Targeting Gene-ViroTherapy for prostate cancer by DD3-driven oncolytic virus-harboring interleukin-24 gene.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in Western male population. Previous studies have demonstrated that differential display code 3 (DD3 or DD3(PCA3)) is one of the most PCa-specific genes; therefore, it has been used as a clinical diagnostic marker for PCa. In this study, we constructed an oncolytic adenovirus Ad.DD3-E1A by using the minimal DD3 promoter to replace the native viral promoter of E1A gene. In addition, Ad.DD3-E1A was armed with therapeutic gene IL-24 to enhance its antitumor activity. The resulting adenovirus, Ad.DD3-E1A-IL-24, demonstrated PCa specificity and excellent antitumor effect. Further analyses on its antitumor mechanism revealed that it has the capacity to induce apoptosis in PCa cells and inhibit angiogenesis. These results suggest that Ad.DD3-E1A-IL-24 is a promising antitumor agent that may be able to be used in the future as a treatment for PCa.

[Association of L-selectin gene polymorphism with susceptibility to coronary heart disease].

OBJECTIVE: To investigate the possible association between L-selectin gene P213S polymorphism and coronary heart disease (CHD) in Chinese population. METHODS: In total 212 CHD patients diagnosed by angiography and 230 healthy controls were studied. The genotype and allele frequencies of L-selectin gene polymorphism were assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of the L-selectin gene 213P allele in CHD patients was significantly higher than that in the control group (77.59% vs 69.35%, P=0.006). Compared with the SS genotype, PP homozygote had a significantly increased CHD risk (OR=2.70 and OR=2.15 using unadjusted and adjusted Logistic regression models, respectively). No association was found between the severity of CHD and the Lselectin gene P213S polymorphism CONCLUSION: Our findings suggest that L-selectin gene 213P mutant allele might contribute to susceptibility of Chinese individuals to contract CHD.

[Association of C-159T polymorphism in promoter region of CD14 and coronary heart disease].

OBJECTIVE: To investigate the distribution of CD14 promoter gene -159(C>T) polymorphism in Hubei Han population of China and analyze the association of CD14 polymorphisms with coronary heart disease (CHD). METHODS: Genotypes of CD14 were typed in 162 CHD patients and 196 controls by polymerase chain reaction-restriction fragment length polymorphism. Selected coronary angiography was performed in 162 CHD patients. RESULTS: CD14 promoter -159 genotype frequencies of CC, CT and TT were 27.4%, 45.6%, 27.0% and 14.8%, 46.5%, 38.7% in normal control group and CHD group respectively. Genotype distribution was in accordance with Hardy-Weinberg equilibrium. There existed statistically significant difference in frequencies of allele and genotype in CD14 C-159T polymorphism between CHD group and control group (Genotype: Chi2=0.654, P < 0.05, CT vs CC, OR=1.245, 95%CI: 1.001-1.473, TT vs CC, OR=2.374, 95%CI 2.012-2.649; Allele: Chi2=0.547, P < 0.05, T vs C, Chi2=0.547, P < 0.05, OR=3.105, 95%CI: 2.493-3.539). The distributions of allele and genotype in CD14 -159(C>T) were of statistically significant difference between non-myocardial infarction subgroup and myocardial infarction subgroup (Genotype: Chi2=0.782, P < 0.05, CT vs CC, OR=2.375, 95%CI: 2.017-2.689, TT vs CC, OR=3.459, 95%CI: 3.003-3.846. Allele: Chi2=2.374, P < 0.05, T vs C, Chi2=2.374, P < 0.05, OR=4.011, 95%CI: 3.814-4.279). However, no statistically significant difference was found among the subgroups of oneìtwo and three stenosed vessels. CONCLUSION: The T allele of the C-159T polymorphism of CD14 gene may be a risk factor for myocardial infarction.