DNA and cell biology
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DNA and cell biology · Feb 2014
Significance of MDM2-309 polymorphisms and induced corresponding plasma MDM2 levels in susceptibility to laryngeal squamous cell carcinoma.
The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. Murine double-minute 2 (MDM2) oncoprotein plays a pivotal role in regulating p53, and the single-nucleotide polymorphism (SNP) 309T/G SNP in the promoter region of Mdm2 has been shown to be associated with increased risk of cancer. We investigated the association between Mdm2-309 promoter polymorphism, plasma MDM2 levels, and risk of laryngeal squamous cell carcinoma (LSCC). ⋯ Patients in advanced stages and with lymph node metastasis had higher plasma MDM2 levels, while the GT genotypes (308.06±18.9 pg/mL; p=0.037) had lower MDM2 plasma levels than the TT genotypes (369.00±25.2 pg/mL). The Mdm2 SNP309 G allele is implicated as an important LSCC and a vocal leukoplakia protective factor in the Chinese Han Population, and the proportion of GT genotype was lower in advanced LSCC patients and lymph node metastasis patients. Moreover, Mdm2-309 GT genotype patients had a lower plasma MDM2 level than the TT genotypes.
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DNA and cell biology · Oct 2012
ReviewUnderstanding histone deacetylases in the cancer development and treatment: an epigenetic perspective of cancer chemotherapy.
Cancer is a pathologic condition that involves genetic and epigenetic events culminating in neoplastic transformation. Alteration in epigenetic events that regulate the transcriptional activity of genes associated with various signaling pathways can influence multiple stages of tumorigenesis. In cancer cells, an imbalance often exists between histone acetyl transferase and histone deacetylase (HDAC) activities, and current research focuses actively on seeking competitive HDAC inhibitors (HDACi) for chemotherapeutic intervention. ⋯ Interestingly, it has been observed that cancer cells are more sensitive than nontransformed cells to apoptotic induction by some HDACi. Although the mechanistic basis for this sensitivity is unclear, yet HDACi have emerged as important epigenetic target for single and combinatorial chemotherapy. HDACi derived from diverse sources such as microbial, dietary, and synthetic increase acetylation level of cells and bring about anti-proliferative and apoptotic effects specific to cancer cells by way of their role in cell cycle regulation and expression of epigenetically silenced genes.
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DNA and cell biology · Jul 2012
Association of the -14C/G MET and the -765G/C COX-2 gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.
Chronic rhinosinusitis with nasal polyps is strongly associated with other diseases, including asthma and allergy. The following study tested the association of the -765 G/C polymorphism of cyclooxygenase-2 (COX-2) encoding gene and the -14C/G polymorphism of protooncogen MET (MET) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety-five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex-, age-, and ethnicity-matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. ⋯ Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the -765 G/C (OR 5.64; 95% CI 2.91-10.9 and OR 4.74; 95% CI 2.49-9.03, p<0.001, respectively) genotype of the COX-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that COX-2 and MET gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyp formation, which may also depend on asthma or allergy. Our results showed that the -765 G/C polymorphism of COX-2 gene and the -14C/G polymorphism of the MET gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.
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DNA and cell biology · Mar 2012
Differing effects of azithromycin and doxycycline on cytokines in cells from Chlamydia trachomatis-infected women.
Chlamydial infection of the lower genital tract usually spreads to the upper genital tract and is then responsible for more serious consequences, such as infertility, ectopic pregnancy, pelvic pain, and pelvic inflammatory disease. Genital infection with Chlamydia trachomatis and the resulting cytokine response largely determines the outcome of infection and disease. To date, studies showing comparative effects of azithromycin and doxycycline treatment for C. trachomatis infection in women with reproductive sequelae like infertility and their effect on immune molecules like cytokines are lacking. ⋯ However, in presence of doxycycline, inhibition of cytokines (IL-1β and IL-6) was only observed in stimulated cells from fertile women with primary C. trachomatis infection. The clinical efficacy of azithromycin was also better than doxycycline in recurrent C. trachomatis infection in women with complications such as infertility. Overall, this study suggests that azithromycin treatment with broader immunomodulatory effects may be preferable to doxycycline for the treatment of recurrent C. trachomatis infection associated with infertility.
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DNA and cell biology · Jun 2011
Tumor necrosis factor alpha and beta and interferon gamma gene polymorphisms in Turkish breast cancer patients.
Cytokine genes are important for researching cancer predisposition to cancers that elicit anti-tumor immune response. In this study, we investigated the association between breast cancer and tumor necrosis factor alpha (TNF-α) -308 (G>A), TNF-β +252 (A>G), and interferon gamma (IFN-γ) +874 (T>A) gene polymorphisms in a Turkish population. This study involved 204 female breast cancer patients and 204 healthy female controls. ⋯ In the composite genotype analysis, the TNF-α/β GAAG composite genotype (p = 0.0424), the TNF-α/IFN-γ GGTT and GATT composite genotypes (p = 0.0296 and p = 0.0129, respectively), the TNF-β/IFN-γ AGTT composite genotype (p = 0.0003), and the TNF-α/β/IFN-γ GGAGTT and GAAGTT composite genotypes (p = 0.0437 and p = 0.0038, respectively) were estimated to have a protective effect against breast cancer. However, the TNF-α/IFN-γ GGTA composite genotype is a risk factor for breast cancer (p = 0.0156). In conclusion, TNF-β +252GG genotype was found more frequent in Turkish breast cancer patients than controls and IFN-γ TA+AA genotypes were estimated to increase breast cancer risk significantly in Turkish population.