Pim-1 (Provirus integration site for Moloney murine leukemia virus 1) belongs to the Ser/Thr kinase family and plays a pivotal role in occurrence and development of oncogenesis. Recent studies have demonstrated that Pim-1 phosphorylates RUNX3 and alters its subcellular localization. However, few studies have concerned the implications of Pim-1 in the salivary gland adenoid cystic carcinoma (ACC). In this study, we aimed to clarify the function of Pim-1 in ACC in vitro. Meanwhile, we measured the levels of Pim-1 and RUNX3 in the ACC tissues. The correlations between Pim-1/RUNX3 levels and clinical parameters were also analyzed. SACC-83 and SACC-LM cells were transfected with the Pim-1 siRNA. Pim-1 mRNA and protein expression were measured using real-time PCR and immnuoblot, respectively. Cell proliferation was analyzed by CCK-8 assay. Cell cycle, apoptosis, and mitochondrial membrane potential were detected by flow cytometry. Effects of Pim-1 on cells’ invasion were evaluated by transwell migration assay. Pim-1 and RUNX3 levels in ACC tissues were examined by immunohistochemistry. Pim-1 siRNA reduces cell proliferation, induces apoptosis, causes cell cycle arrest through cell cycle related proteins (Cyclin D1 and CDK4), mitochondrial depolarization, and decreases invasive ability in SACC-83 and SACC-LM cells. Pim-1 and RUNX3 levels are significantly relevant and associated with T-stage and nerve invasion in the ACC tissues. This study demonstrates the oncogenic role of Pim-1 in ACC. The findings also suggest that Pim-1 may serve as a neoteric therapeutic target and potential prognostic marker for ACC cancer.

This study aims to evaluate candidate risk factors for lateral lymph node metastasis (LLNM) and develop a predictive model to identify high-risk groups among patients with papillary thyroid carcinoma (PTC). Additionally, we identified risk factors for recurrence to inform postoperative therapeutic decisions and follow-up for physicians and patients. A total of 4107 patients (4884 lesions) who underwent lymph node dissection at our hospital from 2005 to 2014 were evaluated. LLNM risk was stratified, and a risk-scoring model was developed based on identified independent risk factors for LLNM. Cox’s proportional hazards regression model was used to investigate the risk factors for recurrence. Lateral Lymph Node (LLN) metastasis was observed in 10.49% (431/4107) of patients. Multivariate analysis identified the following independent risk predictors for LLN metastasis: Age ≤ 35 years (P = 0.002), tumor size > 1.0 cm (P = 0.000), lobe dissemination (+) (P = 0.000), and CLNM (+) (P = 0.000). A 12-point risk-scoring model was constructed to predict stratified LLNM in PTC patients, with an area under the receiver operating characteristic curve (AUROC) of 0.794 (95% CI: 0.774–0.814) (P < 0.01). The Cox regression model indicated that tumor size > 1.0 cm, lobe dissemination (+), multifocality, Central Lymph Node Metastasis (CLNM), and LLNM were significant risk factors associated with poor outcomes. Based on the risk scoring model, additional investigations and comprehensive considerations are recommended for patients with a total score greater than 5, and prophylactic cervical lymph node dissection is performed if necessary. Additionally, more aggressive treatment and more frequent follow-ups should be considered for patients with tumor size > 1.0 cm, lobe dissemination (+), multifocality, CLNM, and LLNM.

Ferroptosis-induced therapy is a promising approach for treating anaplastic thyroid carcinoma (ATC), a highly lethal form of cancer. However, the specific effects of two anti-angiogenic agents, lenvatinib and anlotinib, on ferroptosis in ATC are not well understood. Methods: To investigate the anticancer activity of lenvatinib and anlotinib in vivo, a subcutaneous tumor model was established in mice. The pharmacological effects of these agents on ATC cells were assessed using various assays, including CCK-8, colony formation, transwell, and sphere-forming assays. Angiogenesis was evaluated using a tubule formation assay. Reactive oxygen species (ROS) levels were measured by flow cytometry, and levels of ferroptosis and endoplasmic reticulum (ER) stress were determined through western blot assays. Immunohistochemistry analyses were used to profile the expression of GPX4, HO-1, PERK, and CHOP in tumor tissues. Both lenvatinib and anlotinib demonstrated dose- and time-dependent inhibition of Luciferase-8505 C-induced subcutaneous tumors in mice, with anlotinib showing greater efficacy than lenvatinib. In vitro experiments revealed that while both drugs were effective at inhibiting angiogenesis, anlotinib displayed superior antitumor effects in terms of cell viability, proliferation, tumor sphere formation, migration, and invasion. Mechanistic studies indicated that anlotinib induced ROS-mediated ferroptosis through the ER stress pathway, a response not observed with lenvatinib treatment. Anlotinib showed superior efficacy in treating ATC compared to lenvatinib, independent of their anti-angiogenic properties. The ability of anlotinib to induce ER stress-mediated ferroptosis suggests that targeting ferroptosis may hold promise as a therapeutic strategy for ATC.

Increasing evidence suggests that disulfidptosis plays a crucial role in tumorigenesis and progression. This study aimed to identify biomarkers closely associated with disulfidptosis in anaplastic thyroid carcinoma (ATC). Utilizing ATC-related datasets (GSE65144, GSE9115, GSE27155, and GSE53072) in conjunction with disulfide bond-related genes (DRGs) identified in the literature, differentially expressed genes (DEGs) were screened from the GSE65144 and GSE9115 datasets. A total of 113 common DEGs were identified through cross-sectional analysis. Weighted gene co-expression network analysis (WGCNA) was employed to screen genes related to disulfidptosis and ATC, and five biomarkers—ATP1B3, TFF3, LGALS1, ADAM12, and COL1A2—were identified using machine learning algorithms. A nomogram model constructed based on these markers demonstrated high accuracy. In vitro validation revealed that ATP1B3 knockdown significantly inhibited tumor growth, indicating its potential anti-ATC activity. Furthermore, laser confocal microscopy, flow cytometry, and other experimental methods suggested a correlation between ATP1B3 and disulfidptosis. These findings highlight ATP1B3, TFF3, LGALS1, ADAM12, and COL1A2 as potential disulfidptosis-related biomarkers in ATC. This study provides a theoretical foundation for understanding the role of disulfidptosis in ATC pathogenesis and suggests that ATP1B3 may serve as a promising therapeutic target.