Systematic Review Of The Therapies Including Thalidomide For Chinese Advanced Carcinoma Of Stomach And Establishment Of Acetaminophen Or Ethanol Induced Hepatotoxicity Model In Vitro

Objective:To investigate the effect of chemotherapy plus thalidomide for advanced carcimoma of stomach by systematic review. To establish acetaminophen(APAP) or ethanol induced hepatotoxicity model in vitro.Methods:All the relevant studies from the online databases such as CNKI were Located. Targeting studies for the review according to the criteria were selected and assessed. The date of response rate(WHO criteria or RECIST criteria), clinical benefit response(WHO criteria or RECIST criteria), one year survival rate, improvement rates of Karnofsky score and toxicity were analyzed by the meta analysis or vote counting. And it was also presented that the funnel flats and the result of the sensitivity analysis.In the study of establishing in vitro model, chang liver cell was incubated with APAP (5mM、10mM、20mM or30Mm) for18,24or48hours. We investigated the best condition for establishing the APAP induced hepatotoxicity model in vitro by MTT assay. Chang liver cell was incubated with ethanol(50mM、100mM、300mM or500mM) for24hours; Hep3B cell was incubated with ethanol (50mM or100mM) for24hours. We investigated the best condition for establishing ethanol induced hepatotoxicity model in vitro by MTT assay.Result:11studies were selected including580patients. Meta analysis results showed that comparing control group with treatment group(which using thalidomide), the Risk Ratio of response rate(WHO criteria) was1.45,95%CI (1.14,1.85)P=0.002; The Risk Ratio of clinical benefit response(WHO criteria) was1.42,95%CI (1.09,1.84), P=0.009; The Risk Ratio of response rate(RECIST criteria) was1.29,95%CI (0.97,1.72), P=0.08; The Risk Ratio of clinical benefit response(RECIST criteria) was1.49,95%CI(1.23,1.81), P<0.0001. The Risk Ratio of one year survival rate was1.16,95%CI (0.88,1.52) P=0.29. The Risk Ratio of improvement rate of Karnofsky score was1.59,95%CI (1.28,1.97) P<0.0001. The funnel plats showed that it was not sure there is no publishing bias. Comparison with control groups7studies showed that nausea and vomiting reduced(or symptom improved), which showed statistical significance;5studies showed that astriction increased (or symptom progressed), which showed statistical significance. Sensitivity analysis showed that the Risk Ratio of response rate (WHO criteria) and the Risk Ratio of clinical benefit response (RECIST criteria) were the same to the results of meta analysis in direction and also have statistical significance. One of the sensitivity analysis showed that there was no statistical significance of the improvement of the clinical benefit response (WHO criteria) and the improvement rate of Karnofsky score.It had been established that the APAP induced hepatotoxicity model on chang liver cell (Firstly, cell was hungered for24hours. And then cell was incubated with5mM or10mM APAP for24hours.); And it had also been established that the ethanol induced hepatotoxicity model on Hep3B cell (Firstly cell was hungered for24hours. And then cell was incubated with50mM or100mM ethanol for24hours.). The two hepatotoxicity models in vitro could be used for drug screening for the activity of hepatoprotective effect.Conclusion:Thalidomide pus chemotherapy increased the short-term effects and the toxicity was well tolerated for Chinese patients with advanced carcinoma of stomach. But one year survival rate was not improved. In addition, the improvement of improvement rate of Karnofsky score was necessary for further evaluation.It had been established that APAP or ethanol induced hepatotoxicity model in vitro by MTT assay. The models could be used for researching activity of hepatoprotective effect of varied drugs at the beginning of research, investigating the mechanism of hepatotoxicity and investigating:the mechanism of the Hepatoprotective effect from drugs.