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

Prostate cancer and inflammation mechanism are closely related because chronic inflammation causes inflammatory cells to infiltrate into prostatic atrophy areas and proliferative inflammatory atrophy is accepted as the initiator of prostate cancer. The study included 90 patients (28 patients with benign prostatic hyperplasia (BPH), 35 patients with localized prostate cancer (LPCa), and 27 patients with metastatic prostate cancer (MPCa) and 90 healthy controls. Blood samples from 90 patients and 90 healthy people were used to isolate genomic DNA. Serum protein levels were detected using the ELISA technique, and genotyping was done using the PCR-RFLP method. It was found that genotype distributions of CCR3 gene rs4987053 and the COX-2 gene rs689466 variants showed a substantial difference between the groups (Control, BPH, LPCa, MPCa) (respectively P < 0.05, P < 0.001). In addition, a important difference was determined between the non-cancerous and the prostate cancer groups in the NOD1 gene rs5743336 variant genotype distributions (P < 0.05). However, no substantial relationship was determined between the rs16969415, rs1801157, rs2228014, rs2066847, rs4986791 variants, and a risk of prostate cancer. The serum IL-1β, LY96, and TLR4 protein levels differed significantly between the groups (Control, BPH, LPCa, MPCa) (P < 0.001). In addition, IL-1β was associated with rs689466, LY96 with rs2228014, rs5743336 genotypes (P < 0.05). As a conclusion, the CCR3 gene rs4987053, COX-2 gene rs689466, and NOD1 gene rs5743336 variations were determined to be closely associated with prostate cancer risk.

Targeting PI3K/AKT/MTOR (PAM) signaling pathway may be a strategy at the fore for treating lung squamous cell carcinoma (LUSC). However, relationships of PAM pathway-related genes (PAGs) with LUSC prognosis are unknown. Therefore, identifying the prognostic significance of PAGs for LUSC is innovative and feasible. Transcriptomic data, clinical features, and PAGs of LUSC were obtained from public databases (TCGA, GEO). A PAGs-based prognostic model was built using regression analysis in TCGA-LUSC. Gene levels were assessed via qRT-PCR. Predictive performance was verified through multiple datasets. Differences in immune infiltration and anti-tumor immunity between risk groups were assessed by R packages. Sensitivity to common anti-cancer agents was tested using oncoPredict package. We identified a Riskscore model containing 11 PAGs. Patients were assigned into groups of high risk (HR) and low risk (LR) per median Riskscore. CAB39L, CDKN1A, and ITPR2 were significantly underexpressed in LUSC cells. TRAF2 and TRIB3 were significantly enhanced in LUSC cells. The LR group had a longer survival time. Prognostic values of one-, three-, and five-year ROC curves were good. Results were verified in GEO. Patients in LR group had higher immune infiltration levels of B cells and Tfh cells, and higher ssGSEA scores for APC_co_inhibition and T_cell_ co_stimulation. LR group had lower TIDE scores and lower IC50 values (Alpelisib, Ibrutinib, Sapitinib, and Savolitinib). We successfully built a reliable 11-gene Riskscore prognostic model. Patients in LR group had potential advantages in survival, immune response, and drug sensitivity. In summary, the results offered new insights into prognosis prediction, immunotherapy, and personalized treatment of LUSC.

Colorectal cancer (CRC) is a malignant tumor that affects patients worldwide, and its mortality rate is high. Although treatments that activate TNF-associated apoptosis-inducing ligand (TRAIL)-induced apoptosis have shown some efficacy, many CRC patients are resistant to TRAIL therapy. Our findings indicated that the lncRNA PTCSC1 is over-expressed in CRC. However, the mechanism underlying resistance to PTCSC1 in CRC is unclear. In this work, we determined the role of PTCSC1 in TRAIL-resistant CRC patients and explored possible molecular mechanisms. We found that TRAIL-sensitive HCT116 and SW480 cells expressed relatively lower levels of PTCSC1 than TRAIL-resistant HT-29 and caco-2 cells. Increased expression of PTCSC1 was here found to inhibited TRAIL-induced apoptosis in HCT116 and SW480 cells. Decreased expression of PTCSC1 increased TRAIL-induced apoptosis in HT-29 and caco-2 cells. The level of expression of PTCSC1 was related to their sensitivity to TRAIL-induced apoptosis. Furthermore, PTCSC1 decreased the expression of Death Receptor 4 (DR4) while increased the activation of serine/threonine kinase 1 (AKT) and Forkhead Box O3a (FOXO3a). Our findings therefore support the idea that targeting PTCSC1 function may represent a strategy to overcome TRAIL resistance in CRC through the DR4/AKT/FOXO3a pathway.

Numerous genes have been associated with colorectal cancer (CRC) treatment in prior studies, but the impact of radiotherapy-related autophagy genes (RRAGs) on CRC remains largely unexplored. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were implemented to screen out RRAGs significantly associated with survival, and a prognostic model was constructed. Samples were categorized into high- and low-risk groups with median riskscore. Immunomicroenvironment analysis, immunotherapy response prediction, enrichment analysis, tumor mutation analysis and drug prediction were performed in risk groups. Expression of signature genes in CRC cells was examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). There were 10 CRC-related RRAGs found. Prognostic models were built with RRAGs. Based on immune infiltration analysis, low-risk populations showed significantly greater levels of immune infiltration (P P ARHGEF17 mutation rate was 6%. Medications such as CGP-082996, Dasatinib, Erlotinib, and Salubrinal were more sensitive to high-risk group, whereas drugs such as FTI-277, DMOG, and Crizotinib were more sensitive to low-risk group. UGT1A6 and IRGM were significantly upregulated in tumor group as revealed by qRT-PCR. This study constructed a new prognostic model for CRC patients based on RRAGs, and a series of analysis results is conducive to providing more theoretical references and new insights into precision treatment of CRC patients.

Despite advancements in systemic therapy, the mortality rate for patients with metastatic melanoma remains around 70%, underscoring the imperative for alternative treatment strategies. Through the establishment of a chemoresistant melanoma model and a subsequent drug investigation, we have identified pacritinib, a medication designed for treating myelofibrosis and severe thrombocytopenia, as a potential candidate to overcome resistance to melanoma therapy. Our research reveals that pacritinib, administered at clinically achievable concentrations, effectively targets dacarbazine-resistant melanoma cells by suppressing IRAK1 rather than JAK2. Notably, melanoma-resistant cells exhibit elevated p-IRAK1 levels, while there is no discernible difference in p-JAK2 levels between sensitive and resistant cells. Additionally, analysis of melanoma patients indicates a higher expression of IRAK1, correlating with a significantly improved survival rate. Furthermore, the depletion of IRAK1 not only reduces cell viability in melanoma cells but also enhances the effectiveness of dacarbazine treatment. In a dacarbazine-resistant melanoma model, pacritinib demonstrates significant inhibition of tumor growth in mice, leading to enhanced overall survival. In the dacarbazine-sensitive melanoma model, the combination of pacritinib and dacarbazine is more effective than dacarbazine alone in reducing tumor growth and improving overall survival in mice. In summary, our findings highlight IRAK1 as a promising therapeutic target to overcome melanoma resistance, and pacritinib emerges as a valuable addition to the treatment armamentarium for melanoma.

Neuro-oncology is the study of brain and spinal cord neoplasms. Molecular targets and signaling pathways are pivotal in advancing modern healthcare, particularly in personalized medicine. Signaling pathways, which regulate cellular processes such as growth, division, and survival, are frequently dysregulated in cancer. Targeting these pathways has enabled the development of personalized therapies that improve efficacy while minimizing side effects. This approach has led to significant improvements in patient outcomes, reduced treatment toxicity, and a shift toward precision medicine, driving innovation in drug discovery. The integration of molecular targets and signaling pathways into clinical practice highlights their importance for enhancing patient care.

Background: This study was to screen for circRNAs associated with osimertinib resistance in lung adenocarcinoma (LUAD) and establish a circRNA-miRNA-mRNA ceRNA network.

Methods: DESeq2 analysis was used to identify circRNAs in GEO database associated with osimertinib resistance in LUAD. Differentially expressed miRNAs in LUAD intersected with the target miRNAs of circRNA. Predicted target gene for miRNAs were overlapped with the co-expressed genes of EGFR. Hsa_circ_0078465/miR-183-5p/NRAS axis was validated in cells.

Results: Osimertinib resistance-related circRNAs in LUAD were linked to six differentially expressed miRNAs and 35 EGFR-related mRNAs. NRAS was the hub gene. These mRNAs were associated with cell motility regulation, non-small cell lung cancer and EGFR tyrosine kinase inhibitor resistance pathway. The cell proliferation and migration assays confirmed the promoting role of hsa_circ_0078465/miR-183-5p/NRAS axis in osimertinib-resistant cells.

Conclusion: A circRNA-miRNA-mRNA network associated with osimertinib resistance in LUAD proposed hsa_ circ_0078465/miR-183-5p/NRAS axis.

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.