Previous studies have suggested that glutathione S-transferase (GST) genotypes may play a role in determining susceptibility to cervical cancer, though the data have often been conflicting. The objective of this study was to examine the effect of GSTP1 polymorphism on cervical carcinogenesis. The studied subjects, patients who were pathologically diagnosed with invasive cervical cancer yielding positive results for human papillomavirus (HPV) (n=342), were compared to healthy, normal, female controls (n=707). DNA from peripheral blood samples from studied subjects whose GSTP1 specific sequences had been determined by PCR with allele-specific primers were reviewed in comparison with the normal controls. The genetic susceptibility of GSTP1 (11q 13.1) in cervical carcinogenesis was determined by examining the effect of gene and environmental factors by the different histopathologic types of invasive cervical cancers. In assessing polymorphism GSTP1, the percentages of individuals homozygous for the A allele, homozygous for the G allele, and heterozygous for the two alleles were 66.8%, 3.9%, and 29.3%, respectively, in the control group, and 64.3%, 4.1%, and 31.6%, respectively, among in women with cervical cancer. Compared with GSTP1 G allele positive (GA or G/G), the odds ratio (OR) (95% confidence interval) for GSTP1 A/A was 1.0 (0.7 - 1.4) for invasive cervical cancer. However, the risk increased with GSTP1 A/A among ever smokers (3.9, 1.7 - 8.9, p-value=0.0012) compared with GSTP1 G allele positive among nonsmokers. In particular, this risk was higher among women with squamous cell carcinoma (4.7, 2.0 - 10.8, p=0.0003). Polymorphism of GSTP1 among smoking women was associated with a higher risk of developing cervical cancer.
Adult ; Aged ; Cervix Neoplasms/*etiology/genetics ; Female ; Glutathione Transferase/*genetics ; Human ; Isoenzymes/*genetics ; Loss of Heterozygosity ; Middle Age ; Polymorphism (Genetics) ; Risk ; Smoking

Tumor hypoxia contributes to the progression of a malignant phenotype and resistance to ionizing radiation and anticancer drug therapy. Many of these effects in hypoxic tumor cells are mediated by expression of specific set of genes whose relation to therapy resistance is poorly understood. In this study, we revealed that DNA-dependent protein kinase (DNA-PK), which plays a crucial role in DNA double strand break repair, would be involved in regulation of hypoxia inducible factor-1 (HIF-1). HIF-1beta-deficient cells showed constitutively reduced expression and DNA-binding activity of Ku, the regulatory subunit of DNA-PK. Under hypoxic condition, the expression and activity of DNA- PK were markedly induced with a concurrent increase in HIF-1alpha expression. Our result also demonstrated that DNA-PK could directly interact with HIF- and especially DNA-PKcs, the catalytic subunit of DNA-PK, could be involved in phosphorylation of HIF-1alpha, suggesting the possibility that the enhanced expression of DNA- PK under hypoxic condition might attribute to modulate HIF-1alpha stabilization. Thus, the correlated regulation of DNA-PK with HIF-1 could contribute to therapy resistance in hypoxic tumor cells, and it provides new evidence for developing therapeutic strategies enhancing the efficacy of cancer therapy in hypoxic tumor cells.
Antibodies/immunology ; Cell Hypoxia ; Cell Line, Tumor ; DNA Helicases/immunology/metabolism ; DNA-Binding Proteins/genetics/*metabolism/*physiology ; Deferoxamine/pharmacology ; Drug Resistance, Neoplasm/*physiology ; Humans ; Immunoprecipitation ; Neoplasms/enzymology/*metabolism ; Nuclear Proteins/genetics/*metabolism/physiology ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism/*physiology ; Research Support, Non-U.S. Gov't ; Transcription Factors/genetics/*metabolism/physiology ; Up-Regulation

BACKGROUND: The purpose of this study was to assess the effect of our new video-assisted asthma education program on patients' knowledge regarding asthma and asthma control. METHODS: Adult asthmatics who were diagnosed by primary care physicians and followed for at least 1 year were educated via smart devices and pamphlets. The education sessions were carried out three times at 2-week intervals. Each education period lasted at most 5 minutes. The effectiveness was then evaluated using questionnaires and an asthma control test (ACT). RESULTS: The study enrolled 144 patients (mean age, 56.7±16.7 years). Half of the patients had not been taught how to use their inhalers. After participating in the education program, the participants' understanding of asthma improved significantly across all six items of a questionnaire assessing their general knowledge of asthma. The proportion of patients who made errors while manipulating their inhalers was reduced to less than 10%. The ACT score increased from 16.6±4.6 to 20.0±3.9 (p<0.001). The number of asthmatics whose ACT score was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude of improvement in the ACT score did not differ between patients who received an education session at least three times within 1 year and those who had not. The majority of patients agreed to the need for an education program (95.8%) and showed a willingness to pay an additional cost for the education (81.9%). CONCLUSION: This study indicated that our newly developed education program would become an effective component of asthma management in primary care clinics.
Adult ; Asthma* ; Education* ; Humans ; Nebulizers and Vaporizers ; Pamphlets ; Physicians, Primary Care ; Primary Health Care*