HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma

AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province.METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics.RESULTS: Allele frequency (AF) of HLA-DRB1·0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1·0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles.CONCLUSION: HLA-DRB1·0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1·0901may be susceptible to esophageal carcinoma.

Antitumor immunopreventive effect in mice induced by DNA vaccine encoding a fusion protein of α-fetoprotein and CTLA4

AIM:To develop a tumor DNA vaccine encoding a fusion protein of murine AFP and CTLA4,and to study its ability to induce specific CTL response and its protective effect against AFP-producing tumor.METHODS:Murine α-fetoprotein (mAFP) gene was cloned from total RNA of Hepal-6 cells by RT-PCR.A DNA vaccine was constructed by fusion murine α-fetoprotein gene and extramembrane domain of murine CTLA4 gene.The DNA vaccine was identified by restriction enzyme analysis,sequencing and expression.EL-4 (mAFP) was developed by stable transfection of EL-4 cells with pmAFP.The frequency of cells producing IFN-γ in splenocytes harvested from the immunized mice was measured by ELISPOT.Mice immunized with DNA vaccine were inoculated with EL-4(mAFP) cells in back to observe the protective effect of immunization on tumor. On the other hand,blood samples were collected from the immunized mice to check the functions of liver and kidney.RESULTS:1.8kb mAFP cDNA was cloned from total RNA of Hepal-6 cells by RT-PCR.The DNA vaccine encoding a fusion protein of mAFP-CTLA4 was constructed and confirmed by restriction enzyme analysis,sequencing and expression.The expression of mAFP mRNA in EL-4 (mAFP) was confirmed by RT-PCR.The ELISPOT results showedthat the number of IFN-γ-producing cells in pmAFP-CTLA4 group was significantly higher than that in pmAFP,pcDNA3.1 and PBS group.The tumor volume in pmAFP-CTLA4 group was significantly smaller than that in pmAFP,pcDNA3.1 and PBS group, respectively. The hepatic and kidney functions in each group were not altered.CONCLUSION: AFP-CTLA4 DNA vaccine can stimulate potent specific CTL responses and has distinctive antitumor effect on AFP-producing tumor.The vaccine has no impact on the function of mouse liver and kidney.

Analysis of TAP1 and TAP2 Polymorphism of Mother-Infant in Chinese Patients with Pre-Eclampsia

To analyze the polymorphism of TAP gene and the shared rates of alleles between mothers and their infants in Chinese patients with pre-eclampsia,TAP1 and TAP2 genotyping was performed by the amplification refractory mutation system-polymerase chain reaction(ARMS-PCR)in 42 patients,106 normal pregnant women,and their neonates.The allelic frequency of TAP and the alleles shared in maternal-fetus were compared and analyzed in the two groups.Our results showed that,with totally eight alleles of TAP1 and TAP2 examined in the samples,no significant difference was found in allelic frequencies between pre-eclampsia group and control group,as well as between mothers and their neonates.Similar finding was obtained in the comparison with shared alleles.In conclusion,our results do not support a role for the polymorphisms of TAP in the etiology of pre-eclampsia. Cellular & Molecular Immunology.2005;2(2):141-144.