ABSTRACT
Active polysaccharides have unique advantages in inhibiting cancer cell proliferation, invasion and metastasis and inducing apoptosis. Yulangsan polysaccharide (YLSPS) is derived from the root of Millettia pulchra var. laxior (Dunn) Z. Wei. Previous studies revealed that YLSPS exhibits bioactivities such as antibacterial, antidepressive, antitumor, hepatoprotective and immunomodulating activities. However, the anticancer effects of YLSPS on lung cancer have not yet been studied, and its mechanism of action remains unclear. The present study investigated the anti-migration/invasion effects of YLSPS and possible mechanisms in lung cancer cells (A549 and Lewis) in vitro and in vivo. The data suggested that YLSPS reversed epithelial-mesenchymal transition (EMT) and inhibited the invasion and migration of lung cancer cells by inhibiting the TGF-ß1-induced ERK signaling pathway. Furthermore, YLSPS reduced the levels of proteins associated with EMT, including vimentin, but increased those of E-cadherin, as determined by Western blotting. In vivo, YLSPS significantly inhibited the growth of xenograft tumors, and decreased the levels of TGF-ß1 and protein markers associated with EMT. Importantly, YLSPS had fewer toxic side effects than cisplatin. Overall, YLSPS significantly delayed non-small cell lung cancer (NSCLC) progression by modulating EMT and TGF-ß1/ERK signaling pathway. The present findings suggest that YLSPS may be a potential adjuvant therapy and drug for improving the tumor microenvironment of lung cancer.
ABSTRACT
AIM: To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM). METHODS: This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups. RESULTS: Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five-year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group. CONCLUSION: Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths.
