ABSTRACT
OBJECTIVE: To compare the clinical efficacy of Jie-du granule preparation versus best supportive treatment in patients with advanced hepatocellular carcinoma. METHODS: A retrospective cohort study was carried out in patients with advanced liver cancer. Patients were divided into Jie-du granule treatment (JD) and best supportive treatment (BST) groups. The main outcomes included median overall survival time. RESULTS: A total of 177 patients with Barcelona Clinic Liver Cancer stage C receiving JD granule treatment or BST were enrolled between January 2012 and December 2014. The overall median survival time was 6.2 months (95% confidence interval [CI] 4.546-7.854) in the JD group versus 4 months (95% CI 3.471-4.529) in the BST group. Significant independent risk factors were alpha-fetoprotein (P = 0.048), Child-Pugh class (P = 0.005), vascular invasion (P = 0.003), and extrahepatic metastasis (P = 0.0018). For patients with two or fewer of these independent risk factors, the overall median survival of those treated with JD was significantly longer than that of patients receiving BST (P < 0.05). CONCLUSION: Jie-du granule preparation may prolong survival of patients with advanced HCC.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Drugs, Chinese Herbal/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Aged , Carcinoma, Hepatocellular/mortality , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Humans , Liver Neoplasms/mortality , Male , Medicine, Chinese Traditional , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Treatment Outcome , Tumor BurdenABSTRACT
Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca(2+) current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca(2+) current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.
Subject(s)
Brain Neoplasms/secondary , Carcinoma/genetics , Carcinoma/pathology , NM23 Nucleoside Diphosphate Kinases/genetics , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Adult , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Berberine/pharmacology , Berberine/therapeutic use , Brain Neoplasms/prevention & control , Carcinoma/drug therapy , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Mice, Nude , Middle Aged , Nasopharyngeal Neoplasms/drug therapy , Neoplasm Invasiveness , Oligonucleotide Array Sequence Analysis , Tumor Cells, CulturedABSTRACT
OBJECTIVES: To search for a new clinical application of melittin (Mel): treating hepatocellular carcinoma with Mel gene. METHODS: Recombinant adenoviruses carrying the Mel gene and alpha-fetoprotein (AFP) promoter (Ad-rAFP-Mel) were constructed through a bacterial homologous recombinant system. The efficiency of adenovirus-mediated gene transfer and the inhibitory effect of Ad-rAFP-Mel on the proliferation of hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-Mel and the antitumor effect of Ad-rAFP-Mel on transplanted tumor in nude mice were detected in vivo. RESULTS: The Mel mRNA was transcribed in BEL-7402 hepatocellular carcinoma cells transducted by Ad-rAFP-Mel. The efficiency of adenovirus-mediated gene transferred to BEL-7402 cells was 100% when the multiplicity of infection of Ad-rAFP-Mel was 10 in vitro, and was also high in vivo. The inhibitive rates of Ad-rAFP-Mel and Ad-rAFP for BEL7402 cells were 66.2 +/- 2.7% and 2.9 +/- 2.3% (t=30.83, P=6.6 x 10(-6)) by MTT assay. The inhibitive rates of Ad-CMV-Mel for BEL7402, SMMC7721 and L02 cells were 58.9 +/- 9.6%, 65.9 +/- 3.8% and 31.7 +/- 1.2%, respectively, and of Ad-rAFP-Mel were 66.2 +/- 2.7%, 16.1 +/- 6.6% and 7.5 +/- 3.3%, respectively (t=1.27, P=0.27; t=11.31, P=3.5 x 10(-4); and t=12.12, P=2.7 x 10(-4) versus the Ad-CMV-Mel group in the same cells). The tumorigenicity rates of hepatocarcinoma cells transfected by Ad-rAFP-Mel were decreased. A significant antineoplastic effect was detected on transplanted tumor in nude mice by intratumoral injection of Ad-rAFP-Mel. CONCLUSIONS: Ad-rAFP-Mel can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo. This suggests that animal toxin gene can be used as an antitumor gene.
