CT and MRI, were evaluated. Diagnoses of 561 CT (77.9%) and 322 MRI group (69.2%) participants were consistent with the ROMA. Among them, 96.4% of the CT (541/561) and 92.5% of the MRI (298/322) group predicted an accurate diagnosis. In contrast, 67.3% (101/150) of CT and 75.2% (100/133) of MRI cases accurately predicted the diagnosis in cases with discrepancies between ROMA and CT or MRI; a total of 32% (48/150) of the CT and 25.5% (34/133) of the MRI group showed an accurate ROMA diagnosis in cases with discrepancies between ROMA and imaging. In the event of a discrepancy between ROMA and imaging when ovarian tumor malignancy prediction, the question is which method should take precedence. This study demonstrates that MRI has the greatest diagnostic accuracy, followed by CT and ROMA. It is also important to understand underlying diseases and benign conditions and rare histopathologies of malignant tumors.

A fertility-sparing surgery in lymphoepithelioma-like carcinomas of the uterine cervix: A case report.

INTRODUCTION: A poorly differentiated lymphoepithelioma-like carcinoma (LELC) of the cervix is an extremely rare presentation. We herein present an unusual case of LELC of the cervix, which was treated with radical trachelectomy for fertility preservation. PATIENT CONCERNS: A 28-year-old female patient presented with a 1-month-history of post-coital vaginal bleeding, and a 2 cm tumor was found on gynecological sonography and magnetic resonance imaging. DIAGNOSIS: The final pathological examination established a conclusive diagnosis of LELC of the cervix. After surgery, the patient was finally diagnosed as The International Federation of Gynecology and Obstetrics (FIGO) stage IB1 with no vaginal wall or parametrium infiltration. INTERVENTIONS: Subsequently, a surgery was scheduled, and intraoperatively, we performed resection twice because of a frozen biopsy result that was resection margin-positive initially. As a result, further resection was performed, which was a 5mm thickness for each. Cisplatin adjuvant chemotherapy was administered 3 weeks after the operation to prevent recurrence. OUTCOMES: The patient has been followed for 1 year postoperatively, with an adjuvant treatment, with no evidence of tumor recurrence or metastasis. CONCLUSION: Based on this case, we highly recommend that operators should consider a deeper resection margin range than that visible on magnetic resonance imaging. More attention is needed to better understand the treatment method for LELC of the cervix. We also plan to closely monitor the patient's prognosis and fertility, and to conduct additional studies.

Antibiotic-disrupted ribosome biogenesis facilitates tumor chemokine superinduction.

Upon exposure to internal or external stressors, ribosomes stand sentinel via modulation of ribosome assembly and protein translation. Ribosome-dependent cellular dysfunctions have been associated with pathophysiological processes during inflammation and tumorigenesis. In the present study, ribosome biogenesis was assessed to determine its effects on tumor chemokines, potentially contributing to cancer cell malignant features. In particular, ribosome biogenesis inhibition by antibiotic actinomycin D (ActD) enhanced the expression of chemokines in intestinal cancer cells under endoplasmic reticulum stress that governs multiple pro-tumoral reprogramming. Mechanistically, ribosome biogenesis inhibition superinduced proinflammatory chemokines via transcriptional and post-transcriptional regulation. Moreover, ribosomal stress-responsive p53 and its target macrophage inhibitory cytokine 1 (MIC-1) mediated chemokine superinduction by activating TGF-ß-activated kinase 1 (TAK-1) and nuclear factor-kappa B (NF-κB) in intestinal cancer cells. Cancer cell-based regulation of chemokine induction via MIC-1 signaling was verified using clinical transcriptome datasets. Clinical tumor tissue-derived MIC-1 was a positive regulator of chemokines and genes involved in the ribosome biogenesis pathway, supporting the in vitro assessments. Moreover, MIC-1-correlated chemokine expressions predicted poor prognoses in patients with colorectal cancer. Ribosome-based chemokine regulation via MIC-1 signaling would provide novel insights into translational interventions against malignant inflammatory insults.

MicroRNA-dependent inhibition of WEE1 controls cancer stem-like characteristics and malignant behavior in ovarian cancer.

Cancer stem-like cells (CSCs) have been suggested to be responsible for chemoresistance and tumor recurrence owing to their self-renewal capacity and differentiation potential. Although WEE1 is a strong candidate target for anticancer therapies, its role in ovarian CSCs is yet to be elucidated. Here, we show that WEE1 plays a key role in regulating CSC properties and tumor resistance to carboplatin via a microRNA-dependent mechanism. We found that WEE1 expression is upregulated in ovarian cancer spheroids because of the decreased expression of miR-424 and miR-503, which directly target WEE1. The overexpression of miR-424/503 suppressed CSC activity by inhibiting WEE1 expression, but this effect was reversed on the restoration of WEE1 expression. Furthermore, we demonstrated that NANOG modulates the miR-424/503-WEE1 axis that regulates the properties of CSCs. We also demonstrated the pharmacological restoration of the NANOG-miR-424/503-WEE1 axis and attenuation of ovarian CSC characteristics in response to atorvastatin treatment. Lastly, miR-424/503-mediated WEE1 inhibition re-sensitized chemoresistant ovarian cancer cells to carboplatin. Additionally, combined treatment with atorvastatin and carboplatin synergistically reduced tumor growth, chemoresistance, and peritoneal seeding in the intraperitoneal mouse models of ovarian cancer. We identified a novel NANOG-miR-424/503-WEE1 pathway for regulating ovarian CSCs, which has potential therapeutic utility in ovarian cancer treatment.

Effect of human endogenous retrovirus-K env gene knockout on proliferation of ovarian cancer cells.

BACKGROUND: Among various human endogenous retroviruses (HERVs), the HERV-K (HML-2) group has been reported to be highly related to cancer. In pancreatic cancer cells, shRNA-mediated downregulation of HERV-K env RNA decreases cell proliferation and tumor growth through the RAS-ERK-RSK pathway; in colorectal cancer, CRISPR-Cas9 knockout (KO) of the HERV-K env gene affects tumorigenic characteristics through the nupr-1 gene. OBJECTIVE: The effect of HERV-K env KO has not been studied in ovarian cancer cell lines. In this study, we analyzed the tumorigenic characteristics of ovarian cancer cell lines, including cell proliferation, migration, and invasion, and the expression patterns of related proteins after CRISPR-Cas9 KO of the HERV-K env gene. METHODS: The HERV-K env gene KO was achieved using the CRISPR-Cas9 system in ovarian cancer cell lines SKOV3 and OVCAR3. Tumorigenic characteristics including cell proliferation, migration, and invasion were analyzed, and related protein expression was investigated by western blot analysis. RESULTS: The expression of the HERV-K env gene in KO cells was significantly reduced at RNA and protein levels, and tumorigenic characteristics including cell proliferation, migration, and invasion were significantly reduced. In HERV-K env KO SKOV3 cells, the expression of the RB protein was significantly up-regulated and the cyclin B1 protein level was significantly reduced. In contrast, in HERV-K env KO OVCAR3 cells, the level of phospho-RB protein was significantly reduced, but other protein levels were not changed. CONCLUSION: The results of this study showed that HERV-K env gene KO affects cell proliferation, invasion, and migration of ovarian cells through RB and Cyclin B1 proteins, but the specific regulation pattern can differ by cell line.

Spontaneous reduction of transvaginal small bowel evisceration after abdominal hysterectomy for cervical cancer: A case report.

RATIONALE: Transvaginal evisceration of the small bowel is an extremely rare condition after hysterectomy, which requires urgent surgical intervention to prevent serious bowel morbidity and mortality. PATIENT CONCERNS: A 65-year-old woman presented with sudden-onset severe abdominal pain and a mass protruding through the vagina. The past surgical history was significant, with an abdominal hysterectomy for cervical cancer performed 11 weeks prior to presentation. DIAGNOSIS: Pelvic examination revealed prolapsed small-bowel loops (18-20 cm in length). Pelvic computed tomography scan confirmed the presence of transvaginal evisceration of the small bowel. INTERVENTIONS: Bowel reduction and urgent laparotomy were the selected treatment approaches for a detailed inspection and thorough washing of the intrα-abdominal cavity. A Foley catheter was inserted in the emergency room, with the subject in the lithotomy position. The prolapsed bowel loops spontaneously reduced without manual reduction, and the vault defect was repaired transvaginally. OUTCOMES: The patient experienced no postoperative complications and remained disease-free for 9months postoperatively. LESSONS: Transvaginal evisceration of the small bowel should be considered a surgical emergency. A multidisciplinary approach to prompt case management involving clinicians in gynecology, general surgery, and emergency medicine is vital for preventing serious consequences. Hysterectomy is the most frequently performed gynecological surgical procedure, and evisceration occurs most often after hysterectomy. Therefore, patients should be informed about this rare but possible hysterectomy complication.

Plasma-activated medium inhibits cancer stem cell-like properties and exhibits a synergistic effect in combination with cisplatin in ovarian cancer.

Ovarian cancer stem-like cells (CSCs) have been implicated in tumor recurrence, metastasis, and drug resistance. Accumulating evidence has demonstrated the antitumor effect of plasma-activated medium (PAM) in various carcinomas, including ovarian cancer. Thus, PAM represents a novel onco-therapeutic strategy. However, its impact on ovarian CSCs is unclear. Here, we show that ovarian CSCs resistant to high-dose conventional chemotherapeutic agents used for ovarian cancer treatment exhibited dose-dependent sensitivity to PAM. In addition, PAM treatment reduced the expression of stem cell markers and sphere formation, along with the aldehyde dehydrogenase- or CD133-positive cell population. We further investigated the effect of PAM in combination with other chemotherapeutics on ovarian CSCs in vitro. PAM exhibited synergistic cytotoxicity with cisplatin (CDDP) but not with paclitaxel and doxorubicin. In a peritoneal metastasis xenograft model established via intraperitoneal spheroid injection, PAM intraperitoneal therapy significantly suppressed peritoneal carcinomatosis (tumor size and number), with a more significant decrease observed due to the combined effects of PAM and CDDP with no side effects. Taken together, our results indicate that PAM inhibits ovarian CSC traits and exhibits synergetic cytotoxicity with CDDP, demonstrating PAM as a promising intraparietal chemotherapy for enhancing antitumor efficacy and reducing side effects.