DNA and cell biology
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DNA and cell biology · Oct 2010
Comparative StudyAssociation of tumor necrosis factor gene polymorphisms with susceptibility to dilated cardiomyopathy in a Han Chinese population.
Tumor necrosis factor (TNF) is an immunomodulatory cytokine that plays an important role in many inflammatory and autoimmune diseases. We investigated the correlation between single-nucleotide polymorphisms of the TNF gene [i.e., TNF-α (308), TNF-α (857), TNF-α (863), TNF-α (1031), and TNF-ß (+252)] and dilated cardiomyopathy (DCM). A total of 110 DCM patients and 110 control subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism and DNA-sequencing assay. ⋯ Additionally, A allele of TNF-α (-308) and TNF-ß (+252) was associated with a 1.76-fold increased risk of DCM compared with G allele (OR=1.76; 95% CI, 1.05-2.95 and OR=1.79; 95% CI, 1.22-2.63, respectively). However,no association between DCM and TNF-α (857), TNF-α (1031), and TNF-α (863) was observed. TNF gene polymorphisms may be associated with risk of DCM.
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DNA and cell biology · Dec 2009
p53 gene expression and 2-methoxyestradiol treatment differentially induce nuclear factor kappa B activation in human lung cancer cells with different p53 phenotypes.
The p53 tumor suppressor gene is frequently mutated in multiple human cancers, leading to loss of wild-type p53 (wt-p53)-dependent functions and tumorigenesis. p53 gene therapy is used to induce apoptosis in human cancer cells and tumors. Activation of nuclear factor kappa B (NF-kappaB) causes resistance to both chemotherapy and apoptosis in tumor cells. We show that expression of wt-p53 from a recombinant adenovirus-p53 followed by treatment with 2-methoxyestradiol (2-ME), an endogenous, nontoxic, estrogenic metabolite, resulted in differential NF-kappaB activation and inhibitor kappaB alpha (IkappaB-alpha) degradation in three different human lung cancer cell lines with different p53 phenotypes. ⋯ In contrast, either adeno-p53 expression or 2-ME treatment induced NF-kappaB activation in the p53-deleted H1299 cells, but H460 cells, containing wt-p53, did not show NF-kappaB activation under any of these conditions. This shows p53-dependent differential signaling to NF-kappaB by 2-ME. Since NF-kappaB activation inhibits apoptosis and causes resistance to chemotherapy, our study suggests the need to distinguish p53 phenotypes of tumors for p53 gene and 2-ME therapy.
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DNA and cell biology · Nov 2005
ReviewDiversity and complexity of the mu opioid receptor gene: alternative pre-mRNA splicing and promoters.
Mu opioid receptors play an important role in mediating the actions of a class of opioids including morphine and heroin. Binding and pharmacological studies have proposed several mu opioid receptor subtypes: mu(1), mu(2), and morphine-6beta-glucuronide (M6G). The cloning of a mu opioid receptor, MOR-1, has provided an invaluable tool to explore pharmacological and physiological functions of mu opioid receptors at the molecular level. ⋯ So far we have identified 25 splice variants from the mouse Oprm gene, which are controlled by two diverse promoters, eight splice variants from the rat Oprm gene, and 11 splice variants from the human Oprm gene. Diversity and complexity of the Oprm gene was further demonstrated by functional differences in agonist-induced G protein activation, adenylyl cyclase activity, and receptor internalization among carboxyl terminal variants. This review summarizes these recent results and provides a new perspective on understanding and exploring complex opioid actions in animals and humans.
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DNA and cell biology · Oct 1999
Comparative StudyDNA priming-protein boosting enhances both antigen-specific antibody and Th1-type cellular immune responses in a murine herpes simplex virus-2 gD vaccine model.
It has previously been reported that herpes simplex virus (HSV)-2 gD DNA vaccine preferentially induces T-helper (Th) 1-type cellular immune responses, whereas the literature supports the view that subunit vaccines tend to induce potent antibody responses, supporting a Th2 bias. Here, using an HSV gD vaccine model, we investigated whether priming and boosting with a DNA or protein vaccine could induce both potent antibody and Th1-type cellular immune responses. When animals were primed with DNA and boosted with protein, both antibody and Th-cell proliferative responses were significantly enhanced. ⋯ DNA priming-protein boosting resulted in an increased IgG2a isotype (a Th1 indicator) profile, similar to that induced by DNA-DNA vaccination, whereas protein priming-DNA boosting caused an increased IgG1 isotype (a Th2 indicator) profile similar to that seen after protein-protein vaccination. This result indicates that preferential induction of IgG1 or IgG2a isotype is determined by the type of priming vaccine used. Thus, this study suggests that HSV DNA priming-protein boosting could elicit both potent Th1-type cellular immune responses and antibody responses, both of which likely are important for protection against HSV infection.
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DNA and cell biology · Apr 1996
ReviewHuman drug-metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer.
A growing number of human genetic polymorphisms in drug-metabolizing enzymes (DMEs) are being characterized. Some of these have been shown, quite convincingly, to be correlated with risk of toxicity or cancer, whereas others presently remain equivocal. There is good evidence that the correlation is stronger in populations exposed to a variety of environmental procarcinogens; perhaps 30% of DME substrates are able to be metabolically potentiated. ⋯ In some cases, the allelic frequencies vary dramatically between ethnic groups. In this review, our current knowledge about polymorphisms in the following genes are updated: the aromatic hydrocarbon receptor (AHR), the CYP1A1 structural gene (which encodes aryl hydrocarbon hydroxylase activity), the CYP1A2 structural gene (arylamine oxidations), the CYP2C19 gene (S-mephenytoin 4'-hydroxylase), the CYP2D6 gene (debrisoquine hydroxylase), the CYP2E1 gene (N,N-dimethylnitrosamine N-demethylase), the null mutant for the GSTM1 gene (glutathione transferase mu), and the NAT2 gene (arylamine N-acetyltransferase). If unequivocal biomarkers of genetic susceptibility to cancer and toxicity can be developed successfully, then identification of individuals at increased risk would be very helpful in the fields of public health and preventive medicine.