Trimethyl chitosan-cysteine-based nanoparticles as an effective delivery system for portulacerebroside A in the management of hepatocellular carcinoma cells in vitro and in vivo.

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan-cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.

A multicenter retrospective analysis: Factors influencing hepatic adverse events induced by immunotherapy in advanced liver cancer.

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.

SP1/RNASEH2A accelerates the development of hepatocellular carcinoma by regulating EMT.

Background: The expression level of Ribonuclease H2, subunit A (RNASEH2A) in hepatocellular carcinoma (HCC) has been reported, but the function of RNASEH2A on HCC cells development and the related molecular mechanisms remain unclear. Herein, we intend to explore the upstream regulator of RNASEH2A and its role in the HCC progression. Methods: GEPIA website was employed to determine the level of RNASEH2A in HCC tissues and get a survival analysis. After reducing RNASEH2A expression by RNA interference, cell counting kit-8, colony formation, Western blot, Transwell and wound healing assays were performed to estimate the malignant properties of HCC cells. The transcriptional factor of RNASEH2A was predicted by UCSC and JASPAR database and confirmed by dual luciferase assay and Ch-IP assay. The expression level of EMT pathway related molecules was determined by western blotting. Results: An increased expression of RNASEH2A was presented in HCC and predicted worse prognosis of HCC patients. Functionally, the results demonstrated that depletion of RNASEH2A suppressed HCC cell proliferation, cell cycle, migration and invasion. Moreover, we illustrated that SP1 targeted to the promoter of RNASEH2A and modulated its expression in HCC cell lines. RNASEH2A knockdown counteracted the function of SP1 overexpression in modulating HCC cell growth, cell cycle, and mobility. Then, our data showed that the SP1/RNASEH2A axis affected the malignant behaviors of HCC cells by regulating EMT process. Conclusions: In summary, these results demonstrated that RNASEH2A promoted HCC cells development through regulating EMT process and was transcriptionally modulated by SP1.

TNNT1, a prognostic indicator in colon adenocarcinoma, regulates cell behaviors and mediates EMT process.

Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial-mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson's analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments.

[Analysis of prognostic factors and treatment of pulmonary metastasis from colorectal cancer].

OBJECTIVE: To investigate effect of the treatments and prognostic factors of patients with pulmonary metastasis from colorectal cancer. METHODS: Clinical data of 79 patients who suffered from lung metastatic diseases from colorectal cancer in 1990 - 2010 were retrospectively analyzed. The number of patients who had received lung operation was 22, and non-operated group contained 57 patients. Compared the prognosis of operated group and non-operated group and analyzed the prognostic factors. RESULTS: The median survival time after the pulmonary resections was 34.5 months; the overall survival of 1-, 3- and 5-year survival rates were 90.9%, 45.4% and 4.5%, and the overall of 1-, 3-, and 5-year survival rate in non-operated group were 59.6%, 14.0% and 0. The surgery (RR = 4.805, 95% CI: 1.864 - 12.384, P = 0.001) and the number of metastasis (RR = 2.177, 95% CI: 1.431 - 3.314, P = 0.010) were the factors that could influence the patients prognosis. CONCLUSION: The surgery for pulmonary metastases from colorectal cancer is effective.

[Therapeutic strategy and prognostic factors in colorectal cancer patients with pulmonary metastasis].

Patients with pulmonary metastasis from colorectal cancer have been considered to be associated with poor prognosis. It is a problem to improve survival for patients who suffer pulmonary metastasis from colorectal cancer by analyzing the prognosis of patients who underwent pulmonary surgery or not and then choose the right treatment regimen. The identification of prognostic factors is particularly important in colorectal cancer patients with pulmonary metastasis.