Risk Factors For Digestive System Cancer And The Role Of Aptamer In Digestive System Cancer Diagnosis And Targeted Therapy

The first stage: We investigated the link between diabetes mellitus(DM)and hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC),hepatitis B virus(HBV)-related HCC risk,meanwhile,we evaluated the relationship between relevant factor of DM and HCV-related HCC and HBV-related HCC in China.Results are as follows in the first part: To examine the association between DM and HCC,we conducted a case–control study of 300 Chinese CHC patients with HCC,comparing to an age-and sex-matched control group of 517 CHC patients not diagnosed with HCC.Multivariate analyses comparing the risk of HCV-related HCC development in DM patients with and without liver cirrhosis revealed that the estimated AOR(95% CI)for those with liver cirrhosis was 5.60(2.25–13.96).However,the HCC risk decreased significantly with a later age of diabetes onset(AOR [95% CI],0.94 [0.89–0.99]).DM was associated with an increased risk for HCC development in treatment-na?ve CHC patients in China.Furthermore,liver cirrhosis and an early DM diagnoses further increased the risks of HCC development in patients diagnosed with both CHC and DM.We also found that DM was more prevalent among the individuals with HCC(16.1%)than among those without HCC(7.6%)in HBV patients.A multivariate analysis revealed that individuals with DM who were >50 years of age had a higher risk of HBV-related HCC than individuals with DM who were ≤50 years of age(AOR: 7.403;95% CI: 1.049–52.253).Furthermore,the HCC risk was significantly higher in male individuals(AOR: 12.688;95%CI: 1.384–90.638).In conclusion,DM could increase HCC risk either in HBV patients or HCV patients.Different DM relevant risk factor might influence HCC development.The second part: We developed a new As PC1-specific aptamer(PCA#1)by a procedure known as systematic evolution of ligands by exponential enrichment(SELEX)and exploited its role as a targeting ligand to deliver doxorubicin(Dox)to As PC-1 cells in vitro.Results are as follows in the second part: The selected 76-base nucleotide aptamer preferentially bound to As PC-1 pancreatic cancer cells but not to control cells.The aptamer PCA#1 was intercalated Dox molecules which conjugate aptamer-Dox(Ap DC)molecule.Biostability analysis showed that the Ap DC molecules are stable in serum.Functional analysis showed that Ap DC specifically targeted and released Dox within As PC-1 cells but not in control cells.In conclusion,these results suggest that our study demonstrated that PCA#1 Ap DC is a promising aptamer-targeted therapeutic that can specifically deliver and release a high doxorubicin payload in pancreatic cancer cells.