RESUMEN
Background: Primary tracheal lymphoepithelioma-like carcinoma (LELC) is extremely rare, with only a few cases reported so far, and few studies have focused on the radiological features. This study aimed to investigate contrast-enhanced computed tomography (CECT) and positron emission tomography-computed tomography (PET-CT) presentations of primary tracheal LELC to improve diagnosis. Methods: A retrospective analysis was conducted on the clinical and imaging data of 13 patients with confirmed primary tracheal LELC between December 2013 and August 2022. We analyzed the radiological profiles of lesions on the CECT and PET-CT images. Results: In 92.3% (12/13) of the cases, primary tracheal LELC lesions predominantly occurred in the thoracic segment. They manifested as singular, wide-based, eccentric, irregular nodules, or exhibited mass-like thickening of the tracheal wall with invasive growth both internally and externally along the wall. The thickest dimension of the lesion ranged from 9 to 28 mm, affecting a length of 30.8±13.5 mm. Luminal stenosis was evident in all patients, with the narrowest point reaching a stenosis rate of 85%. Lesion margins were clear in 69.2% (9/13), indistinct in 23.1% (3/13), and unclear in 7.7% (1/13) of all cases. Among the patients, 92.3% (12/13) exhibited a relatively uniform density on CT plain scans, with a CT value of 44.5±7.8 Hounsfield units (HU). Enhancement scans revealed moderate to marked enhancement in 75% (9/12) of cases. In 2 cases undergoing PET-CT examination, lesion standardized uptake values (SUVs) were 4.4 and 5.1, whereas enlarged lymph node SUVs were 7.7 and 6.3, respectively. Mediastinal lymph node enlargement was observed in 8 patients (61.5%, 8/13), with a maximum short axis of 11.1±5.5 mm. After treatment, 9 out of 12 patients (75%) showed no evidence of distant metastasis upon CT re-examination. Conclusions: Early detection of primary tracheal LELC allows for curative resection and may lead to a favorable prognosis. It presents with characteristic CT findings, and the utilization of PET-CT improves diagnosis and staging.
RESUMEN
Small cell lung cancer (SCLC) is characterized by rapid development of chemoresistance and poor outcomes. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are widely used in breast cancer and other cancer types. However, the molecular mechanisms of CDK4/6 in SCLC chemoresistance remain poorly understood. Here, Rb1flox/flox, Trp53flox/flox, Ptenflox/flox (RTP) and Rb1flox/flox, Trp53flox/flox, MycLSL/LSL (RPM) spontaneous SCLC mouse models, SCLC cell line-derived xenograft (CDX) models, and SCLC patient-derived xenograft (PDX) models are established to reveal the potential effects of CDK4/6is on SCLC chemoresistance. In this study, it is found that CDK4/6is palbociclib (PD) or ribociclib (LEE) combined with chemotherapeutic drugs significantly inhibit SCLC tumor growth. Mechanistically, CDK4/6is do not function through the classic Retionblastoma1 (RB) dependent axis in SCLC. CDK4/6is induce impair autophagy through the AMBRA1-lysosome signaling pathway. The upregulated AMBRA1 protein expression leads to CDK6 degradation via autophagy, and the following TFEB and TFE3 nuclear translocation inhibition leading to the lysosome-related genes levels downregulation. Moreover, it is found that the expression of CDK6 is higher in SCLC tumors than in normal tissue and it is associated with the survival and prognosis of SCLC patients. Finally, these findings demonstrate that combining CDK4/6is with chemotherapy treatment may serve as a potential therapeutic option for SCLC patients.
RESUMEN
Neutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC.
RESUMEN
Tumor invasion and metastasis are the underlying causes of the high mortality rate of oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhanced cytochrome-c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In OSCC patient samples, expression of DAZAP1 positively correlated with COX16, and high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.