Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta-analysis.

Lentinan is a common biological response modifier. This study was sought to evaluate the efficacy of adjuvant lentinan combined with chemotherapy for advanced cancer. A meta-analysis of published prospective controlled trials investigating the effects of lentinan for kinds of advanced cancer was performed. Sensitivity analysis, inverted funnel plots, and trial sequence analysis were conducted to explore the reliability and stability of results. Seventeen clinical studies were identified containing 1423 patients. Twelve trials included gastrointestinal cancer (GIC), three trials included lung cancer (LC), and two trials included the two cancers. There was a increase in survival rate in 1 year (risk ratios [RR], 1.46, P = 0.001) and overall response rate including both complete and partial response (RR, 1.28, P = 0.005). There was also a reduction in progressive disease (RR, 0.57, P = 0.0005), nonsevere adverse events (RR, 0.88, P = 0.004), and severe adverse events (RR, 0.73, P = 0.007). Similar results were shown in the two subgroups of GIC and LC. Limited trials reported the data of median overall survival and time to treatment failure, and the data were insufficient for quantitative analysis, and no significant difference were found in 2-year survival rate. Adjuvant lentinan used with chemotherapy achieved improvements in 1-year survival rate, response rate, and adverse events in advanced cancer. The effect seemed to be similar irrespective of cancer type. However, its sustained efficacy on survival was still unclear.

HBV promotes the proliferation of hepatic stellate cells via the PDGF-B/PDGFR-ß signaling pathway in vitro.

The activation of hepatic stellate cells (HSCs) is closely associated with liver fibrosis in chronic hepatitis B virus (HBV) infection. However, the molecular mechanisms leading to HSC activation remain unclear. It has been reported that the platelet-derived growth factor-B (PDGF-B)/PDGF receptor-ß (PDGFR-ß) signaling pathway is involved in this process. Thus, we investigated whether HBV and its protein contribute to HSC proliferation by the PDGF-B/PDGFR-ß signaling pathway. HBV particles were purified from the supernatant of HepG2.2.15 cells by ultracentrifugation and the cell lines carrying HBV preS, e, c or x genes were obtained. After incubation with HBV particles or co-cultured with the cell lines expressed in the viral protein, the proliferation of LX-2 cells, an HSC cell line, were detected by flow cyto-metry and real-time PCR and the expression of molecules related to the PDGF-B/PDGFR-ß signaling pathway were further measured. Our results indicated that HBV particles, c and x proteins promoted LX-2 proliferation and increased the mRNA levels of PDGF-B, PDGFR-ß, collagen-I and α-smooth muscle actin (α-SMA), as well as the phosphorylation of PDGFR-ß; however, the expression protein levels of PDGF-B and PDGFR-ß remained unchanged. In conclusion, HBV particles and HBV c and x proteins promote HSC proliferation and fibrogenesis in vitro and the PDGF-B/PDGFR-ß signaling pathway is important in this process.

Hepatitis B virus directly promotes collagen I expression of LX-2 cells without infection in vitro.

AIM: To investigate direct effects of hepatitis B virus (HBV) on collagen type I in vitro. METHODS: Collagen type I were measured after LX-2 cell cultured with purified or serum HBV for 12, 24 and 48 h. Furthermore, evidence of HBV infection to LX-2 were detected, and different inhibitors were used to identify pathways regulating collagen I expression. RESULTS: The 3 × 10(5) IU/mL purified/serum HBV increased collagen type I mRNA expression by 2.2-/3.2- and 1.3-/1.5-fold at 24 and 48 h, respectively. Collagen type I protein in the supernatant of purified/serum HBV group also increased compared to the control group (408.0 ± 8.0/384.4 ± 6.8 vs 262.7 ± 15.7 ng/mL, P < 0.05). However, the 3 × 10(7) IU/mL purified/serum HBV increased collagen type I expression similar to that of 3 × 10(5) IU/mL, while 3 × 10(3) IU/mL group showed no effect. Human HBV immunoglobulin alleviated HBV-induced collagen I expression, but no evidence of HBV infection was found. Neutralization of transforming growth factor beta, tumor necrosis factor alpha, platelet-derived growth factor, extracellular signal-regulated kinase and TGF-ß receptor had no obvious inhibitory effects; only inhibition of p38 mitogen-activated protein kinase decreased collagen type I mRNA expression by 0.5-/0.4- and 0.4-/0.3-fold at 24 and 48 h, respectively. It reduced collagen type I protein in the purified/serum HBV group for 48 h (252.1 ± 14.1/251.7 ± 18.8 vs 403.9 ± 4.9/385.0 ± 4.2 ng/mL, P < 0.05). CONCLUSION: HBV directly promotes collagen type I expression of LX-2 cells without infection in vitro.