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Jing C.,The General Hospital of Chengdu Military Area | Yuan L.,The General Hospital of Chengdu Military Area | Xingguo P.,The General Hospital of Chengdu Military Area | Zhijie H.,The General Hospital of Chengdu Military Area | And 3 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011

Gliomas, with a poor clinical course, account for 30% to 40% of all intracranial tumors. Immunotherapy with monoclonal antibodies has emerged as a promising area of investigation and recently it has been shown that antibodies utilize complementarity-determining regions (CDRs) of their variable domains to bind to antigens with high affinity and specificity. Here, we designed an antibody mimetic fused with diphtheria toxin to target the U87 MG glioma cell line. VHCDR1 and VLCDR3, together with 5 amino acid residues on both side of the CDRs, through a cognate framework region (VHFR2) yielded a mimetic of BT32/A6 (United States Patent number: 5639863). We fused the mimetic with the first 388 amino acid residues of diphtheria toxin and E. coli strain BL21 (ED3) was used to express the soluble immunotoxin DT-MG. The immunotoxin DT-MG alone did not kill Raji up to the maximal concentration tested (10-6M) in vitro. By contrast, concentrations ≥10-9M, of the fused DT-MG killed more than 95% of U-87 MG cells. It is suggested that the mimetic maintained the synergic interactions and high-affinity associated with the parent antibody. This construct holds promise for targeting specific cancer epitopes and may be useful when incorporated into diagnostic and therapeutic regimens. Source


Chen J.,The General Hospital of Chengdu Military Area | Huang Z.-J.,The General Hospital of Chengdu Military Area | Duan Y.-Q.,The General Hospital of Chengdu Military Area | Xiao X.-R.,The General Hospital of Chengdu Military Area | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2012

Aim: The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake. Methods: A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathologicalexamination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification ofDNA and the MTHFR C677T genetic polymorphism was detected by PCRrestriction fragment-length polymorphism (PCR-RFLP). Results: The proportions of DNA hypermethylation in P16, MGMTandhMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue.The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and wasalso significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT,with OR (95% CI) of 2.03 (1.05-4.57). Conclusion: Our study found the P16, MGMT and hMLH1demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection. © The Korean Pain Society, 2012. Source


Jing C.,The General Hospital of Chengdu Military Area | Huang Z.,The General Hospital of Chengdu Military Area | Duan Y.,The General Hospital of Chengdu Military Area | Xiao X.,The General Hospital of Chengdu Military Area | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2012

Aim: An epidemiological study was conducted based on an esophageal cancer patient's cohort to investigate the association of folate intake and MTHFR C677T polymorphism with the prognosis of esophageal cancer in a Chinese population. Methods: 167 patients aged 37-75 years who had histological confirmed diagnosis of esophageal squamous cell cancer were collected from Jan. 2006 to Jan. 2008. MTHFR genotypes at the C677T site were analyzed by PCR-based RFLP methods, and the folate intake was computed by multiplying the food intake (in grams) and the folate content (per gram) of food in our questionnaire. Results: We found associations between the prognosis of esophageal cancer and smoking status, T and N stages. Individuals carrying the MTHFR 677CT and TT genotypes showed a shorter survival time than with the CC genotype, with adjusted HRs (95% CI) of 1.20 (0.56-2.15) and 2.29 (1.30-4.28), respectively. Similarly, those carrying MTHFR 677T allele had a 1.86-fold risk of death. A higher folate concentration showed a significant decreased risk of death, with an HR (95% CI) of 0.45 (0.18-0.87). Individuals with high folate intake and the MTHFR 677CC genotype showed a significant decreased risk of esophageal cancer (0.43, 0.25-0.89).Conclusion: Our findings supports the hypothesis that high folate intake and active MTHFR C677T polymorphism may exert protective roles in the prognosis of esophageal cancer in the Chinese population. Source


Chen J.,The General Hospital of Chengdu Military Area | Yuan L.,The General Hospital of Chengdu Military Area | Duan Y.Q.,The General Hospital of Chengdu Military Area | Jiang J.Q.,The General Hospital of Chengdu Military Area | And 3 more authors.
Genetics and Molecular Research | Year: 2014

Folic acid and methylenetetrahydrofolate reductase (MTHFR) may both affect the development of human cancer. We conducted a population-based case-control study in a Chinese population to investigate the potential role of folate intake and MTHFR gene polymorphisms in gastric cancer, and their interaction with infection by Helicobacter pylori and tumor location. A total of 767 patients with newly diagnosed gastric cancer and 775 controls were selected for this study. Genotyping of MTHFR C677T and A1298C was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System, and information on folate intake was collected by questionnaire. Compared with the CC genotype of MTHFR C677T, the TT genotype was significantly associated with a decreased risk of gastric cancer when the analysis was adjusted for other potential risk factors. We found a marginal significantly decreased risk of gastric cancer for individuals carrying the T allele [adjusted odds ratio (OR) = 0.83; 95% confidence interval (CI) = 0.65-1.01]. We detected an inverse relationship between folate intake and risk of gastric cancer, and the adjusted ORs (95%CI) for moderate and high folate intake were 0.97 (0.74-1.25) and 0.64 (0.49-0.87), respectively. Moreover, H. pylori infection, folate intake, and location of the tumor showed a significant interaction with the MTHFR C677T polymorphism. Our study suggests a protective role of MTHFR 677TT and high folate intake against gastric cancer, and the effect of the MTHFR C677T genotype may differ by H. pylori infection, folate consumption, and tumor site. © FUNPEC-RP. Source

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