BackgroundTo construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo.MethodsThe Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis.ResultsThe positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (P < 0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors.ConclusionThe Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily that induces apoptosis in a broad range of human cancer cell lines while sparing most normal cell types. However, many tumors remain resistant to treatment with TRAIL. In this study, we investigated the synergistic effects of low-dose irinotecan (CPT-11) and TRAIL on TRAIL‑resistant HT-29 colon carcinoma cells and explored potential mechanisms of apoptosis. Cell viability was analyzed by sulforhodamine B (SRB) assay and apoptosis was evaluated by flow cytometry and DNA ladder assay. The mRNA expression of TRAIL receptors death receptor 4 (DR4) and DR5 were determined by reverse transcription polymerase chain reaction (RT-PCR). The changes of Bax and caspase-9 in protein levels were also detected by western blotting. Tumor growth curves were depicted and tumor inhibitive rates were calculated. Our results showed that the antitumor effect of TRAIL could be enhanced significantly by low-dose CPT-11 on TRAIL-resistant HT-29 cells both in vitro and in vivo. The synergistic apoptotic effect of CPT-11 and TRAIL was proposed to be mediated by upregulating DR5 mRNA expression and increasing expression of Bax and caspase-9 proteins. The data suggest that the combination of TRAIL with low-dose CPT-11 could be an effective therapeutic approach for HT-29 colon carcinoma.

Background: A large number of studies have been published to investigate the association between the null genotype of glutathione S-transferase T1 (GSTT1) with gastric cancer. However, the results were inconsistent and conflicting. The aim of this study was to estimate the relationship between this polymorphism in the GSTT1 gene and gastric cancer risk in Asian populations by meta-analysis. Materials and Methods: A literature search was performed in PubMed, Embase, Chinese Biomedical database (CBM), Weipu database, Wanfang database, and China National Knowledge Infrastructure database (CNKI). Statistical analysis was conducted by using Review Manager 5.3. Results: Thirty-nine studies with a total of 7,737 gastric cancer cases and 10,823 controls were included in this meta-analysis. The meta-analysis of total studies showed that the null genotype in GSTT1 was associated with increased risk of gastric cancer in Asians (OR=1.19, 95% CI=1.08-1.31, p=0.0002). Subgroup analysis showed a significant relationship between GSTT1 null genotype and gastric cancer in East-Asians, as well as in subgroup analysis of hospital-based design. On subgroup analysis by smoking status, alcohol status, Helicobacter pylori infection status, and histology type, no significant association of this polymorphism with susceptibility to gastric cancer was found. Conclusions: In conclusion, the results showed that the null genotype of GSTT1 is significantly associated with an increased risk in gastric cancer in Asian populations. (Acar et al., 2006;Sreeja et al., 2008;Liu et al., 2010). Polymorphisms in this gene affect the enzymatic activities and the ability to metabolize carcinogenic compounds (Nebert et al., 1999). The most common variant of GSTT1 gene is homozygous deletion (null genotype), which has been reported to be associated with gastric cancer (Hayes and Strange, 2000). However, the sparseness of data or disagreements among the reported investigations results in the available evidence weakly. To assess the effect of GSTT1 null genotype on gastric cancer risk in Asian population more precisely, we conducted most of the related studies and performed this meta-analysis of published data investigating whether the null genotype of GSTT1 gene was associated with the risk of gastric cancer. Keywords Materials and Methods Publication searchA literature search of PubMed, Embase, Chinese Biomedical database (CBM), Weipu database, Wanfang 1142database and Chinese National Knowledge Infrastructure (CNKI) was conducted using combinations of the following keywords: "gastric cancer or gastric carcinoma or gastric neoplasm" and "polymorphism or variant or mutation" and "GSTT1 or glutathione S-transferase T1". The language was limited to Chinese and English. All studies that evaluate the relationship between polymorphisms in GSTT1 gene and gastric cancer risk were retrieved. Studies included in the meta-analysis had to meet all of the following criteria: (1) evaluation of the polymorphisms in GSTT1 gene and gastric cancer risk, (2) use of ...