Objective To observe the value of radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced hepatobiliary phase(HBP)MRI for assessing clinical pathological stage of hepatic fibrosis(HF).Methods Data of 240 patients with pathologically/clinically diagnosed and clinical pathological staged HF who underwent Gd-EOB-DTPA enhanced MR examination were retrospectively analyzed.The liver-to-muscle signal intensity ratio(SIR1)and liver-to-spleen signal intensity ratio(SIR2)were measured based on HBP images.Radiomics features of HBP images were extracted and screened to construct radiomics models.The signal intensity ratio(SIR)-radiomics combined models were constructed based on SIR and radiomics signatures.Receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of each model for assessing clinical pathological stage of HF.Results The area under the curve(AUC)of SIR1 and SIR2 models for assessing clinical pathological stage of HF were 0.63-0.70 and 0.65-0.71,respectively.The most effective radiomics model for assessing HF,significant HF,advanced HF and early cirrhosis was support vector machine(SVM),SVM,light gradient boosting machine and K-nearest neighbor model,respectively,with the AUC in validation set of 0.87,0.82,0.81 and 0.80,respectively,while the AUC of SIR-radiomics combined models in validation set of 0.88,0.82,0.82 and 0.81,respectively.Conclusion The radiomics models based on Gd-EOB-DTPA enhanced HBP MRI were helpful for assessing clinical pathological stage of HF.Combining with HBP SIR could improve their efficacy.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF) plays dual roles in the initiation and development of human malignancies. However, the biological role of SPDEF in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC, GSE65858, and our own clinical cohorts. CCK8, colony formation, cell cycle analysis, and a xenograft tumor growth model were used to determine the molecular functions of SPDEF in HNSCC. ChIP-qPCR, dual luciferase reporter assay, and rescue experiments were conducted to explore the potential molecular mechanism of SPDEF in HNSCC. Compared with normal epithelial tissues, SPDEF was significantly downregulated in HNSCC tissues. Patients with HNSCC with low SPDEF mRNA levels exhibited poor clinical outcomes. Restoring SPDEF inhibited HNSCC cell viability and colony formation and induced G0/G1 cell cycle arrest, while silencing SPDEF promoted cell proliferation in vitro. The xenograft tumor growth model showed that tumors with SPDEF overexpression had slower growth rates, smaller volumes, and lower weights. SPDEF could directly bind to the promoter region of NR4A1 and promoted its transcription, inducing the suppression of AKT, MAPK, and NF-κB signaling pathways. Moreover, silencing NR4A1 blocked the suppressive effect of SPDEF in HNSCC cells. Here, we demonstrate that SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 in HNSCC. Our findings provide novel insights into the molecular mechanism of SPDEF in tumorigenesis and a novel potential therapeutic target for HNSCC.
Carcinogenesis ; Cell Proliferation ; Head and Neck Neoplasms ; Humans ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Proto-Oncogene Proteins c-ets ; Squamous Cell Carcinoma of Head and Neck ; Transcription Factors

Gene therapy has been considered as a promising method for treatment of many diseases, such as acquired and genetic diseases. At present, there are two major vehicles for gene delivery including viral vectors and nonviral vectors. Viral vectors appear as high gene transfection efficiency, but some deficiencies such as inflammatory responses, recombination and mutagenesis have limited their use. On account of low pathogenicity, safety and cost-effectiveness, nonviral vectors have been attracted much attention. Cationic polymers are one of the nonviral vectors which have been widely studied. This review focuses on the structure of the cationic polymers and the interaction mechanism between the vector and DNA. We try to provide a framework for the future design and synthesis of nonviral vectors with high transfection efficiency and low toxicity for gene therapy.
Cations ; chemistry ; DNA ; genetics ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; Polymers ; chemistry