Journal of Cancer最新文献

Developing new drug delivery systems is crucial for enhancing the efficacy of oncolytic virus (OV) therapies in cancer treatment. In this study, mesenchymal stem cell (MSC)-derived vesicles and oncolytic viruses are exploited to construct a novel formulation. It has been hypothesized that vesicle-coated OVs could amplify cytotoxic effects through superior internalization by tumor cells. MSC vesicles possess natural tumor homing ability and biocompatibility, which can enhance the targeting, uptake, and therapeutic effects of OVs on tumor cells. Experimental results indicated that this treatment system has increased the apoptosis of tumor cells. Furthermore, flow cytometry analysis demonstrated that the uptake of tumor cells by OVs coated with MSC vesicles soared away compared to uncoated OVs, being 1.5 times than that of the uncoated group. Additionally, the confocal laser scanning microscopy also showed that the fluorescence intensity within tumor cells pretreated with MSC-coated OVs was greater. Meanwhile, propidium iodide (PI) staining revealed that MSC-coated Ovs exposed to tumor cells accelerating the apoptosis of the latter. According to the statistics, the number of dead cells was increased, and the flow cytometry testified that the apoptosis in the MSC-coated OV group was as high as 23.78%. These findings highlight the potential of MSC vesicle-coated OVs in enhancing the delivery and efficacy of oncolytic virus therapy, providing a promising strategy for cancer treatment.

The pathogenesis of metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma (MASLD-HCC) is complex and exhibits sex-specific differences. Effective methods for monitoring MASLD progression to HCC are lacking. Transcriptomic data from liver tissue samples sourced from multiple public databases were integrated. Utilizing both differential expression analysis and robust rank aggregation analysis, differentially expressed genes (DEGs) in patients with MASLD-HCC were identified. Based on these DEGs, diagnostic prediction models for MASLD (DP.MASLD) and HCC (DP.HCC) were constructed using elastic net analysis for various comparisons, including steatosis versus normal, steatohepatitis versus steatosis, and cancer versus non-cancer. Weighted gene correlation network analysis and gene set enrichment analysis were conducted to unveil the underlying pathogenesis of MASLD-HCC in males. Five overlapping DEGs with diagnostic significance in the progression from MASLD to HCC were identified, namely, AKR1B10, CYR61, FABP4, GNMT, and THBS1. DP.HCC demonstrated excellent predictive accuracy, with an area under the curve of 0.910 in the training group and 0.981 in the validation group. Similarly, DP.MASLD showed robust predictive accuracy. The pathogenesis of MASLD-HCC in males primarily involves extracellular matrix-receptor interaction, DNA replication, cell cycle, and T-cell receptor signaling. Overall, our study provides a quantitative assessment tool for the early detection and monitoring of MASLD-HCC, highlighting the male-specific molecular characteristics involved in its progression.

[This corrects the article DOI: 10.7150/jca.39671.].

Growth arrest specific 2 (GAS2) is a microfilament-associated protein, which is widely distributed in human tissues. It exerts a pivotal influence on various cellular processes, including cytoskeletal regulation, cell cycle progression, apoptosis, and senescence. GAS2 has a dual function in cancer cell growth: on the one hand, it enhances the sensitivity of cancer cells to chemoradiotherapy and prevents malignant transformation of normal cells; but on the other hand, it maintains the growth of cancer cells. GAS2 regulates the cellular activity of Calpain-2, a calcium-dependent protease, by acting as an endogenous inhibitor of the enzyme. The N-terminus of GAS2 binds to Calpain-2, while its C-terminus acts as an inhibitor of the protease activity of Calpain-2. The functional outcome of GAS2 is highly dependent on the specific substrates of Calpain-2 and cellular environment, particularly within tumor cells. Despite garnering increasing attention and a growing body of related research, a systematic review of GAS2 remains absent. This review aims to elucidate the structural and functional aspects of GAS2, with a particular emphasis on its implications in cancer. By comprehensively detailing its role and research progress in malignancies, this review endeavors to furnish novel insights for enhancing the therapeutic strategies against diseases, particularly cancers.

Oral squamous cell carcinoma (OSCC) affects a substantial proportion of the Asian population and is influenced by various genetic risk factors. The RAR-related orphan receptor beta (RORB), a regulator of the circadian rhythm, has been implicated in certain neoplasms. Accordingly, this study investigated the association between RORB single-nucleotide polymorphisms and clinical manifestations of OSCC. A total of 1174 male patients without OSCC and 1254 male patients with OSCC were included in the study. Three RORB single-nucleotide polymorphism loci-rs3750420 (T/C), rs10781247 (A/G), and rs17611535 (C/T)-were genotyped using TaqMan allelic discrimination assays. RORB single-nucleotide polymorphism rs10781247 variants were significantly associated with moderate to poor cellular differentiation in patients with OSCC (p = 0.042). Additionally, among betel quid chewers with OSCC, rs10781247 variants were significantly associated with moderate to poor cell differentiation (p = 0.036). The rs3750420 variants were significantly associated with larger tumor size in individuals with buccal mucosa cancer (p = 0.036). An analysis of Cancer Genome Atlas data revealed that RORB mRNA levels were significantly higher in patients with head and neck squamous cell carcinoma compared with controls (p = 0.0002). Moreover, RORB mRNA levels were significantly higher in stage IV tumors than in stage III tumors (p = 0.0252). In conclusion, RORB single-nucleotide polymorphisms rs3750420 and rs10781247 are associated with adverse clinical characteristics in OSCC.

Introduction: Most patients with non-small cell lung cancer (NSCLC) have metastases at initial diagnosis. However, the comprehensive molecular characteristics and factors associated with its metastases are still needed. Methods: Tumor sequencing of 556 cancer-related genes was performed on 114 Chinese NSCLC patients. A distinct genomic profile was identified in metastatic patients compared to those without metastases. Kaplan-Meier method was used to analyze the associations between clinical outcomes, clinical characteristics, and mutated genes. The Fisher test and Lasso logistic regression analysis were employed to identify factors related to metastasis and to develop prediction models. Results: Male, squamous cell lung carcinoma, and smokers showed strikingly higher TMB levels in all NSCLCs. The metastatic group had a significantly higher proportion of patients aged ≥ 70 years and in stage III-IV. TP53 was the most frequent mutation in both groups, and EGFR tended to be higher in the metastatic group. The copy number variation events occurred more frequently in the metastatic group. Additionally, predictive models for metastasis (AUC = 0.828), pleural metastasis (AUC = 0.582), and multisite metastasis (AUC = 0.559) were established. Females, and EGFR +, ASXL2-, and STK11- cases had better overall survival (OS). Lung adenocarcinoma, and KMT2D- and STK11- cases had better progression-free survival (PFS). NSCLC metastasis was associated with poor OS and poor PFS. Conclusions: Our study provided a comprehensive analysis of genomic alterations in metastatic NSCLCs, identified novel prognostic biomarkers, and provided three predictive models for metastasis, which may have potential implications for personalized treatment strategies.

Purpose: The thioredoxin (Trx) system is integral to redox regulation and participates in several physiological processes, including tumor growth, immune response, and stem cell differentiation. We have performed a comprehensive and holistic analysis of the Trx system in tumor immunity in this study. Methods: A study using the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases was conducted to determine the expression and distribution of Trx system proteins. To explore and validate the correlation between Trx system expression levels and tumor progression, GTEx and TCGA datasets were used. Western blotting was used to measure Trx system expression in lung cancer cell lines, while MTT assays were used to measure cell proliferation. The Kaplan-Meier plotter database was used to explore the association between the Trx system and survival outcome of patients in pan-cancer. GO and KEGG enrichment analyses of the Trx system were performed. Next, we analyzed how the Trx system related to immune activation. Using TIDE and TISMO databases, we predicted immunotherapy responses. Results: An abnormal expression of the Trx system is observed in cancer cells. Interference with the Trx system with siRNA or inhibitors significantly inhibits tumor cell growth, suggesting the Trx system is crucial to tumor growth. Through a broad cohort of different cancer types, we explored the prominent role of genes in the Trx system. The Trx system showed a relatively consistent aberrant expression in pan-cancer, correlated closely with clinical prognosis. Interestingly, the Trx system was highly correlated with the clinical prognosis in pan-cancer, as well as immunity and metabolism. The abnormal expression of the thioredoxin system was positively correlated with the expression of genes associated with immune infiltration and with a decrease in survival. The Trx system was also associated with immune response to immunotherapy. Conclusion: The Trx system is a good predictor of both survival and the efficacy of immunotherapy, as well as clinical prognosis.

Lung cancer is one of the most harmful cancers in the world, endangering the lives and health of many people. Although there are various methods to treat lung cancer at present, but lung cancer is asymptomatic in the early stages and has a high recurrence rate after late treatment which make it difficult to cure with conventional treatments. Drug combinations for the treatment of lung cancer have been used in many clinical studies. In this study, we constructed a recurrence model of Non-Small Cell Lung Cancer (NSCLC) lung cancer and used a combination of Ginsenoside H dripping pills (GH) and vinorelbine (NVB) to treat the recurrence of lung cancer. The results showed that the inhibition rate of the combined treatment of GH and NVB is 74.81% which is significantly higher than the therapeutic effect of separate use. We also used GC-TOF/MS-based metabolomics to identify differentially abundant metabolites in relapse models and explore biomarker trends. We found that there are 12 metabolite differences in the abundance of metabolites between the treatment groups (GH group, NVB group and GH-NVB group) and the model group, such as glucose 6-phosphate, palmitoleic acid, linoleic acid, guanine, allantoic acid. The differences in these metabolites involve glucose and lipid metabolism, amino acid metabolism, and purine metabolism. We further analyzed the changes in the content of these metabolites and found that the combined use of GH and NVB can regulate purine metabolism, folate synthesis, and thiamine metabolism, ultimately reducing the abnormal increase in alkaline phosphatase (AP). This study provides a method for the treatment of lung cancer and some biomarkers for the detection of lung cancer.

Background: The increasing prevalence of cancer and bacterial resistance necessitates more effective anti-cancer and anti-bacterial treatments. This study explores the potential of medicinal plants, specifically Calotropis procera (C. procera) and Rhazya stricta (R. stricta), in addressing this need, aiming to uncover new therapeutic interventions. Methods: Various extraction methods for the leaves of C. procera and R. stricta were employed to investigate the anti-bacterial and anti-cancer properties of these herbs. For anti-bacterial testing, extracts were prepared using water, chloroform, and ethyl acetate, and their activity against methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) and Escherichia coli (E. coli) was assessed. The anti-cancer potential was evaluated through MTT cytotoxicity assays on various cancer cell lines and further testing using high-content imaging (HCI)-Apoptosis Assay and the ApoTox-GloTM Triplex Assay. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the secondary metabolites of C. procera, and computational predictions were performed to assess the activity of these metabolites. Results: The leaf extracts of both C. procera and R. stricta demonstrated antibacterial activity against S. aureus and E. coli. The C. procera ethyl acetate extract exhibited potent anti-cancer effects on several cancer cell lines. The research also revealed a dose-dependent induction of apoptosis and a decline in cell viability. Computational predictions suggested the identified metabolites were active as nuclear receptor ligands and enzyme inhibitors, with good oral bioavailability. Most metabolites were found to be immunologic and cytotoxic, except for proceragenin and calotropone, which were determined to be non-cardiotoxic. Conclusion: The study's findings demonstrate the remarkable cytotoxic and antibacterial effects of C. procera extracts prepared using ethyl acetate. These results pave the way for further in vitro studies to explore the full potential of these extracts and highlight the presence of chemically active metabolites in C. procera, which hold promise as lead molecules for the development of novel therapies targeting bacterial infections and cancer while minimizing potential side effects.

Objective: Cervical cancer (CC) is one of the most common female malignancies globally. The current study aimed to identify novel hub genes associated with traditional Chinese herbs and investigate their underlying mechanisms using bioinformatics analysis combined with experimental verification. Methods: Expression profiling of 22 samples was obtained from the GEO database. Differential expression analysis was performed using the limma package in R. The Chinese herbal formulas related to the treatment of cervical cancer were searched in the TCMIP database using the keyword "cervical cancer". disease targets associated with cervical cancer were retrieved based on six databases, including the DisGeNet, Genecards, CTD, OMIM, GEO, and TTD databases. The database STRING and Cytoscape were utilized to determine candidate hub genes. The hub genes were further investigated using UALCAN, Kaplan‒Meier-plotter databases, Human Protein Atlas, and the AutoDock Vina software. The results of network pharmacology analysis were verified by in vitro experiments. Results: By intersecting the disease targets with the drug targets, we obtained 49 possible therapeutic targets for cervical cancer. Afterward, we analyzed 49 therapeutic targets using the STRING database and the cytoHubba plugin and eventually obtained six hub genes, MYC, HIF1A, TP53, STAT3, CCND1, and AKT1. The final hub genes were indicated to have significant prognostic relevance in cervical cancer. In addition, the six hub genes were molecularly docked with traditional Chinese medicine for cancer, including quercetin, licochalcone a, nobiletin, naringin, and kaempferol. The results also showed that traditional Chinese medicine could decrease the mRNA and protein expressions, suggesting that quercetin, licochalcone a, nobiletin, naringin, and kaempferol can treat CC by inducing cell apoptosis. Conclusions: We identify six genes that can be therapeutic targets for cervical cancer, confirm that quercetin, licochalcone a, nobiletin, naringin, and kaempferol exert therapeutic effects on cervical cancer by regulating apoptosis pathways through in vitro experiments, and provide insights into the molecular mechanisms of the impact of traditional Chinese medicine in cancer treatment.