Efficacy of sorafenib combined with transcatheter hepatic arterial chemoembolization in treating intermediate-advanced hepatocellular carcinoma.

PURPOSE: To explore the efficacy and safety of sorafenib combined with transcatheter hepatic arterial chemoembolization (TACE) in the treatment of intermediate-advanced hepatocellular carcinoma (HCC). METHODS: A total of 132 intermediate-advanced HCC patients were divided into two groups, namely, control group (n=66, TACE) and Sorafenib group (n=66, TACE combined with sorafenib). Then, the clinical efficacy and incidence rate of adverse reactions were compared s. Besides, the levels of tumor markers and liver function indicators were detected before and after treatment. Additionally, the survival of patients was followed up and recorded. RESULTS: The overall response rate (ORR) and clinical benefit rate (CBR) were significantly higher in Sorafenib group than those in control group. Both Sorafenib group and control group exhibited significantly lowered levels of serum AFP, CEA, CA125 and CA19-9 after treatment compared with those before treatment. In addition, such levels were prominently lower in Sorafenib group than those in control group after treatment. Compared with those before treatment, the levels of total bilirubin (TBil) and alanine aminotransferase (ALT), liver function indexes, significantly rose, while the albumin (Alb) level had no obvious changes in the two groups after treatment. Besides, the liver function indexes displayed no statistically significant differences between the two groups after treatment. Based on the results of follow-up, the median overall survival (OS) and 3-year OS were 16.83 months and 25.8% in Sorafenib group and 12.48 months and 15.2% in control group, respectively. CONCLUSION: Sorafenib combined with TACE achieves better clinical efficacy in the treatment of intermediate-advanced HCC in contrast with TACE alone, which is able to significantly reduce the levels of serum tumor markers and prolong the survival of patients, and results in tolerable adverse reactions.

Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese.

BACKGROUND: High-density lipoprotein (HDL) is a major plasma lipoprotein directly associated with cholesterol metabolism. The ATP binding cassette transporter 1 gene (ABCA1) is one of the major genes modulating plasma levels of HDL-cholesterol (HDL-C). Rare alleles of ABCA1 associated with extreme HDL-C concentrations have not been previously investigated in the Chinese. METHODS: Blood samples were collected from 470 subjects whose HDL-C concentrations were within the top 5% of the distribution, 335 subjects in the lowest 5%, and 220 within the range 5%-95%. First, we sequenced all exons of the ABCA1 gene from 50 subjects from the group with extremely high HDL-C, and 50 from the group with extremely low HDL-C concentrations. Next, in the remaining subjects, we genotyped the non-synonymous variants identified exclusively with either extreme group. RESULTS: Four novel non-synonymous alleles were identified; all were rare. Alleles c.3029C>T (p.Ala1010Val) and c.5399A>G (p.Asn1800Ser) were found exclusively in the low group, c.2031C>A (p.Asp677Glu) and c.2660G>T (p.Cys887Phe) exclusively in the high group. CONCLUSIONS: Our results show that some rare alleles of ABCA1 are associated with marked phenotypes, supporting the "rare-variant common-disease" hypothesis. Certain alleles also provide tools for identifying individuals at high risk of dyslipidaemia, allowing for early therapeutic intervention.

[Killing effect of double suicide genes mediated by retroviral vector on k562 cells].

The aim of study was to investigate the killing effect of double suicide gene system mediated by retroviral vector on K562 cells in vivo and ex vivo. CDglyTK gene was transfected into PA317 cells by using lipofectamine. K562 cells were infected with viral supernatant. K562/CDglyTK cells were treated with 5-fluorocytosine (5-FC) and/or ganciclovir (GCV). Mice were randomly divided into three groups: tumor formation, tumor inhibition and tumor therapy. Each mouse was implanted with K562/CDglyTK cells or K562 cells. The results indicated that the killing effect of 5-FC in combination with GCV on K562/CDglyTK was more significant than using 5-FC or GCV alone. In vivo study showed that after being injected subcutaneously with K562 cells and K562/CDglyTK cells, there was not obvious difference in tumor formation rate of mice, 5-FC + GCV could suppress tumor formation of the K562/CDglyTK cells. After being treated with 5-FC and GCV, the median tumor volume of mice implanted with K562/CDglyTK cells decreased obviously, compared with the control group. Their median survival was significantly prolonged. It is concluded that double suicide genes are more effective for killing effect on K562 cells in vivo and in ex vivo. It may be applicable to clinical gene therapy.