| Diabetes(Diabetes Mellitus, DM) andgastric cancer(Gastric Cancer, GC) are two kinds of multi-factorial and chronic diseases with high risk rate and strong heterogeneity. A growing number of epidemiologic studies have examined that DM patientshave a significantly increased risk of liver cancer, pancreatic cancer,colorectal cancer and other digestive malignant tumors, but the possible associations between diabetes mellitus(DM) and gastric cancer(GC)are inconclusive. Because of the large diabetic population base and large number of potential patients, even slight the association between diabetes and gastric might have a significant impact in the treatment and prevention.We conducted a meta-analysis and experimental research to assess the evidence regarding the associations and potential mechanisms between diabetes and incidence of gastric cancer.Part 1. Type 2 diabetes patients with gastric cancer susceptibility :A meta-analysis of cohort studiesObjective:In the past decades significant epidemiological evidence has been amassed to suggest that diabetes and cancer are associated, and the link appears causal. However, the epidemiological evidence is not conclusive for gastric cancer.Nowadays epidemiological studies clearly indicate that the risk of gastric cancer may be increased in diabetic patients. Especially some countries in East Asia which place is prevalence of gastric cancer. Consequently, it is really significant to systematically evaluate the association between type II diabetes and incidence of gastric cancer.Methods:We searched Pub Med, Embase, Cochrane Library and ISI web of knowledge without any limitations with respect to publication date or language, we also searched the references of qualifying articles. All kinds of cohort studies comparing the risk of gastric cancer between diabetic patients and control subjects were included. We excluded studies that investigated only mortality but not incidence.25 studies met our criteria, and the qualities of these studies were evaluated using the Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were carried out with STATA software version 12.0.Results: A random-effects model meta-analysis showed an increased gastric cancer risk in diabetic patients(RR= 1.20,95%CI:1.12-1.28). Subgroup analyses indicated that this result persisted in studies of both male(RR =1.15,95%CI:1.02-1.29) and female(RR = 1.29,95%CI: 1.09-1.53),in studies of type Ⅰ(RR=2.20,95%CI:1.45-3.35) and typeⅡ(RR=1.20,95%CI:1.12-1.31)DM.Conclusions: Diabetes mellitus may increase the risk of gastric cancer by approximately 20%, it is maybe an independent risk factor for gastric cancer. This effect seems to be significant in typeⅠand female.Part 2.Effect and potential mechanisms of liuweidihuang pill on gastric cancer induced by MNU in db/db miceObjective : To establish mice model with gastric carcinomainduced by N-methyl-N-nitrosourea(MNU) and investigate the influence of diabetes on incidence of gastric cancer. And then research the preventive effects of liuwei dihuang pills on gastric cancer and its potential mechanism during the tumorigenesis of stomach.Methods : 44 four-week-old male C57BL/Ks J-db/db mice were randomly divided into four groups, including blank control group, disease model group, liuwei dihuang pills group and metformin group, to induce gastric cancer model by giving N-Methyl-N-Nitrosourea(MNU) every other week for 20 weeks. One week after completion of MNU administration, mice were given distilled water and liuwei dihuang pills dissolved in distilled water for 10 weeks. After that, mice were euthanised using 10% pentobarbital sodium. Final diagnoses were made after histopathological examination. ELISA method to detect the expression of serum IGF 1 and insulin, quantitative Real time PCR was performed using specific primer sets that amplify IGF 1 IGF-1R 及 insulin m RNA of stomach tissue and IL-6,IL-1β,IL-10,IL-18,TNF-α and IFN-γ m RNA to assess its relative expression ratio.Result: Similar to metformin group, liuwei dihuang pills can improve blood sugar and reduce the weight, and only 10% mice had chronic gastritis in the liuwei dihuang pills group, without tumor formation. While 67% mice had chronic gastritis in disease model group together with two gastric cancer. There are statistically significant differences(P<0.05) on gastric tumorigenesis between the the liuwei dihuang pills group and disease model group. ELISA test results showed that the liuwei dihuang pill and metformin can reduce the serum levels of insulin and IGF 1(P<0.05) in diabetes mice. Outcomes of quantitative Real time PCR showed that the liuwei dihuang pill and metformin can both reduce significantly the expression of In R and IGF-1R m RNA in stomach tissue(P<0.05). While only liuwei dihuang pill can reduce the expression of IGF-1m RNA with significant difference(P<0.05).Besides, the liuwei dihuang pill and metformin can both reduce significantly the m RNAs expression of inflammatory factors related to gastric cancer(1L-6, 1L-1β)in stomach tissue(P<0.05 or P<0.01). Especially, the expression of TNF-α in the liuwei dihuang pill group was down regulated to 58%. There was no difference between these four groups on the expression of IL-18, and IFN-γ m RNA.Conclusion: Liuwei dihuang pill can reduce the occurrence riskof gastric cancer in diabetes mice through inhibiting the serum levels ofinsulin and IGF 1 and the expression of inflammatory factorsrelated to gastric cancer m RNAs in db/db mice.Liuwei dihuang pills may be useful in preventing of gastric tumorigenesis in diabetic mice. |
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