B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis.

PURPOSE: The essential action of B7 homolog 3 (B7-H3) in different diseases and cancers has been documented. We here focused on its role in breast cancer through the Raf/MEK/ERK axis regarding lung metastasis. METHODS: Expression pattern of B7-H3 was determined in breast cancer tissues and cells with its correlation with prognosis analyzed. Then, through transfection of lentivirus vector expressing B7-H3-shRNA, overexpression vector of B7-H3 (B7-H3-LV), U0126 (small molecule inhibitor of MEK), or PD98059 (small molecule inhibitor of ERK), the in vitro and in vivo effects of B7-H3 in breast cancer cell biological processes, and lung metastasis were analyzed in relation to the Raf/MEK/ERK axis. RESULTS: We discovered elevated B7-H3 in breast cancer and its elevation associated with poor prognosis. B7-H3 promoted the malignant properties of breast cancer cells, accompanied with increased N-cadherin and vimentin and reduced E-cadherin. Additionally, overexpression of B7-H3 accelerated the lung metastasis in breast cancer in vivo. All the above promoting action of B7-H3 was achieved through activation of the Raf/MEK/ERK signaling pathway. CONCLUSION: Taken together, B7-H3 can promote lung metastasis in breast cancer through activation of the Raf/MEK/ERK axis.

Molecular targeted therapy and immunotherapy in advanced hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis based on randomized controlled trials.

OBJECTIVE: The aim of this study was to compare and rank different targeted therapies or immunotherapies for advanced hepatocellular carcinoma based on efficacy. METHODS: A systematic search of the PubMed, EMBASE, and Cochrane Library databases was conducted. All systematic treatment regimens that reported comparisons with sorafenib were included in this analysis. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and other outcome measures included the objective response rate (ORR) and safety analysis according to reported treatment-related adverse events. RESULTS: A total of 29 RCTs involving 13376 patients were included in the analysis, including 10 single-agent therapies and 17 combination therapies. Compared with sorafenib, sintilimab plus IBI305 (HR: 0.57, 95% CI: 0.43-0.75), camrelizumab plus rivoceranib (HR: 0.62, 95% CI: 0.49-0.78), and atezolizumab plus bevacizumab (HR: 0.66, 95% CI: 0.52-0.83) ranked in the top three in terms of OS. CONCLUSIONS: PD-1/PD-L1 inhibitors combined with anti-vascular endothelial growth factor (anti-VEGF)-targeting drugs have shown better therapeutic effects in the systematic treatment of patients with advanced hepatocellular carcinoma, and the combination of targeted and immune therapy modes should be further developed.

Liver resection, radiofrequency ablation, and radiofrequency ablation combined with transcatheter arterial chemoembolization for very-early- and early-stage hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis for comparison of efficacy.

Objective: To compare the efficacy of liver resection (LR), radiofrequency ablation (RFA), and radiofrequency ablation combined with transcatheter arterial chemoembolization (RFA+TACE) in the treatment of very-early- and early-stage hepatocellular carcinoma (HCC). Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) and observational analyses with propensity score-matched cohort analyses (PSMs) comparing any two of the three treatments were included in this study. The primary result was overall survival (OS) and the secondary result was recurrence-free survival (RFS), which were analyzed by calculating the hazard ratio (HR) and 95% confidence intervals (CI). Results: A total of 25 studies (4249 patients), including 10 RCTs and 15 PSM observational studies, met the inclusion criteria. Although there was no significant difference between LR and RFA in terms of one-year OS, though LR showed superior performance for three- and five-year OS (at three years, HR: 0.74, 95% CI: 0.56-0.96; at five years, HR: 0.73, 95% CI: 0.55-0.94). In addition, significantly higher rates of RFS at one-, three- and five-year follow-up were found for LR than for RFA alone (at one year, HR: 0.68, 95% CI: 0.51-0.92; at three years, HR: 0.67, 95% CI: 0.55-0.81; at five years, HR: 0.61, 95% CI: 0.48-0.78). The combination of RFA+TACE was superior to RFA alone based on one-year RFS (HR: 0.57, 95% CI: 0.34-0.96), while there were no significant differences in OS at one, three, and five years, and in RFS at three and five years. Conclusions: For very-early- and early-stage HCC, this systematic review and network meta-analysis showed that the efficacy of LR is superior to that of RFA alone, regardless of whether the evaluation is based on either OS or RFS. The advantages of RFA+TACE compared to RFA alone are limited, and further studies are needed to determine whether combination therapy is necessary, i.e., results in significantly improved outcomes. Systematic Review Registration: The study was registered with http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022299269.

Prediction of outcomes by diffusion kurtosis imaging in patients with large (≥5 cm) hepatocellular carcinoma after liver resection: A retrospective study.

Purpose: To evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR). Materials and methods: From January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant. Results: A total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895. Conclusion: The MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.