ABSTRACT
Objective Toinvestigatethepossibilityandquantitativerangeofpepsinogen(PG)usedas the screening marker of gastric cancer by detecting serum pepsinogen level in different gastric mucous pathologic status.Method ThelevelofserumpepsinogenⅠ(PGⅠ)andpepsinogenⅡ(PGⅡ)bytimeresolvedfluoro-immunoassay(TRFIA)in 64 chronic atrophic gastritis patients,63 gastric mucous atypical hyperplasia patients, 67 gastric cancer patients and 20 healthy volunteers were defeeted ,and the ratio of PGR(PGⅠ/PGⅡ)was calculated.Then the three kinds of diseases were graded.The data was analyzed between groups and sub-groups.Result ①Compared with normal control group,the median PGⅠvalues were 1 24.01 ,91 .23 and 71 .23 respectively,which were all lower than that of healthy group (1 52.00).There were significant differ-ences(Z=-2.52,P=0.01 7 0;Z=-3.42,P=0.001 4;Z=-3.57,P=0.000 9).The median PGR values were 7.61 ,5.21 and 4.32 respectively,which were also lower than that of healthy group,the differences were significant(Z=-2.98,P=0.002 9;Z=-3.1 7,P=0.000 2;Z=-2.89,P=0.000 1 ).The PGⅡlevel of these diseases were not significantly different with control group.②The serum PGⅠlevel of gastric mucous atypical hyperplasia and gastric cancer were reduced significantly in contrast with atrophic gastritis (Z =-3.42,P =0.001 4;Z=-3.62,P=0.000 9);the levels of PGⅡand PGR were varied without significance (P>0.05 );③The levels of PGⅠamong atrophy gastritis and gastric cancer subgroup have no significant difference(χ2 =2.86,P=0.41 4 3;χ2 =1 .67,P=0.1 36 8).But the level of PGⅠwas significantly different in gastric atypical hyperplasia(χ2 =0.83,P=0.043 0).It decreased in light and medium grade dysplasia and went up in severe grade dysplasia.The levels of PGⅡ and PGR were varied without significance(P>0.05).④The areas under the ROC curves performed by the PGⅠ and PGR from normal control group and atypical hyperplasia group were 0.782 and 0.831 respectively;The sensitivity and specificity of PGⅠ≤72.1 2 μg/L and PGR≤4.32 for gastric dysplasia were 89.48%and 76.31%respectively.Conclusion ①The level of PGⅠand PGR were decreased along with the seriousness of gastric pathological changes and probably regarded as the screening markers of gastric mucous malignant transformation.②Serum pepsinogen level is closely correlated with gastric precancerous lesion,PGI≤72.1 2 μg/L and PGR≤4.32 has better specificity and sensitivity for gastric atypical hyperplasia in this area.
ABSTRACT
Objective To analyze the role of a key intracellular signaling molecule GSK3β in hepatocyte apoptosis induced by endoplasmic reticulum stress (ERS).Methods Using mouse hepatoma cell lines(Hepa 1) as cell apoptosis model triggered by tunicamycin,an endoplasmic reticulum stress inducer.One hour before Hepa 1 apoptosis induced by tunicamycin,SB216763 specifically inhibited the activity of GSK3β.Living cells/apoptotic cells were detected using acetoxymethyl (AM)/propidium iodide (PI) staining; Furthermore,the measurement of lactate dehydrogenase(LDH) of cell culture supernatant to evaluate the apoptosis.We detect p-GSK3β,GSK3β,the ERS-related protein(GRP78,CHOP and caspase-12) and caspase-3,cleaved caspase-3 protein expression using Western blot.Results Endoplasmic reticulum stress induced by tunicamycin promotes GSK3β activity; Inhibition of GSK3β activity alleviates endoplasmic reticulum stress:the expression of GRP78,CHOP and caspase-12 expression are inhibited.At the same time,GSK3β activity inhibition significantly reduced the endoplasmic reticulum stress-induced apoptosis:compared to cell apoptosis model group,the intervention group of SB216763 showed that the level of LDH decreased significantly,and PI staining of apoptotic cells was also significant reduction.Western blot results showed that the inhibition of GSK 3 β activity reduced reactive cleaved caspase-3 protein.Conclusion GSK3β is an important signaling molecule in the apoptosis pathway induced by endoplasmic reticulum stress ;Endoplasmic reticulum stress promotes hepatocyte apoptosis by mediating GSK3β.
ABSTRACT
Objective: To observe the effect of telomerase-antisense DNA on apoptosis of hepatoma cells induced by arsenic trioxide, in an effort to look for a new anti-hepatic cancer agent with high efficiency, low cytotoxicity. Methods: We designed and synthesized a 20nt telomerase-antisense DNA targeting telomerase template and observed its influence on the telomerase activity of hepatoma cells. H-E staining, flow cytometry, and DNA agarose electrophoresis were used to study the preventive effect of telomerase-antisense DNA on hepatoma cells apoptosis induced by arsenic trioxide. Flow cytometry was used to detect the expression of Fas, Fas-L, and bcl-2. Results: Telomerase-antisense DNA (5 ?mol/L) effectively inhibited the telomerase activity of hepatoma cells after 24 hours (P