Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase-9, caspase-3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β-Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase-9, caspase-3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase-9, caspase-3, p53, and p21. The shCCNB1 group had decreased proliferation and S-phase cell proportion and increased apoptosis, senescence, and G0/G1-phase cell proportion. The PFT-α group showed higher expressions of MDM2 and lower expressions of Bax, caspase-9, caspase-3, p53, and p21. The PFT-α group had increased proliferation and S-phase cell proportion and declined apoptosis, senescence, and G0/G1-phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.
Liver resection may be beneficial in intermediate-stage hepatocellular carcinoma (HCC), though the benefit of postoperative anti-hepatitis B virus (HBV) therapy in these patients remains unclear. In this study, we sought to evaluate the efficacy of postoperative anti-HBV for intermediate-stage HCC patients who underwent radical liver resection.According to inclusion and exclusion criteria, this study enrolled 202 HCC patients who underwent liver resection and had a high HBV-DNA load. The patients were divided into 2 groups on the basis of postoperative anti-HBV therapy: group A included patients undergoing postoperative anti-HBV therapy, whereas group B patients did not receive any postoperative anti-HBV therapy. Factors including baseline demographics, tumor characteristics, overall long-term survival, tumor-free survival, and tumor recurrence rate were compared between the 2 groups. Moreover, univariate and multivariate analyses were used to identify risk factors of HCC recurrence.Baseline demographics and tumor characteristics were comparable between the groups. The 1-, 3-, and 5-year overall survival rates in group A were 91.3%, 80.9%, and 66.1%, respectively, values that were significantly increased compared with group B (91.7%, 60.7%, and 52.4%, respectively, P = .019). Group A patients also exhibited enhanced 1-, 3-, and 5-year tumor-free survival compared with group B patients (87.0%, 67.0%, and 62.6%, respectively, in group A; 82.1%, 50.0%, and 42.9% in group B, P = .002). In addition, the tumor recurrence rate in group B was significantly increased compared with group A (P < .01). Univariate and multivariate analyses indicated lack of postoperative anti-HBV therapy [hazard ratio (HR) = 0.882; 95% confidence interval (CI), 0.712–0.938; P = .042] to be a predictor of tumor recurrence.For intermediate-stage [Barcelona Clinic Liver Cancer (BCLC) stage B] HCC with a high HBV-DNA load, postoperative anti-HBV therapy after curative resection should be routine adjuvant therapy.
It is unclear whether hepatic artery infusion chemotherapy (HAIC) or transcatheter arterial chemoembolization (TACE) is more efficient in the combination therapy of hepatocellular carcinoma (HCC). Head-to-head comparisons among HAIC-related therapies are lacking. For this network meta-analysis, PubMed, EMBASE and Cochrane Library databases were searched up to April 1, 2022. Randomized controlled trials (RCTs) were eligible if they evaluated the use or prolongation of TACE or HAIC in patients with advanced HCC and reported or collected survival data. A network meta-analysis was performed to synthesize data and make direct and indirect comparisons between treatments. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to explore the efficacy of various treatment options on overall survival (OS), odds ratios (ORs) with 95% CI were used for overall response rate (ORR), whereas risk ratios (RRs) with 95% CI were used for serious adverse events (SAEs). The analysis of 7 trials including a total of 1,073 patients found that sorafenib with HAIC-oxaliplatin improved survival (HR= 0.33, 95% CI: 0.25-0.44); the ORR was also improved in patients treated with sorafenib plus HAIC-oxaliplatin and sorafenib plus PF-HAIC (OR=22.18, 95% CI: 10. and OR=2.72, respectively). The incidence of liver injury was elevated in patients treated with sorafenib plus TACE (OR=5.93, 95% CI: 2.70-15.41). However, no differences in the incidences of other SAEs were identified among the treatment groups. The present meta-analysis provides preliminary evidence for the comparative safety and efficacy of HAIC and TACE combined with sorafenib, and indicates the dominance of HAIC-oxaliplatin in HCC interventional therapy. However, high-quality RCTs are required to further confirm the efficacy of HAIC-oxaliplatin. The present study has been registered with PROSPERO (registration no. CRD42021288497).
Background: Skeletal muscle depletion and excessive visceral adipose tissue have been shown to be independent risk factors for postoperative complications (PCs) in various diseases. However, their impact on surgical PCs in hepatic alveolar echinococcosis (HAE) is still unknown. Methods:We retrospectively reviewed the clinical data of HAE patients who underwent liver resection at our hospital between January 2008 and December 2018. We segmented skeletal muscle and adipose tissue and measured the area of skeletal muscle tissue and adipose tissue at the level of the third lumbar vertebra by manual tracing from preoperative plain computed tomography (CT) images. Sarcopenia features were selected to construct a formula based on the least absolute shrinkage and selection operator (LASSO) logistic regression model in the primary set. Then, integrating the results of multiple clinicopathologic characteristics, we built a nomogram for predicting major PCs in HAE. The results were validated using bootstrap resampling and clinical data from other HAE centers in western China. Results:The sarcopenia score is based on the personalized levels of the five features from the primary set (n=233). In the multivariate logistic analysis of the primary set, the independent factors for PCs were γ-glutamyl transferase (GGT), and surface area of hepatectomy, which were integrated into the nomogram combined with sarcopenia score. The model had a good prediction capability with a C-index of 0.84 (95% CI, 0.72-0.96). The calibration plot for the probability of PCs showed an optimal agreement between the nomogram predictions and actual observations in the primary and validation sets. Conclusion:Our study showed that sarcopenia score was significantly correlated with PCs in patients with HAE. In addition, we constructed a prognostic nomogram for predicting complications in HAE patients after liver surgery. The nomogram displayed excellent discrimination and calibration. Improving the nutritional status and physical health of patients before surgery might reduce the incidence of postoperative complications for the high-risk patients.
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