CDH1 promoter polymorphism and stomach cancer susceptibility.

The relationship of stomach cancer susceptibility and the presence of E-cadherin (CDH1) promoter -160 C/A polymorphism had been reported with conflicting results. To further explore the association of this polymorphism with stomach cancer susceptibility, we performed an extensive search of relevant studies and carried out a meta-analysis to obtain a more precise estimate. A total of 16 studies including 2,611 cases and 3,788 controls were involved in this meta-analysis. When all studies involved, the meta-analysis results suggest no statistically significant association between CDH1 -160 C/A polymorphism and stomach cancer risk (CA vs. CC: OR = 1.01, 95% CI: 0.85-1.19; AA vs. CC: OR = 1.05, 95% CI: 0.75-1.46; dominant model: OR = 1.02, 95% CI: 0.86-1.20; recessive model: OR = 1.04, 95% CI: 0.76-1.41). When subgroup analyses were performed by ethnicity, the A-allele carriers conferred a decreased stomach cancer risk in Asians (AA vs. CC: OR = 0.67, 95% CI: 0.47-0.96; dominant model: OR = 0.85, 95% CI: 0.72-0.99), but no statistically significant association was found in Caucasians. In conclusion, this meta-analysis suggests that CDH1 -160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.

Traditional Chinese medicine Kang Xian Fu Fang I is effective for prophylaxis and treatment of alcoholic liver disease in rats.

BACKGROUND: Reversal of liver fibrosis is one of the key steps in the prevention and treatment of alcoholic liver disease (ALD), but the mechanism is unknown. This study was to investigate the effects of the Chinese medicine Kang Xian Fu Fang I (KXI) on prophylaxis and treatment of ALD in rats and its possible mechanism of action. METHODS: Eighty male Wistar rats were randomly divided into four groups: normal control; ALD model; treatment of ALD with KXI; and prophylaxis of ALD by KXI. At the end of 4, 8, 12 and 16 weeks, five rats from each group were anesthetized and their livers were removed for pathological studies using hematoxylin-eosin and Masson stain, immunohistochemical studies, and flow cytometry for matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Blood samples were taken for hyaluronic acid (HA) assay. RESULTS: Serum HA level and liver collagen content were lower in the groups given KXI for prophylaxis and treatment than in ALD model group (P<0.05). The levels of MMP-2 and MMP-9 were also decreased in the prophylaxis and treatment groups (P<0.05). Immunohistochemistry showed immunoreactive MMP-2 in endothelial cells of the hepatic artery and portal vein, sinusoidal endothelial cells, and sinusoidal cells. Immunoreactive MMP-9 occurred in the hepatic cells around the veins and sinusoidal cells. CONCLUSIONS: KXI can effectively inhibit or reverse the course of ALD. This may be attributable to its capacity to inhibit the expression of MMP-2 and MMP-9.

Loss of heterozygosity on 10q23.3 and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions.

AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.

Effects of ethanol on liver sinusoidal endothelial cells-fenestrae of rats.

BACKGROUND: Important advances have been made in research into the mechanism of alcoholic liver disease (ALD) over the past few years, but the role of liver sinusoidal endothelial cell (LSEC) in ALD has not been elucidated adequately. This study was undertaken to investigate the effect of ethanol on fenestrae of LSECs in rats. METHODS: A rat model of alcoholic liver disease was established by means of direct intragastric instillation of ethanol. Fifty-five rats of experimental (35 rats) and control (20) groups were sacrificed at the end of 4, 8, 12 weeks respectively, and also at the end of 12-week abstinence. After heart perfusion, the liver tissue was fixed and stained with hematoxylin and eosin for observation of serial changes of LSEC-fenestrae under a transmission electron microscope. RESULTS: Normal LESC was flat with a nucleus and organelles arranged regularly. The distal cytoplasm displayed as a lamina with many fenestrae, lacking the basement membrane(BM) underneath the endothelium. At the end of 4-week alcohol feeding, the number of fenestrae decreased at the distal cytoplasm in some LSECs, without the formation of the BM underneath the endothelium. At the end of 8 weeks, the number of fenestrae decreased significantly or even disappeared. The BM began to develop incompletely underneath the endothelium, while the active fibroblast appeared. At the end of 12 weeks, the number of fenestrae decreased more significantly and the complete BM could even be seen. But the changes were mostly limited in the single or adjoining sinus, and fibrosis was scarcely formed. At the end of 12-week abstinence, defenestration and formation of the endothelial BM lightened significantly. CONCLUSIONS: Defenestration and formation of the BM in LSECs develop gradually with the chronic stimulation of ethanol. Hepatic sinusoidal capillarization and fibrosis will be seen if their state is more serious. These early changes, i.e., limited and regional defenestration and capillarization may be the basis of alcoholic peri-fibrosis. This kind of hepatic fibrosis is reversible after removal of etiological factors.

[Deletion of p15 and pl6 genes and overexpression of STK15 gene in primary hepatocellular carcinoma].

OBJECTIVE: To investigate the association of p15 and pl6 genes deletion and STKI5 gene overexpression in primary hepatocellular carcinoma (PHC). METHODS: The carcinoma tissue and the adjacent normal tissue were taken from 30 PHC patients during operations who had had neither chemotherapy nor radiotherapy preoperatively. DNA was extracted from the tissues and PCR was used to determine the homozygous deletion of p15 exon2 (pl5E2) and pl6 exon 2 (pl6E2). RNA was extracted, cDNA was synthesized by RT-PCR, and the expression of STKI5 gene was tested by PCR. Beta-actin was used as an internal control. Average density value (ADV) of STK15 gene and that of beta-actin gene were determined in both carcinoma tissue and the adjacent normal tissue. RESULTS: The rate of p15E2 deletion was 13.3% (4/30) and the rate of p16E2 deletion was 16.7% (5/30) in the carcinoma tissue. The p15E2 and pl6E2 co-deletion rate was 6.7% (2/30). In 19 of the 30 cases (63.3%) the expression of STK15 gene in carcinoma tissue was higher than that in the adjacent normal tissue. The ratio of ADV of STK15 gene to ADV of beta-actin gene (1.53+/-0.31) in the carcinoma tissue was significantly higher than that (0.91+/-0.25) in the paired adjacent normal tissue (t = 2.86). CONCLUSION: The homozygous deletion of p15E2 and p16E2 and overexpression of STKI5 gene may play a role in the oncogenesis and malignant progression of PHC.

[The influence of alcohol on the liver sinusoids endothelial cell fenestrae of rats].

OBJECTIVE: To study the influence of alcohol on the liver sinusoids endothelial cell (LSEC) fenestrae of rats. METHODS: Setting up the rat model of alcoholic liver disease by orogastric administration of alcohol, then kill the experimental and control groups of rats at the end of 4 weeks, 8 weeks and 12 weeks after alcohol feeding, and also at the end of another 12 weeks after balance foods feeding succeeding with alcohol feeding for 12 weeks. Staining the liver tissue by means of HE method and observing the successive change of LSEC fenestrae by transmission electron microscope. RESULTS: The normal LSEC was flat with nucleus and organelle arranged regularly. The distal cytoplasm displayed as lamina with many fenestrae, not accompanied by basement membrane (BM) formation under the endothelial cell. At the end of 4 weeks of alcohol feeding, fenestrae decreased at the partial distal LSEC cytoplasm, but no BM developed. At the end of 8 weeks, fenestrae decreased significantly, even disappeared, with the BM developed incompletely under the endothelial cell. Concomitantly, fibroblast with active function developed. At the end of 12 weeks, the changes became more obvious; the complete BM could even be seen. However, this kind of changes was mostly limited in the single or adjoining sinusoids, as well as with little widespread formation of fibrosis. At the end of 12 weeks of stopping alcohol feeding, defenestrae and development of BM attenuated obviously. CONCLUSION: The defenestrae and BM of LSEC develop gradually with the chronic alcohol stimulation. Sinusoid capillarization and liver fibrosis even form when significant changes happen. The early change of the limited defenestrae and capillarization may be the basis of alcohol periportal fibrosis formation. This kind of liver fibrosis can be reversible after stopping alcohol feeding.