An increasing amount of evidence indicates that the inhibition of β adrenergic signaling can result in the inhibition of tumor growth. However, the role of propranolol in liver cancer and the underlying mechanism remain to be elucidated. The present study aimed to investigate the role of propranolol in liver cancer cell lines and provide evidence for further clinical study. Propranolol was added at different concentrations to HepG2 and HepG2.2.15 liver cancer cells and HL-7702 normal human liver cells. The proliferation of the cell lines was monitored by live-cell imaging at a range of time intervals. Immunofluorescence using DAPI and Hoechst 33342/propidium iodide (PI) staining, Annexin V-FITC/PI double-staining flow cytometry, western blotting and reverse transcription-quantitative polymerase chain reaction were used to investigate the effect of propranolol on liver cancer cell apoptosis. The proliferation of HepG2 and HepG2.2.15 cells was inhibited by 40 and 80 µmol/l propranolol. However, the proliferation of HL-7702 cells was not affected by <160 µmol/l propranolol. Propranolol treatment decreased the expression of adrenergic receptor β-2 to a greater extent than adrenergic receptor β-1, and induced apoptosis in the liver cancer cells. The apoptotic rates of HepG2 and HepG2.2.15 cells increased following treatment with propranolol, while the apoptotic rate of HL-7702 cells was not affected. Propranolol promoted poly (ADP-ribose) polymerase cleavage and decreased the expression of full-length caspase-3 in liver cancer cell lines; it induced S-phase arrest in HepG2 and HepG2.2.15 cell lines, while HL-7702 cells were arrested at the G0/G1 phase of the cell cycle. Thus, it was demonstrated that propranolol inhibited proliferation, promoted apoptosis and induced S-phase arrest in HepG2 and HepG2.2.15 cells.
AimThe present study aimed to evaluate the durability of immune response after basic and booster immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver disease (CLD).MethodsPatients with CLD and complete basic or booster immunization with SARS-CoV-2 vaccines were included in this study. Based on the vaccination situation, they were divided into the basic immunity group (Basic) and the booster immunity group (Booster), which were then subdivided into four groups according to the time interval from completion of basic immunization or booster immunization to serological specimen collection. The positive rates and antibody titers of novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD) were analyzed.ResultsA total of 313 patients with CLD were enrolled in this study, including 201 in Basic and 112 in Booster. The positive rates of nCoV NTAb and nCoV S-RBD within 30 days of completing basic immunization were 80.4% and 84.8%, respectively, but decreased rapidly with the extension of vaccination time, and only 29% and 48.4% of patients with CLD remained positive for nCoV NTAb and nCoV S-RBD, respectively, after 120 days of completing basic immunization. Within 30 days of booster immunization, the positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD rapidly increased from 29.0% and 48.4% at the end of basic immunization to 95.2% and 90.5%, and maintained a high level (defined as the positive rate >50%) until 120 days when the positive rates of nCoV NTAb and nCoV S-RBD were still high at 79.5% and 87.2%, respectively. After basic immunization, the time for nCoV NTAb and nCoV S-RBD to turn negative was 120 and 169 days, respectively, and the negative time of nCoV NTAb and nCoV S-RBD was significantly prolonged to 266 days and 329 days, respectively.ConclusionIt is safe and effective for patients with CLD to complete basic and booster immunization with SARS-CoV-2 vaccines. After booster immunization, the immune response of patients with CLD was further improved and the durability of the SARS-CoV-2 antibody was significantly prolonged.
Hepatocellular carcinoma (HCC) has a poor prognosis due to its asymptomatic onset and susceptibility to metastasis. The survival of patients with advanced HCC is 6–12 months. As a first-line medicine for the control of hepatitis B virus, interferon (IFN) is also capable of inhibiting tumor growth and modulating immunity. However, treatment of HCC with lung metastasis using IFN has been rarely reported. The present study reports the case of one patient with HCC having lung metastasis who underwent a one-time treatment with transcatheter arterial chemoembolization (TACE) and was subsequently completely cured by single peginterferon α 2a (PEG-IFNα2a); and has survived up to 108 months. A 53-year-old male patient diagnosed with HBV-related HCC with lung metastasis underwent TACE using floxuridine (FUDR) 500 mg, cisdiamine dichloroplatinum (CDDP) 20 mg, mitomycin 10 mg, and ultrafluid lipiodol 10 ml, together with local thoracic aorta chemotherapy using FUDR 250 mg and CDDP 20 mg. His metastatic lung cancer aggravated. However, after 9 months of treatment with subcutaneous injections of PEG-IFNα 2a once per week, the metastatic lung foci gradually shrunk until disappearance and the HCC lesion stabilized without progression. According to the World Health Organization criteria for the efficacy of solid tumors, this was a case of complete response. Upon follow-up up to 108 months his metastatic lung cancer had disappeared and HCC did not recur. Therefore, IFN intervention may be an appropriate novel adjuvant therapy for patients with HCC with lung metastasis and requires further attention and study.
This article is aim to investigate the safety and immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine booster in patients with chronic liver disease(CLD). A total of 114 patients with CLD who received a SARS-CoV-2 vaccine booster were enrolled in this study. Serum samples were collected from enrolled patients at least 14 days after the booster dose and tested for SARS-CoV-2 neutralizing antibody (novel coronavirus neutralizing antibody, nCoV NTAb) and IgG antibody against SARS-CoV-2 spike binding domain(novel coronavirus spike receptor-binding domain antibody,nCoV S-RBD antibody)levels. The positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD were 87.72% and 91.23%, respectively, after the booster injection of coronavirus disease 2019 (COVID-19) vaccine. The booster injection resulted in the production of nCov NTAb in 66.7% of patients and nCov-SRBD antibody in 71.43% of patients with CLD who failed basic immunization. After basic SARS-CoV-2 immunization, the booster SARS-CoV2 vaccine increased the serum conversion rate and the level of nCov NTAb and nCov-SRBD antibodies in patients with CLD (including patients with cirrhosis). The severity of the liver disease is related to the immune response to COVID-19 vaccine.
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