Wnt/ß-catenin aids in regulating the proliferation of hepG2 cells mediated by thy-1.

Cancer stem cells have been found to play important roles in carcinoma. Although thy-1 has been identified as a potential stem cell marker of liver cancer, whether the Wnt/ß-catenin signaling pathway plays an important role in regulating hepatocarcinoma proliferation and apoptosis mediated by thy-1 remains unknown. Our results showed that high thy-1 expression caused hepG2 cells transfected with a pReceiver-M29/thy-1 eukaryotic expression vector to exhibit obvious heteromorphism, featuring double or multiple nuclei and weaker apoptosis. A high expression of ß-catenin, as a critical signaling protein of Wnt/ß-catenin, and its downstream transcription factor, cyclinD1, were detected in transfected hepG2 cells. We also used aspirin as an inhibitor of the Wnt signaling pathway in the treatment of hepG2 cells transfected with the pReceiver-M29/thy-1 expression vector to make detailed observations of apoptosis in hepG2 cells as well as the differential expression of ß-catenin, cyclinD1, and thy-1. An increasing apoptosis rate was detected in the hepG2 cells and downregulated expression of the three proteins was detected. Hence, we suggest that thy-1 upregulation promotes the proliferation and inhibits apoptosis of hepG2 cells, and that these processes are regulated by the Wnt/ß- catenin signaling pathway.

Pancreatic cancer cells expressing hypoxia-inducible factor-1α tend to be adjacent to intratumoral blood vessels.

We investigated whether cells expressing hypoxia-inducible factor-1α (HIF-1α) are specially related to blood vessels in human pancreatic tumors. HIF-1α and blood vessels were stained in 7 pancreatic ductal adenocarcinomas (PDAC) and 3 nonmalignant tumors. HIF-1α(+) cells accounted for 37 ± 5% of the total PDAC cells and increased to 52 ± 4% in perivascular PDAC cells and to 67 ± 4% in PDAC cells found in intratumoral blood vessels. In nonmalignant tumors, 12 ± 3% of the total tumoral cells examined were HIF-1α(+), and HIF-1α(+) cells decreased to 2 ± 0.3% in perivascular cells examined in the tumors. In conclusion, HIF-1α(+) cells in PDAC and nonmalignant pancreatic tumors differ not only in their amounts but also in their relation to intratumoral blood vessels. HIF-1α(+) cells usually are adjacent to intratumoral blood vessels in PDAC tumors, but are farther away from the vessels in nonmalignant pancreatic tumors.

Serum high mobility group box chromosomal protein 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: The role of high mobility group box chromosomal protein 1 in hepatocellular carcinoma is unknown. The aim of study was to evaluate contributions of high mobility group box chromosomal protein 1 in hepatocellular carcinoma, and analyse the correlation between high mobility group box chromosomal protein 1 and clinicopathologic outcomes. PATIENTS/METHODS: High mobility group box chromosomal protein 1 levels were analysed by Western blot analysis. Edmondson grade, TNM stage and the Cancer of the Liver Italian Program score were used as analysis variables. RESULTS: The serum high mobility group box chromosomal protein 1 levels in hepatocellular carcinoma (84.2 +/- 50.4 ng/ml) was significantly higher than those in chronic hepatitis (39.8 +/- 10.5 ng/ml), liver cirrhosis (40.2 +/- 11.6 ng/ml) and healthy control (7.0 +/- 5.9 ng/ml, p < 0.0001, respectively), and positive correlation were found between high mobility group box chromosomal protein 1 and alpha-fetoprotein (r = 0.952, p < 0.0001), and between high mobility group box chromosomal protein 1 and the size of tumour (r = 0.904, p < 0.0001). High mobility group box chromosomal protein 1 were significant differences among Edmondson grade I, II, III, IV; TNM stage I, II, III, IV and Cancer of the Liver Italian Program score 0-1 points, 2-4 points, > 4 points (p < 0.0001, respectively). CONCLUSIONS: These results suggest that high mobility group box chromosomal protein 1 may be a useful marker for evaluating the tumour stage and predicting prognosis in hepatocellular carcinoma. Targeting high mobility group box chromosomal protein 1 production or release might have potential approaches for hepatocellular carcinoma treatment.

[Radiosensitizing effects of Lycium barbarum polysaccharide for Lewis lung cancer].

The radiosensitizing effects of the Lycium barbarum polysaccharide (LBP) were observed by the model transplanted Lewis lung cancer on C57 BL mice. When LBP alone was administered, it was not obvious that LBP inhibited the growth of Lewis lung cancer. The significant radiosensitizing effects were obtained by combination of LBP and radiation. The mean numerical value of the dose modifying factors (DMF) was 2.05. The results also showed certain radiation enhancement effects of LBP to acute hypoxic cells of Lewis lung cancer. LBP presented few toxicity to the mice.

Hypocholesterolaemic effects of dietary propionate: studies in whole animals and perfused rat liver.

In adult male rats fed a non-purified diet supplemented with 5% sodium propionate, plasma cholesterol concentrations were significantly depressed. Although liver cholesterol was increased by feeding propionate, rates of hepatic cholesterol and fatty acid synthesis were unchanged. Tissue concentrations and rates of synthesis of cholesterol were also unaffected by dietary propionate in stomach, small intestine and caecum. Concentrations of propionate in hepatic portal venous plasma were raised by feeding the supplemented diet but the increase was low in comparison to the dietary intake. Examination of the gut contents revealed concentrations of total volatile fatty acids (VFA) of 19 mumol/ml in the stomach contents of control rats and 148 mumol/ml (of which propionate contributed 116 mumol/ml) in those fed the supplemented diet. Duodenal and ileal concentrations of VFA were very low and were only slightly raised in the propionate-fed rats while caecal VFA were the same in both groups with a combined mean of 159 mumol/ml. These data indicate that in the rat, the absorption of dietary propionate appears to occur in the stomach. In pigs fed a standard ration hepatic portal venous VFA remained low for the first 4 h after feeding but then rose with the onset of large bowel fermentation. Feeding the diet supplemented with propionate caused hepatic portal venous plasma concentrations to rise by approximately 0.4 mumol/ml. This increase was apparent 30 min after feeding and was sustained for 3 h but subsequently there was no difference to controls. As in the rat, the absorption of dietary propionate appeared to occur in the upper gastrointestinal tract. The transport of propionate via the porcine hepatic portal vein also appeared insufficient to account for the dietary intake and suggests metabolism of the acid by the upper gastrointestinal tract. Further studies with perfused livers from fed rats indicated that propionate at a concentration of 1 mumol/ml did not alter cholesterol synthesis but that inhibition occurred at 18 mumol of propionate/ml. It appears that a redistribution of cholesterol from the plasma to the liver, rather than inhibition of hepatic and intestinal cholesterol synthesis, is responsible for the hypocholesterolaemic effects of dietary propionate. Because the absorption and transport of dietary propionate appears to follow a time course which differs considerably to that of the acid produced by the large bowel microflora, we conclude also that VFA produced by such fermentation would not seem to be responsible for the hypocholesterolaemic effects of certain water-soluble plant fibres.

Adherence patterns and DNA probe types of Escherichia coli isolated from diarrheal patients in China.

One hundred and seventy-two strains of Escherichia coli isolated from diarrheal patients in Beijing, P.R. China, were analyzed for plasmid DNA profile, HEp-2 cell adherence ability and reactivity to 10 previously described DNA probes. They had not been recognized as pathogenic E. coli in China. Of the 110 strains tested, 76 (69%) contained one or multiple large plasmids. Of the 71 strains with the large plasmids 64 could adhere to HEp-2 cells. Of the 172 strains, 102 (59.3%) were hybridized with at least one of the 10 probes. Of those, seven strains hybridized with enteroaggregative E. coli (EAggEC) probe. Their serotypes were O128 (two strains), O6 (one strain), and O111 (one strain). Three strains were untypable. Six and three strains were hybridized with enteropathogenic E. coli (EPEC) attaching and effacing genes (eae) or EPEC adherence factor (EAF) probe, respectively. Two non-O157: H7 strains hybridized with enterohemorrhagic E. coli (EHEC) probe. Seventy-two strains (41.9%) hybridized with shiga-like toxin 2 or 1 (SLT2 or SLT1) probes. Among the SLT1 or SLT2 probe-positive strains, 54 hybridized with invasive (INV) plasmid probe developed for identification of enteroinvasive E. coli (EIEC) and Shigella species. The INV and SLT probe-positive strains might represent a new variety of verotoxin-producing E. coli (VTEC).