Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis.

PURPOSE: To evaluate and compare the efficiency and safety of raltitrexed- or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). METHODS: We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. RESULTS: The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatment-related death occurred in either group. CONCLUSION: TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway.

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.