Vicenin-2 Treatment Attenuated the Diethylnitrosamine-Induced Liver Carcinoma and Oxidative Stress through Increased Apoptotic Protein Expression in Experimental Rats.

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.

Synergistic role of Caspase-8 and Caspase-3 expressions: Prognostic and predictive biomarkers in colorectal cancer.

BACKGROUND: Expressions of Caspase-8 and Caspase-3 have been identified as important markers in many malignant tumors, but their roles in colorectal cancer (CRC) have not been confirmed. The purpose of this study was to investigate the role of Caspase-8 and Caspase-3 in CRC. METHODS: We enrolled 470 CRC patients in this study. Archival paraffin-embedded CRC tissue samples were used to construct tissue microarray (TMA), expressions of Caspase-8 and Caspase-3 that were stained by immunohistochemistry. Prognostic and predictive role of Caspase-8 and Caspase-3 expressions, alone or united, were evaluated by univariate and multivariate analysis respectively. RESULTS: In comparison with adjacent normal tissues, Caspase-8 and Caspase-3 protein levels were upregulated in CRC tissues significantly, furthermore, high expressions of Caspase-8 and Caspase-3 were correlated with decreased overall survival (OS) (p< 0.05), and also with unfavorable clinicopathologic characteristics. Cox regression analysis showed that high Caspase-8 and Caspase-3 expressions were independent negative markers of OS. CONCLUSION: Caspase-8 and Caspase-3 expressions in tumor tissues are novel candidate prognostic markers for CRC patients. It was the first time to be identified that Caspase-8 and Caspase-3 expressions had synergistic role as efficient prognostic indicators for CRC patients.

S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: a meta-analysis.

AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC). METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values. RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens. CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use.