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@#[Abstract] Objective: To study the effects of ursolic acid cooperated with gemcitabine on proliferation and apoptosis of pancreatic cancer PANC-1 cells. Methods: Human pancreatic cancer cell line PANC-1 was cultured in vitro with ursolic acid and gemcitabine respectively; and MTT assay was used to determine the IC50 of ursolic acid and gemcitabine, thus obtaining the best drug concentration. Ursolic acid (2 µmol/L) and gemcitabine (0.2 µmol/L) alone or in combination was used to treat PANC-1 cells; trypan blue assay was used to test cell viability, and PI staining was used to examine the cell apoptosis; wound healing was used to detect the proliferation and migration of PANC-1 cells. The protein expressions of P-JNK, Bcl-2, IL-6, P-Stat 3, NF-κB and Cox-2 in cells of each treatment group were detected using Western blotting. Results: Both ursolic acid and gemcitabine could significantly inhibit the proliferation of PANC-1 cells, and the IC50 is 13.67 and 2.78 µmol/L, respectively; and the final concentrations were determined at 2 and 0.2 µmol/L for ursolic acid and gemcitabine, respectively. Compared with single drug treatment, the combined treatment exerted a more prominent cell proliferation inhibition effect ([46.47±5.07]% vs [78.38±8.65]%, [76.12±3.23]%, all P<0.05), apoptosis-induction effect ([39.78± 7.01]% vs [20.35±8.51]%, [20.35±8.51]%, all P<0.01) and migration inhibition effect (P<0.01) on PANC-1 cells. Western blotting showed that the combined treatment strongly inhibited Bcl-2 and IL-6 expression, accelerated P-JNK protein expression compared with single drug treatment. Conclusion: The synergistic effect of ursolic acid and gemcitabine enhanced the inhibition on proliferation, migration, and promoted cell apoptosis of human pancreatic cancer cell line PANC-1, the mechanism may be associated with inhibition of Bcl-2, Il-6, P-stat 3 proteins and promotion of P-JNK protein.
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Objective To evaluate the long-term immunogencity and effectiveness of live attenuated hepatitis A (HA) vaccine (H2 strain) after one dose injection, through a 15 years' follow up observation. Methods A total of 220 children with negative anti-HAV antibody (aged 1-3 y)were involved and followed up in Jiaojiang district, Taizhou city, Zhejiang province. Indicators would include seroconversion and geometric meantiter(GMT) levels after inoculation the vaccine with single dose at 2 m, 12 m, 6 years, 10 years and 15 years. Epidemiological observation was carried out within the 15 years to evaluate the relationship between vaccine coverage, the incidence of HA and the overall effectiveness. In the studied population, serum was tested by ELISA(calibrated by WHO international reference) and ABBOTT Axsym HAVAB mEIA. Results Seroconversion rates were found to be 98.6% and 81.3% after 2 months and 15 years of inoculation and slowly decreased. GMT level was 128 mIU/ml after 15 years, significantly higher than the required protective level of 20 mIU/ml,recommended by WHO experts. Effectiveness through the 15-year follow up program showed a significant correlation between vaccine coverage and incidence of HA in 1-15 years aged group (Kendall-Rank test, t =-0.931, P＜0.01). There was no HA case seen among the observed accumulated 236 413 person-year vaccines, compared to 4 HA cases discovered in the 27 206 personyear of the non-vaccinees. The overall protective rate reached 100%. Through a mass vaccination program on children, the whole population established an immune-defence to enable the incidence of HA decreased by 96.7%. Conclusion The long-term immunogencity and effectiveness of live attenuated hepatitis A vaccine (H2 strain) after one dose injection could last as long as 15 years.
ABSTRACT
<p><b>BACKGROUND</b>Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization.</p><p><b>METHODS</b>A total of 220 children with negative anti-HAV antibody (aged 1 - 3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre (GMT) level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay.</p><p><b>RESULTS</b>Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years.</p><p><b>CONCLUSIONS</b>Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination.</p>