Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic.
Gastric cancer is one of the leading causes of tumor-related deaths in China. The tumor, node, metastasis (TNM) classification system is useful for predicting clinical prognosis of patients with gastric cancer. However, determining the presence of lymph node involvement in the early stages of gastric cancer is difficult without biopsy. Therefore, it is necessary to identify novel serum biomarkers for TNM cancer staging and prognostic follow-up. In this study, we have reported fibrinopeptide-A (FPA) with alanine truncation at the N-terminal as a novel biomarker to differentiate gastric cancer with and without lymph node metastases. We analyzed 369 individual serum samples including gastric cancer patients without lymph node metastases (n 5 33), gastric cancer patients with lymph node metastases (n 5 157; confirmed by pathology), and age-and sex-matched healthy individuals (n 5 179). The data showed that 85.4% of patients with lymph node metastases were positive for FPA with alanine truncation at the N-terminal (degAla-FPA, 1,465.63 Da), as determined by tandem mass spectrometry (MS). Using degAla-FPA as the biomarker, the sensitivity was 85.4% for gastric cancer patients with lymph node metastases, and the specificity was 100% for gastric cancer patients without lymph node metastases. The high sensitivity and specificity achieved with serum degAla-FPA levels indicated that MS technology could facilitate the discovery of a novel and quantitative prognostic biomarker for gastric cancer with lymph node involvement. Anat Rec, 296:590-594,
A technology of swelling and suspension copolymerization was conducted to graft styrene onto linear lowdensity polyethylene (LLDPE). The graft mechanism of styrene with LLDPE had been described by 1 H NMR and IR. The mean particle diameter and size distribution of the products with different proportions of LLDPE to styrene monomer were calculated. The morphology and thermal behavior of copolymers were characterized by scanning electron microscopy and differential scanning calorimetry. The glass transition temperature of copolymers increased with the addition of LLDPE, which proved the existence of the polyethylene-g-polystyrene copolymer. The grafting efficiency and granulation rate of suspension copolymerization were investigated. It was found that the grafting efficiency increased and the granulation rate decreased with the addition of LLDPE.
Background
Programmed death receptor-1 (PD-1) immune checkpoint inhibitors (ICIs) have produced encouraging results in hepatocellular carcinoma (HCC) patients. Cytokine-induced killer (CIK) cells treatment can specifically identify tumor-associated antigens and has encouraging preliminary efficacy for HCC. This study reported two cases of HCC patients achieved complete response (CR) by anti-PD-1 antibody therapy post-progression on bi-specific antibody conjugated CIK immunotherapy.
Case Presentation
Case one, a 75-year-old male, was diagnosed with the intrahepatic cholangiocarcinoma (ICC) in October 2017. After interventional, CIK, ablation and other comprehensive therapy, ICC was gradually cured. When new occurrence of HCC, he was treated with anti-PD-1 antibody therapy and achieved CR. Case two, a 65-year-old female, was diagnosed with HCC in July 2016. After progression on several ablation treatments, she received 8 cycles of CIK treatment and achieved stable disease (SD). After disease progressed on CIK treatment, she received 4 cycles of anti-PD-1 antibody therapy, finally achieved CR.
Conclusion
Anti-PD-1 antibody therapy after prior progression on bi-specific antibody conjugated CIK immunotherapy may be efficacy and safety for HCC patients.
ObjectiveThis systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC).BackgroundSeveral studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking.MethodsStudies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0.ResultsThirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26–0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31–0.65; nICT: 0.29, 95% CI: 0.26–0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1–2 and 3–4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56–0.84) and 0.16 (95% CI: 0.09–0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3–4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17–0.77; nICT: 0.14, 95% CI: 0.07–0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15–0.53; cisplatin: 0.04, 95% CI: 0.01–0.09; p<0.01).ConclusionNeoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.
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