Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer最新文献

Iron is an essential trace element for the human body, but having too much or too little of it can cause various biological issues. When ferrous ions react with hydrogen peroxide, they create highly reactive and soluble hydroxyl radicals that can damage cells through oxidation. This reaction, known as the Fenton reaction, can cause lipid peroxidation and ferroptosis. Understanding how Fenton reaction-mediated ferroptosis works is crucial in treating rheumatoid arthritis (RA). Whether supplementing iron to induce ferroptosis or suppressing Fenton reaction-mediated ferroptosis is the key to regulating the pathophysiology of RA and cancer. Therefore, targeting ferroptosis regulators could be a promising new direction in developing therapeutic drugs for RA and cancer, which warrants further research.

Microplastics (MPs), pervasive environmental pollutants, have raised significant concerns regarding their potential impact on human health, particularly in relation to cancer. This review examines the current evidence linking MPs to various cancers, including ovarian, gastric, blood, brain, colorectal, lung, liver, breast, and cervical cancers. Recent studies indicate that MPs, including polystyrene nanoparticles (PS-NPs) and microplastics (PS-MPs), can exacerbate tumor progression through mechanisms such as oxidative stress, inflammation, and endocrine disruption. For instance, in ovarian cancer, PS-NP exposure has been shown to accelerate tumor growth, while in gastric cancer, PS-MPs alter gene expression to promote cancer progression. Blood cancer research highlights the presence of MPs in human blood, suggesting their potential systemic distribution and impact. MPs' ability to cross the blood-brain barrier raises concerns about brain cancer, where they may induce neurotoxicity. Similarly, MPs contribute to colorectal cancer by causing intestinal inflammation and gut microbiota alterations. Inhalation of MPs is linked to lung cancer due to chronic inflammation and oxidative stress. In liver cancer, MPs induce hepatic toxicity and promote carcinogenesis. Breast and cervical cancers are associated with MPs endocrine-disrupting properties, leading to increased cell proliferation and migration. This review underscores the urgent need for further research to elucidate the mechanisms through which MPs contribute to cancer and to inform public health strategies and regulatory policies aimed at mitigating the risks of microplastic exposure.

Expression and functional dysregulation of ion channel genes are correlated with an unfavorable prognosis in lung adenocarcinoma (LUAD). Ion channel signature for predicting the prognosis of individuals with LUAD. 94 ion channel-related differentially expressed genes in LUAD were identified from TCGA-LUAD, and ion channel-based LUAD risk model was established and validated using the GEO cohort. Survival analysis outcomes demonstrated that low-risk LUAD patients were accompanied with higher survival rates. Cox analysis manifested that LUAD prognostic risk score was an independent prognosticactor. We plotted a nomogram with clinical utility based on LUAD risk score and clinical factors. Differentially expressed genes in LUAD patients of different risk groups were enriched in biological functions and signaling pathways related to ion channels, cancer transcription dysregulation, and immunity. Immune infiltration results suggested that LUAD patients with low risk scores exhibited better immune cell infiltration and function. Prediction results of immunotherapy response showed that LUAD patients with low risk scores had a higher chance of benefiting from immunotherapy. The drug prediction results showed that individuals with LUAD in the low-risk group were more sensitive to paclitaxel, BI 2536, pyrimethamine, and VX-680, while individuals with LUAD in the high-risk group to erlotinib, sorafenib, panitumumab, PHA-665752, and roscovitine. In summary, ion channel-related genes can provide valuable information for prognosis assessment and drug treatment of LUAD patients.

Background: Lung adenocarcinoma (LUAD) is one of the most malignant tumors with significant implications for population health and life. Nicotinamide metabolism may play a pivotal part in influencing the prognosis of LUAD. This study aimed to figure out the potential value of nicotinamide metabolism-related genes (NMRGs) in LUAD prognosis.

Methods: Forty-two NMRGs were obtained from the Molecular Signatures Database and intersected with differentially expressed genes (DEGs) in LUAD from The Cancer Genome Atlas. Unsupervised consensus clustering was conducted based on the intersecting genes, followed by identification of DEGs between clusters. Enrichment analyses and LASSO-Cox regression analyses were conducted. Immune cell infiltration was calculated using the ssGSEA algorithm. Wilcoxon test was conducted on the TIDE scores of different risk groups. Targeted small molecule drug prediction was performed on the DEGs in groups.

Results: A total of 10 nicotinamide metabolism-related differentially expressed genes (NMRDEGs) were identified for LUAD clustering. LUAD patients were divided into two clusters. Cluster 1 had considerably higher overall survival rates compared to cluster 2. Differential genes between clusters were mainly enriched in hormone metabolic processes and the neuroactive ligand-receptor interaction pathway. An 11-gene prognostic model was established to predict the overall survival of LUAD patients. The validation set showed that the model had a good prognostic effect. Analysis of immune cell infiltration demonstrated that in the high-risk (HR) group, infiltration levels of mast cells and neutrophils were considerably lower than low-risk (LR) group, while infiltration levels of NK cells and Th2 cells were considerably higher than LR group. TIDE scores indicated a lower likelihood of immune evasion and a potentially better response to immunotherapy in LR patients. Drug prediction showed that FGIN-1-43, deferiprone, and griseofulvin were potential drugs.

Conclusion: We successfully developed a predictive model for the survival and immunotherapy response of LUAD patients.

Cholangiocarcinoma (CCA) is a life-threatening malignancy, and there is an urgent need for new biomarkers to improve the prognosis of patients. The expression of ELF3 in CCA tumor and non-tumor tissues was examined in two cohorts. ELF3 expression and the methylation level of its promoter in CCA patients with various clinicopathological features were analyzed using the UALCAN website. Co-expressed genes significantly associated with ELF3 were screened using the LinkedOmics website. A protein-protein interaction (PPI) network for these co-expressed genes was constructed using the STRING website. Core co-expressed genes correlated with ELF3 were identified through random walk with restart (RWR) analysis. GeneMANIA was utilized to analyze the major biological functions within networks of kinases and TFs mediated by ELF3. Potential targeted drugs for CCA treatment were screened using the Connectivity Map (CMAP) database. ELF3 expression in CCA tissue was significantly increased compared with that in normal tissue. Among CCA patients with distinct clinicopathological features, ELF3 expression was notably elevated in tumor tissues compared to normal tissue, while ELF3 promoter's methylation levels in tumor tissue were significantly decreased. In total, 307 co-expressed genes, evidently relevant to ELF3, were identified through LinkedOmics analysis. RWR analysis revealed 61 co-expressed genes closely associated with ELF3. Enrichment analysis indicated that these genes control cell junctions and epithelial cell differentiation. GeneMANIA analysis uncovered that ELF3-involved regulatory networks of kinases and TFs were primarily linked to the regulation of immune cells and cell adhesion. CMAP analysis identified 10 potential small molecules for CCA treatment including 4 existing drugs used for other diseases. ELF3 shows promise as a diagnostic marker for CCA, and the drugs we have identified hold great potential for the treatment of this fatal disease.

Invasive ductal carcinoma (IDC) is a major type of breast cancer. The utilization of inhibitors targeting histone methyltransferases introduces novel therapeutic avenues for the treatment of cancer. Immunohistochemistry, Western blot, and reverse transcription quantitative polymerase chain reaction experiments were applied to assess the levels of EHMT2 in IDC and adjacent tissues. HCC70 cells were treated with EHMT2 inhibitors (UNC0646 and BIX-01294), and assessed using Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and transwell assays to evaluate cell viability, apoptosis, and migratory capacity, respectively. The reactive oxygen species (ROS) levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The expressions of Hippo pathway were analyzed via Western blot assay. Immunofluorescence staining was employed to detect the subcellular localization changes in YAP expression. A xenograft tumor model of HCC70 cells was applied to validate the tumor-suppressive influences of EHMT2 inhibitors in vivo. We observed significant upregulation of EHMT2 in both IDC clinical samples and IDC cell lines, with high EHMT2 expression correlating with poor prognosis. After treatment with EHMT2 inhibitors UNC0646 or BIX-01294, HCC70 cells exhibited inhibition of proliferation and migratory capacity, alongside an increase in apoptosis rate and ROS production levels. UNC064 or BIX-01294 promoted the phosphorylation levels of MST1, LATS1, MOB1A, and YAP, indicating the activation of the Hippo pathway by EHMT2 inhibitors. Moreover, UNC0646 and BIX-01294 enhanced the cytoplasmic expression of YAP while inhibiting its nuclear localization, preventing its nuclear activation. EHMT2 was upregulated in IDC, and EHMT2 inhibitors suppressed IDC progression by modulating the Hippo signaling pathway.

Breast cancer (BC) is one of the main causes of cancer-related death in women. The purpose of this study was to evaluate the expression of miR-605-5p in BC and its diagnostic and prognostic value. BC patients and healthy individuals who met the study criteria were included. Real-time fluorescence quantitative PCR (RT-qPCR) was used for the detection of miR-605-5p expression in BC patients and BC cell lines. The ROC curve was used for the assessment of the diagnostic value of miR-605-5p. The Kaplan-Meier survival curve was used to assess the prognostic value of miR-605-5p. CCK-8 and Transwell assays were performed to detect the effect of miR-605-5p on BC cell activity. The results of this study showed that miR-605-5p was markedly downregulated in BC and correlated with the clinicopathological features of the patients. The expression level of miR-605-5p has high diagnostic accuracy for distinguishing BC patients from healthy individuals. Low expression predicts an unfavorable prognosis for BC patients, while up-regulation of miR-605-5p inhibited the activity of BC cells. In summary, miR-605-5p has the potential to serve as an important molecular marker for prognostic analysis and prediction of BC patients.