Cancer Cell International最新文献

Gliomas represent one of the most common types of primary brain tumor. Due to their poor prognosis and propensity for recurrence, new therapeutic targets are urgently required. A consensus is emerging that there is a significant relationship between tumor formation and embryonic development. However, the precise mechanisms and regulatory targets remain unclear. A variety of bioinformatics techniques, including GSVA, differential expression analysis, machine learning algorithms and others, were employed to elucidate the significance of germ layer development (GLD) in glioma and identify MEST as the key gene. To validate the results, in vivo and in vitro experiments were conducted, including tumor xenografts, RT-qPCR, immunocytofluorescence, transwell assays and others, which confirmed the central role of the selected oncogenic gene. Here, we performed a comprehensive bioinformatics analysis of GLD genes, providing a novel insight into the landscape of the GLD in gliomas, and confirmed the GLD-related gene MEST as a key oncogenic therapeutic target via machine learning feature selection framework. Furthermore, we have identified the core gene MEST and have conducted extensive research to elucidate its pivotal role in glioma progression through in vivo and in vitro experiments. We leveraged the GLD patterns in glioma and found that the MEST might promote the glioma development through activating RAS signaling and Wnt signaling.

Background: Oral cancer (OC) is the most common type of head and neck cancer, with a high mortality rate, and is a leading cause of cancer-related deaths worldwide. Drug-induced ferroptosis is a novel form of non-apoptotic cell death that offers a promising strategy for cancer therapy. Accumulating evidence has emphasized the significant role of methotrexate (MTX) in the treatment of many malignancies; however, its role in the ferroptosis pathway in OCs and its underlying mechanisms remain poorly understood.

Methods: After treating the OC cells with MTX, several cellular function assays were performed, including cell proliferation, apoptosis, colony formation, and wound healing assays. Distinctive features of ferroptosis were detected, and qPCR and western blot (WB) assays were performed to validate the expression of genes and proteins related to ferroptosis pathways in MTX-treated cells. In vitro experiments were conducted to further explore the mechanisms by which MTX regulates the stability of nuclear factor erythroid 2-related factor 2 (NRF2) in OC cells. Finally, in a mouse model using MOC1 cells, some experiments were performed to demonstrate MTX-induced ferroptosis and tumor suppression.

Results: In this study, based on in vitro and in vivo experiments, we found that MTX significantly reduced OC cell viability by inducing ferroptosis. Mechanistically, MTX administration increased the phosphorylation of Kelch-like ECH-associated protein 1 (KEAP1) at threonine 43 via activation of the ERK/MAPK signaling pathway, thereby maintaining the protein complex formed by KEAP1 and NRF2. As result of the decreased NRF2 expression, the levels of SLC7A11 and GPX4 proteins were markedly suppressed in MTX-treated OC cells, ultimately leading to the induction of ferroptosis in OC.

Conclusions: Our data demonstrated that MTX-mediated activation of the ERK/KEAP1 signaling pathway significantly induced ferroptosis by inhibiting the NRF2/HO-1/SLC7A11/GPX4 axis, thereby suppressing OC progression. These findings suggest that MTX is a promising candidate for OC treatment, offering a meaningful and effective therapeutic-strategy.

Protein tyrosine phosphatase receptor-type O (PTPRO), a member of the PTP family, has garnered attention for its diagnostic and prognostic potential through the methylation of circulating tumor DNA (ctDNA). However, the utility of ctDNA has shown limited sensitivity and specificity, particularly in early-stage lung adenocarcinoma (LUAD). Given the enhanced stability of tumor-derived DNA in small extracellular vesicles (sEVs) from cancer cells, this research investigates the feasibility of using PTPRO methylation in saliva-derived sEVs as a non-invasive and easily accessible biomarker for the early detection of LUAD. To explore the relationship between PTPRO methylation and prognosis in early-stage LUAD, we conducted Kaplan-Meier survival analyses and assessed the methylation status of the PTPRO promoter using methylation-specific PCR (MSP) and q-MSP. Saliva samples were collected from 60 early-stage LUAD patients, 30 pneumonia patients, and 21 healthy controls, with isolation and characterization of salivary sEVs through transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and immunoblotting. Kaplan-Meier analysis revealed hypermethylation of PTPRO was linked to poorer overall survival in early-stage LUAD patients. PTPRO methylation was detected in salivary sEVs of 73.3% of early-stage LUAD patients, compared to only 35% in plasma sEVs. Receiver operating characteristic (ROC) analysis confirmed that PTPRO methylation in salivary sEVs effectively distinguished early-stage LUAD patients from both pneumonia patients and healthy individuals. This suggests that PTPRO hypermethylation is associated with adverse prognosis in early-stage LUAD. The detection of PTPRO methylation in salivary sEVs demonstrates high sensitivity and specificity, indicating its potential as an epigenetic biomarker for the non-invasive diagnosis of early-stage LUAD.

Leukemia survivorship presents ongoing clinical and functional challenges, including persistent fatigue, metabolic disturbances, and reduced quality of life. Integrative, non-pharmacologic strategies that combine exercise and targeted nutrition may help address these late effects. This narrative review synthesizes current evidence on the physiological, molecular, and clinical impact of exercise training and nutritional interventions among leukemia survivors. Exercise programs, ranging from aerobic and resistance training to high-intensity interval and mobile health-based formats, consistently improve cardiorespiratory fitness, muscular strength, and fatigue outcomes, while modulating inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. Nutritional components including polyphenol-rich functional foods, omega-3 fatty acids, and microbiota-supportive diets contribute anti-inflammatory and antioxidant effects that may complement exercise in restoring immune and metabolic balance. Together, these approaches form a promising foundation for personalized supportive care in leukemia survivorship. Yet, most studies remain limited by small sample sizes, heterogeneous protocols, and short follow-ups. Future research should prioritize larger, leukemia-specific clinical trials integrating exercise and nutrition components, with standardized outcome measures to enable evidence-based recommendations for survivorship care.