Cervical Cancer Metastasis Research Articles

MicroRNA-153 Restrains Cell Metastasis and Epithelial–Mesenchymal Transition in Cervical Carcinoma by Targeting SATB1 and Regulating Wnt/β-Catenin Pathway

As a malignant tumor, cervical cancer (CC) seriously affects women’s life and health. Various microRNAs (miRNAs) are involved in tumorigenesis of CC. Here, we mainly paid attention to the effect of miR-153 in CC. RT-qPCR or Western blot was employed to quantify miR-153 or SATB1 expression. Molecular mechanism of miR-153/SATB1 was detected by Transwell and dual-luciferase assays. MiR-153 was downregulated in CC. Furthermore, upregulation of miR-153 restrained cell metastasis. Upregulation of SATB1 was detected in CC, and negative connected with miR-153 in CC cells. Knockdown of SATB1 suppressed cell metastasis in CC. The inhibitory effect of miR-153 was abolished by upregulation of SATB1. Besides that, miR-153 blocked EMT and downregulated p-β-catenin expression in CC cells. MiR-153 restrains cell metastasis and EMT in CC by targeting SATB1 and regulating Wnt/β-catenin pathway.

Predictive value and potential association of PET/CT radiomics on lymph node metastasis of cervical cancer

Objective: Due to the information-rich nature of positron emission tomography/computed tomography (PET/CT) images, the authors hope to explore radiomics features that could distinguish metastatic lymph nodes (LNs) from hypermetabolic benign LNs, in addition to conventional indicators. Methods: PET/CT images of 106 patients with early-stage cervical cancer from 2019 to 2021 were retrospectively analyzed. The tumor lesions and LN regions of PET/CT images were outlined with SeeIt, and then radiomics features were extracted. The least absolute shrinkage and selection operator (LASSO) was used to select features. The final selected radiomics features of LNs were used as predictors to construct a machine learning model to predict LN metastasis. Results: The authors determined two morphological coefficient characteristics of cervical lesions (shape – major axis length and shape – mesh volume), one first order characteristics of LNs (first order – 10 percentile) and two gray-level co-occurrence matrix (GLCM) characteristics of LNs (GLCM – id and GLCM – inverse variance) were closely related to LN metastasis. Finally, a neural network was constructed based on the radiomic features of the LNs. The area under the curve of receiver operating characteristic (AUC-ROC) of the model was 0.983 in the training set and 0.860 in the test set. Conclusion: The authors constructed and demonstrated a neural network based on radiomics features of PET/CT to evaluate the risk of single LN metastasis in early-stage cervical cancer.

Resveratrol, a novel inhibitor of fatty acid binding protein 5, inhibits cervical cancer metastasis by suppressing fatty acid transport into nucleus and downstream pathways.

Because of cervical cancer (CC) metastasis, the prognosis of diagnosed patients is poor. However, the molecular mechanisms and therapeutic approach for metastatic CC remain elusive. In this study, we first evaluated the effect of resveratrol (RSV) on CC cell migration and metastasis. Via an activity-based protein profiling (ABPP) approach, a photoaffinity probe of RSV (RSV-P) was synthesized, and the protein targets of RSV in HeLa cells were identified. Based on target information and subsequent in vivo and in vitro validation experiments, we finally elucidated the mechanism of RSV corresponding to its antimetastatic activity. The results showed that RSV concentration-dependently suppressed CC cell migration and metastasis. A list of proteins was identified as the targets of RSV, through the ABPP approach with RSV-P, among which fatty acid binding protein 5 (FABP5) attracted our attention based on The Cancer Genome Atlas (TCGA) database analysis. Subsequent knockout and overexpression experiments confirmed that RSV directly interacted with FABP5 to inhibit fatty acid transport into the nucleus, thereby suppressing downstream matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) expression, thus inhibiting CC metastasis. Our study confirmed the key role of FABP5 in CC metastasis and provided important target information for the design of therapeutic lead compounds for metastatic CC.

Protective effect of tretinoin on cervical cancer growth and proliferation through downregulation of pFAK2 expression.

Cervical cancer, a life-threatening disease, is the seventh most commonly detected cancer among women throughout the world. The present study investigated the effect of tretinoin on cervical cancer growth and metastasis in vitro and in vivo in the mice model. Cell Counting Kit-8, clonogenic survival, and transwell chamber assays were used for determination cells proliferation, colony formation, and invasiveness. Western blotting assay was used for assessment of protein expression whereas AutoDock Vina and Discovery studio software for in silico studies. Tretinoin treatment significantly (p < .05) reduced the proliferation of HT-3 and Caski cells in concentration-based manner. Incubation with tretinoin caused a significant decrease in clonogenic survival of HT-3 and Caski cells compared with the control cultures. The invasive potential of HT-3 cells was decreased to 18%, whereas that of Caski cells to 21% on treatment with 8 μM concentration of tretinoin. In HT-3 cells, tretinoin treatment led to a prominent reduction in p-focal adhesion kinase (FAK), matrix metalloproteinases (MMP)-2, and MMP-9 expression in HT-3 cells. Treatment of the cervical cancer mice model with tretinoin led to a prominent decrease in tumor growth. The metastasis of tumor in model cervical cancer mice group was effectively inhibited in spleen, intestines, and peritoneal cavity. In silico studies showed that tretinoin interacts with alanine, proline, isoleucine, and glycine amino acid residues of FAK protein to block its activation. The 2-dimensional diagram of interaction of tretinoin with FAK protein revealed that tretinoin binds to alanine and glycine amino acids through conventional hydrogen bonding. In summary, tretinoin suppressed the proliferation, colony formation, and invasiveness of cervical cancer cells in vitro. It decreased the expression of activated focal adhesion kinase, MMP-2, and MMP-9 in HT-3 cells in dose-dependent manner. In silico studies showed that tretinoin interacts with alanine and glycine amino acids through conventional hydrogen bonding. In vivo data demonstrated that treatment of the cervical cancer mice model with tretinoin led to a prominent decrease in tumor growth. Therefore, tretinoin can be developed as an effective therapeutic agent for cervical cancer treatment.

DHCR7 promotes lymph node metastasis in cervical cancer through cholesterol reprogramming-mediated activation of the KANK4/PI3K/AKT axis and VEGF-C secretion

Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. However, the molecular mechanism of LNM in CC is unclear, and there is no effective clinical treatment. Here, we found that 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the last step of cholesterol synthesis, was upregulated in CC and closely related to LNM. Gain-of-function and loss-of-function experiments proved that DHCR7 promoted the invasion ability of CC cells and lymphangiogenesis in vitro and induced LNM in vivo. The LNM-promoting effect of DHCR7 was partly mediated by upregulating KN motif and ankyrin repeat domains 4 (KANK4) expression and subsequently activating the PI3K/AKT signaling pathway. Alternatively, DHCR7 promoted the secretion of vascular endothelial growth factor-C (VEGF-C), and thereby lymphangiogenesis. Interestingly, cholesterol reprogramming was needed for the DHCR7-mediated promotion of activation of the KANK4/PI3K/AKT axis, VEGF-C secretion, and subsequent LNM. Importantly, treatment with the DHCR7 inhibitors AY9944 and tamoxifen (TAM) significantly inhibited LNM of CC, suggesting the clinical application potential of DHCR7 inhibitors in CC. Collectively, our results uncover a novel molecular mechanism of LNM in CC and identify DHCR7 as a new potential therapeutic target.

Hematological indicator-based machine learning models for preoperative prediction of lymph node metastasis in cervical cancer.

Lymph node metastasis (LNM) is an important prognostic factor for cervical cancer (CC) and determines the treatment strategy. Hematological indicators have been reported as being useful biomarkers for the prognosis of a variety of cancers. This study aimed to evaluate the feasibility of machine learning models characterized by preoperative hematological indicators to predict the LNM status of CC patients before surgery. The clinical data of 236 patients with pathologically confirmed CC were retrospectively analyzed at the Gynecology Oncology Department of the First Affiliated Hospital of Bengbu Medical University from November 2020 to August 2022. The least absolute shrinkage and selection operator (LASSO) was used to select 21 features from 35 hematological indicators and for the construction of 6 machine learning predictive models, including Adaptive Boosting (AdaBoost), Gaussian Naive Bayes (GNB), and Logistic Regression (LR), as well as Random Forest (RF), Support Vector Machines (SVM), and Extreme Gradient Boosting (XGBoost). Evaluation metrics of predictive models included the area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1-score. RF has the best overall predictive performance for ten-fold cross-validation in the training set. The specific performance indicators of RF were AUC (0.910, 95% confidence interval [CI]: 0.820-1.000), accuracy (0.831, 95% CI: 0.702-0.960), specificity (0.835, 95% CI: 0.708-0.962), sensitivity (0.831, 95% CI: 0.702-0.960), and F1-score (0.829, 95% CI: 0.696-0.962). RF had the highest AUC in the testing set (AUC = 0.854). RF based on preoperative hematological indicators that are easily available in clinical practice showed superior performance in the preoperative prediction of CC LNM. However, investigations on larger external cohorts of patients are required for further validation of our findings.

The inhibition of YTHDF3/m6A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer.

The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (m6A), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions. This study demonstrated a clinical correlation between the upregulation of the m6A reader YTHDF3 and LN metastasis, thereby contributing to poor overall survival probability (OS) among CCa patients. The mechanistic investigation revealed that SREBF1 transcriptionally activated YTHDF3 expression by binding to its promoter. Functional experiments demonstrated that the upregulation of YTHDF3 significantly enhanced the in vitro proliferative, migratory, and invasive capacities of CCa cells, while also promoting lymphangiogenesis and facilitating LN metastasis in vivo. Mechanistically, the upregulation of LRP6 through YTHDF3-mediated m6A modification resulted in increased expression of FASN and ACC1, leading to both lipolysis of lipid droplets and synthesis of free fatty acid. Ultimately, this promoted fatty acid metabolism and enhanced LN metastasis by activating the LRP6-YAP-VEGF-C axis, which could induce lymphangiogenesis in CCa. Our study highlighted that YTHDF3 can serve as a promising therapeutic target and predictive biomarker for CCa patients with LN metastasis.

AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis.

Unrestrained chronic inflammation leads to the abnormal activity of NOX4 and the subsequent production of excessive hydrogen peroxide (H2O2). Excessive H2O2 signaling triggered by prolonged inflammation is thought to be one of the important reasons for the progression of some types of cancer including cervical cancer. Aquaporin 3 (AQP3) is a member of the water channel protein family, and it remains unknown whether AQP3 can regulate the transmembrane transport of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)-derived H2O2 induced by the stimulation of inflammatory factors to facilitate the malignant progression in cervical cancer. In this study, cervical cancer HeLa cell line was respectively treated with diphenyleneiodonium (DPI), N-Acetylcysteine (NAC) or lentivirus-shRNA- AQP3. Plate cloning, cell migration or transwell invasion assays, etc. were performed to detect the invasive and migration ability of the cells. Western blot and CO-IP were used to analyze the mechanism of AQP3 regulating H2O2 conduction. Finally, in vivo assays were performed for validation in nude mice. AQP3 Knockdown, DPI or NAC treatments all reduced intracellular H2O2 influx, and the activation of Syk/PI3K/Akt signal axis was inhibited, the migration and invasive ability of the cells was attenuated. In vivo assays confirmed that the excessive H2O2 transport through AQP3 enhanced the infiltration and metastasis of cervical cancer. These results suggest that AQP3 activates H2O2/Syk/PI3K/Akt signaling axis through regulating NOX4-derived H2O2 transport to contribute to the progression of cervical cancer, and AQP3 may be a potential target for the clinical treatment of advanced cervical cancer.

Epitranscriptomics and cervical cancer: the emerging role of m6A, m5C and m1A RNA modifications.

Cervical cancer (CC), one of the most prevalent and detrimental gynaecologic cancers, evolves through genetic and epigenetic alterations resulting in the promotion of oncogenic activity and dysfunction of tumour-suppressing mechanisms. Despite medical advancement, the prognosis for advanced-stage patients remains extremely low due to high recurrence rates and resistance to existing treatments. Thereby, the search for potential prognostic biomarkers is heightened to unravel new modalities of CC pathogenesis and to develop novel anti-cancer therapies. Epitranscriptomic modifications, reversible epigenetic RNA modifications, regulate various biological processes by deciding RNA fate to mediating RNA interactions. This narrative review provides insight into the cellular and molecular roles of endogenous RNA-editing proteins and their associated epitranscriptomic modifications, especially N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A), in governing the development, progression and metastasis of CC. We discussed the in-depth epitranscriptomic mechanisms underlying the regulation of over 50 RNAs responsible for tumorigenesis, proliferation, migration, invasion, survival, autophagy, stemness, epithelial-mesenchymal transition, metabolism (glucose, lipid, glutamate and glutamine), resistance (drug and radiation), angiogenesis and recurrence of CC. Additionally, we provided a concise overview of the therapeutic potential of targeting the altered expression of endogenous RNA-editing proteins and aberrant deposition of RNA modifications on both coding and non-coding RNAs in CC.

Preoperative magnetic resonance imaging-radiomics in cervical cancer: a systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to evaluate the potential significance of radiomics, derived from preoperative magnetic resonance imaging (MRI), in detecting deep stromal invasion (DOI), lymphatic vascular space invasion (LVSI) and lymph node metastasis (LNM) in cervical cancer (CC). A rigorous and systematic evaluation was conducted on radiomics studies pertaining to CC, published in the PubMed database prior to March 2024. The area under the curve (AUC), sensitivity, and specificity of each study were separately extracted to evaluate the performance of preoperative MRI radiomics in predicting DOI, LVSI, and LNM of CC. A total of 4, 7, and 12 studies were included in the meta-analysis of DOI, LVSI, and LNM, respectively. The overall AUC, sensitivity, and specificity of preoperative MRI models in predicting DOI, LVSI, and LNM were 0.90, 0.83 (95% confidence interval [CI], 0.75-0.89) and 0.83 (95% CI, 0.74-0.90); 0.85, 0.80 (95% CI, 0.73-0.86) and 0.75 (95% CI, 0.66-0.82); 0.86, 0.79 (95% CI, 0.74-0.83) and 0.80 (95% CI, 0.77-0.83), respectively. MRI radiomics has demonstrated considerable potential in predicting DOI, LVSI, and LNM in CC, positioning it as a valuable tool for preoperative precision evaluation in CC patients.

18F-FDG PET/CT semi-quantitative parameters combined with SCC-Ag in predicting lymph node metastasis in stage I-II cervical cancer.

To explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II). A total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM. There were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p<0.01). Logistic regression analysis showed that TLG was an independent predictor of LNM in stage I-II cervical cancer (OR 1.032, 95% CI 1.013-1.052, p<0.01). Moreover, the predictive value of TLG combined with SUVpeak and SCC-Ag increased and the area under the curve increased compared SUVpeak and SCC-Ag. 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag have promise for assessing LNM in stage I-II cervical cancer. TLG of primary tumor provides independent and increasing values in predicting LNM in stage I-II cervical cancer.

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis.

Background: Tyrosine kinase with immunoglobulin and EGF-like domains 1 (TIE1) is known as an orphan receptor prominently expressed in endothelial cells and participates in angiogenesis by regulating TIE2 activity. Our previous study demonstrated elevated TIE1 expression in cervical cancer cells. However, the role of TIE1 in cervical cancer progression, metastasis and treatment remains elusive. Methods: Immunohistochemistry staining for TIE1 and Basigin was performed in 135 human cervical cancer tissues. Overexpressing vectors and siRNAs were used to manipulate gene expression in tumor cells. Colony formation, wound healing, and transwell assays were used to assess cervical cancer cell proliferation and migration in vitro. Subcutaneous xenograft tumor and lung metastasis mouse models were established to examine tumor growth and metastasis. Co-Immunoprecipitation and Mass Spectrometry were applied to explore the proteins binding to TIE1. Immunoprecipitation and immunofluorescence staining were used to verify the interaction between TIE1 and Basigin. Cycloheximide chase assay and MG132 treatment were conducted to analyze protein stability. Results: High TIE1 expression was associated with poor survival in cervical cancer patients. TIE1 overexpression promoted the proliferation, migration and invasion of cervical cancer cells in vitro, as well as tumor growth and metastasis in vivo. In addition, Basigin, a transmembrane glycoprotein, was identified as a TIE1 binding protein, suggesting a pivotal role in matrix metalloproteinase regulation, angiogenesis, cell adhesion, and immune responses. Knockdown of Basigin or treatment with the Basigin inhibitor AC-73 reversed the tumor-promoting effect of TIE1 in vitro and in vivo. Furthermore, we found that TIE1 was able to interact with and stabilize the Basigin protein and stimulate the Basigin-matrix metalloproteinase axis. Conclusion: TIE1 expression in cervical cells exerts a tumor-promoting effect, which is at least in part dependent on its interaction with Basigin. These findings have revealed a TIE2-independent mechanism of TIE1, which may provide a new biomarker for cervical cancer progression, and a potential therapeutic target for the treatment of cervical cancer patients.

Elevated INHBA Promotes Tumor Progression of Cervical Cancer.

Objectives: This study aimed to explore the role of inhibin subunit beta A (INHBA) in the progression of cervical cancer (CCa) and investigate its potential as a therapeutic target. Specifically, the objectives were to assess the expression levels of INHBA in CCa, examine its correlation with patient survival, and elucidate its impact on CCa cell proliferation, cell cycle regulation, migration, invasion, and in vivo tumor growth and metastasis. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. INHBA expression in CCa was analyzed, and its association with patient survival was assessed using clinical data. In vitro experiments involved the investigation of INHBA's effects on CCa cell proliferation, cell cycle dynamics, migration, and invasion through the epithelial-mesenchymal transition (EMT) process. Additionally, in vivo experiments were performed to evaluate the influence of INHBA on CCa growth and lung metastasis. Results: The results of this study revealed upregulated expression of INHBA in CCa, with a significant association between high INHBA expression and poor patient survival. Functionally, INHBA was found to promote the proliferation of CCa cells, regulate the cell cycle, and enhance migration and invasion through the EMT process in vitro. Moreover, in vivo experiments demonstrated that INHBA facilitated the growth and lung metastasis of CCa. Conclusion: In conclusion, our findings suggest that INHBA plays a crucial role in the progression of cervical cancer. The upregulation of INHBA is associated with poor patient survival, and its involvement in promoting key aspects of cancer progression makes it a potential therapeutic target for CCa treatment. These results provide valuable insights into the molecular mechanisms underlying CCa and offer a foundation for further exploration of targeted therapeutic interventions.

The effects of PIK3CA mutations on cervical cancer

Cervical cancer is one of the major problems affecting women’s health worldwide. Dysregulation of cellular signalling pathways, PI3K-Akt axis, in particular, may be linked to the development and malignant metastasis of cervical cancer. PIK3CA gene codes a catalytic subgroup of phosphatidylinositol 3-Kinase A (PI3K-A), which is an essential element in PI3K-Akt pathway. However, the particular function of the PI3K-Akt axis in cervical cancer remains unclear. Mutations of PIK3CA in cervical cancer may be correlated with disease progression. Mutant PIK3CA may activate PI3K-AKT-mTOR and PIK3CA-E545K-SIRT4 signalling pathways, which in turn promotes cell propagation, invasion, and metastasis. Thus, the potential therapeutic approaches for targeting PIK3CA to treat cervical cancer have been studied, including several commercial inhibitors such as Buparlisib, Alpelisib, Dactolisib, etc. This review outlines the function of mutant PIK3CA and places special emphasis on the potential for targeting the PI3K-Akt axis as well as the effectiveness of PIK3CA inhibition as a treatment for cervical cancer. Clarification of the mechanism and clinical relevance of PIK3CA mutation-induced cervical cancer is still needed.

Diagnostic value of dynamic enhanced multi-slice spiral CT in lymph node metastasis of cervical cancer and analysis of the causes of missed diagnosis

Diagnostic value of dynamic enhanced multi-slice spiral CT in lymph node metastasis of cervical cancer and analysis of the causes of missed diagnosis

Orbital Metastasis of Cervical Squamous Cell Cancer during Treatment with Pembrolizumab

Purpose: This case report presents a rare occurrence of squamous cell carcinoma metastasizing to the orbit from the cervix.Case summary: A 48-year-old female with cervical cancer and multiple bone metastases experienced binocular diplopia two days prior to admission to the Department of Gynecology for scheduled chemotherapy. She was undergoing treatment with pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, for metastatic cervical cancer. The patient exhibited unilateral ptosis and restricted eyeball movement in the right eye. Brain MRI revealed a well-defined lobulated lesion attached to the superior rectus muscle in the right orbit and orbital apex. In suspicion of metastasis, radiation therapy with a dosage of 3,600 cGy was administered to the right orbital area, resulting in a reduction in size of the metastatic lesion. However, distant metastases subsequently developed in the bone and soft tissue, leading to the patient's demise one month later.Conclusions: This report emphasizes the importance of considering orbital metastasis from cervical cancer in patients undergoing advanced stage chemotherapy. It highlights the rarity of such cases and underscores the need for heightened awareness of this malignancy in patients with underlying cancer.

Selenium promotes immunogenic radiotherapy against cervical cancer metastasis through evoking P53 activation

Radiotherapy is still the recommended treatment for cervical cancer. However, radioresistance and radiation-induced side effects remain one of the biggest clinical problems. Selenium (Se) has been confirmed to exhibit radiation-enhancing effects for cancer treatment. However, Se species dominate the biological activities and which form of Se possesses better radiosensitizing properties and radiation safety remains elusive. Here, different Se species (the valence state of Se ranged from - 2, 0, +4 to + 6) synergy screen was carried out to identify the potential radiosensitizing effects and radiation safety of Se against cervical cancer. We found that the therapeutic effects varied with the changes in the Se valence state. Sodium selenite (+4) displayed strong cancer-killing effects but also possessed severe cytotoxicity. Sodium selenate (+6) neither enhanced the killing effects of X-ray nor possessed anticancer activity by its alone treatment. Although nano-selenium (0), especially Let-SeNPs, has better radiosensitizing activity, the - 2 organic Se, such as selenadiazole derivative SeD (-2) exhibited more potent anticancer effects and possessed a higher safe index. Overall, the selected Se drugs were able to synergize with X-ray to inhibit cell growth, clone formation, and cell migration by triggering G2/M phase arrest and apoptosis, and SeD (-2) was found to exhibit more potent enhancing capacity. Further mechanism studies showed that SeD mediated p53 pathway activation by inducing DNA damage through promoting ROS production. Additionally, SeD combined with X-ray therapy can induce an anti-tumor immune response in vivo. More importantly, SeD combined with X-ray significantly inhibited the liver metastasis of tumor cells and alleviated the side effects caused by radiation therapy in tumor-bearing mice. Taken together, this study demonstrates the radiosensitization and radiation safety effects of different Se species, which may shed light on the application of such Se-containing drugs serving as side effects-reducing agents for cervical cancer radiation treatment.

Clinical value of conventional magnetic resonance imaging combined with diffusion-weighted imaging in predicting pelvic lymph node metastasis of cervical cancer.

In cervical cancer (CC), the involvement of pelvis lymph nodes is a crucial factor for patients' outcome. We aimed to investigate the value of conventional magnetic resonance imaging (MRI) combined with diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) in predicting CC pelvic lymph node metastasis (PLNM). This retrospective study included CC patients who received surgical treatments. Surgical pathology results served as the gold standard for investigating the diagnostic performance of conventional MRI combined with DWI. We analyzed the association between tumor ADC and PLNM, as well as other pathological factors. The areas under the receiver operating characteristic curves (AUCs) for ADC in assessing PLNM and pathological factors were evaluated, and optimal cut-off points were obtained. A total of 261 CC patients were analyzed. PLNM patients had significantly lower tumor ADC (0.829 ± 0.144×10-3mm2/s vs. 1.064 ± 0.345×10-3mm2/s, p<0.0001), than non-PLNM CC. The agreement between conventional MRI combined with DWI and pathological results on PLNM diagnosis was substantial (Kappa=0.7031, p<0.0001), with 76% sensitivity, 94.31% specificity, and 90.8% accuracy. The AUC of tumor ADC was 0.703, and the optimal cut-off was 0.95×10-3 mm2/s. In multivariate analysis model 1, tumor ADC<0.95×10-3mm2/s was significantly associated with PLNM (OR, 2.83; 95%CI, 1.08-7.43; p= 0.0346) after adjusting for age and pathological risk factors. In multivariate analysis model 2, tumor ADC<0.95×10-3mm2/s (OR, 4.00; 95%CI, 1.61-9.89; p=0.0027), age<35 years old (OR, 2.93; 95%CI, 1.04-8.30; p=0.0428), increased tumor diameter on MRI (OR, 2.17; 95%CI, 1.18-3.99; p=0.0128), vaginal vault involvement on MRI (OR, 2; 95%CI, 1.002-3.99; p=0.0494) were independent predictors for PLNM. Tumor ADC<0.95×10-3mm2/s was significantly associated with higher risk of tumor diameter ≥4cm (OR, 2.60; 95%CI, 1.43-4.73; p=0.0017), muscular layer infiltration >1/2 (OR, 5.46; 95%CI, 3.19-9.34; p<0.0001), vaginal vault involvement (OR, 2.25; 95%CI, 1.28-3.96; p=0.0051), and lymphovascular space involvement (OR, 3.81; 95%CI, 2.19-6.63; p<0.0001). Conventional MRI combined with DWI had a good diagnostic performance in detecting PLNM. The tumor ADC value in PLNM patients was significantly lower than that in non-PLNM patients. Tumor ADC <0.95×10-3mm2/s, age <35 years old, increased tumor diameter on MRI, vaginal vault involvement on MRI were independent predictors for PLNM.

Magnolin targeting of the JNK/Sp1/MMP15 signaling axis suppresses cervical cancer microenvironment and metastasis via microbiota modulation

Magnolin (MGL), a compound derived from the magnolia plant, has inhibitory effects on tumor cell invasion and growth. His study aims to explore the antitumor effect and underlying molecular mechanism of MGL against human cervical cancer. We found that MGL inhibited the proliferation, migration, and invasiveness of cervical cancer cells in vitro and in vivo. The underlying mechanism was shown to involve MGL-induced inhibition of JNK/Sp1-mediated MMP15 transcription and translation. Overexpression of JNK/Sp1 resulted in significant restoration of MMP15 expression and the migration and invasion capabilities of MGL-treated cervical cancer cells. MGL modulated the cervical cancer microenvironment by inhibiting cell metastasis via targeting IL-10/IL-10 receptor B (IL-10RB) expression, thereby attenuating JNK/Sp1-mediated MMP15 expression. Analysis of the gut microbiota of mice fed MGL revealed a significant augmentation in Lachnospiraceae bacteria, known for their production of sodium butyrate. In vivo experiments also demonstrated synergistic inhibition of cervical cancer cell metastasis by MGL and sodium butyrate co-administration. Our study provides pioneering evidence of a novel mechanism by which MGL inhibits tumor growth and metastasis through the IL-10/IL-10RB targeting of the JNK/Sp1/MMP15 axis in human cervical cancer cells.

Amide proton transfer weighted combined with diffusion kurtosis imaging for predicting lymph node metastasis in cervical cancer

ObjectiveTo investigate the value of amide proton transfer weighted (APTw) combined with diffusion kurtosis imaging (DKI) in quantitative prediction of lymph node metastasis (LNM) in cervical carcinoma (CC). MethodsData of 19 LNM(+) and 50 LNM(−) patients with CC were retrospectively analyzed. 3.0 T MRI scan was performed before the operation, including APTw and DKI. After post-processing, quantitative magnetization transfer ratio asymmetric at 3.5 ppm [MTRasym (3.5 ppm)], mean kurtosis (MK), and mean diffusivity (MD) maps were obtained. The MTRasym(3.5 ppm), MK, and MD values were respectively measured by two observers, and intra-class correlation coefficients (ICC) were used to test the consistency of the results. The independent samples t-test or Mann-Whitney U test was used to compare the differences in the values of each parameter. The ROC curve was used to analyze the predictive performance of parameters with significant differences and their combination parameter. ResultsThe two observers had good agreement in the measurement of each data (ICC > 0.75). The MTRasym(3.5 ppm) and MK values of the LNM(+) group(3.260 ± 0.538% and 0.531 ± 0.202) were higher than those of the LNM(−) group(2.698 ± 0.597% and 0.401 ± 0.148) (P < 0.05), while there was no significant difference in MD values between the two groups(P > 0.05). The area under the curves (AUCs) of MTRasym(3.5 ppm), MK value, and MTRasym(3.5 ppm) + MK value were 0.763, 0.716, and 0.813, respectively, when predicting LNM status of CC. ConclusionAPTw and DKI can quantitatively predict LNM status of CC, which is of importance in clinical diagnosis and treatment.