News about Health (Part 6)

Chemoprevention of Lung Cancer in Transgenic Mice: Lung tumors

The incidence of lung tumors in all four groups of treated mice was 100%. p53+/-Ink4a/Arf+/+, and p53+/-Ink4a/ Arf+/- mice carrying a mutant p53 transgene (Val135) with or without Ink4a/Arf heterozygous deletion had a higher number of lung tumors (an average of 25 tumors per mouse) after treatment with benzo(a)pyrene than wild-type and p53+/+Ink4a/Arf+/- mice (an average of 12.0 tumors per mouse). More interestingly, mice with p53-dominant negative mutation and Ink4A/Arf heterozygous deficiency (p53+/-Ink4a/Arf+/-) exhibited a striking increase in tumor volume (approximately 23-fold) compared to a ninefold increase in tumor volume in mice with only the p53-dominant negative mutation (p53+/-Ink4a/Arf+/+). There was also an approximate 50% and an approximate fourfold increase in tumor volume in Ink4a/Arf heterozygous-deficient mice (p53+/+Ink4a/Arf+/-), indicating that the effect of Ink4A/Arf heterozygous deficiency is mostly on late-stage lung tumor progression. In addition, most of the lung tumors (approximately 60%) from mice with a p53 mutation and deletion of Ink4A/Arf (p53+/-Ink4a/ Arf+/-) were lung adenocarcinomas. In contrast, lung adenocarcinomas were seen in < 10% of the lung tumors from the wild-type mice, and approximately 50% of the lung tumors from either p53 transgenic mice or Ink4a/Arf heterozygous-deficient mice. These results clearly indicate a significant synergistic interaction between the presence of a mutant p53 transgene and the Ink4A/Arf deletion during lung tumor progression.

Chemoprevention of Lung Cancer in Transgenic Mice: Transgenic Mouse Model for Lung Adenocarcinomas

Chemoprevention of Lung Cancer in Transgenic Mice: Transgenic Mouse Model for Lung AdenocarcinomasAlthough the A/J mouse lung adenoma model is valuable because of similar histology to a subtype of human adenocarcinoma, there are some features yet to be desired in order to make this model better. For example, the progression of lung adenomas to adenocarcinomas is rare in A/J mice. The most common genetic alteration associated with these tumors being carcinogen-specific mutations is K-ras. The limited number of large adenocarcinomas produced in this model has been shown to produce characteristic LOH changes. However, even most of these larger adenocarcinomas do not show mutations or loss of the p53 tumor suppressor gene or lost expression of the cyclin D1/cyclin D kinase inhibitor p16 gene, although these or closely related genes are routinely altered in human lung cancer. In order to incorporate these specific alterations into the A/J tumor model, we placed two different transgenes onto the A/J background. canadian pharmacy

Chemoprevention of Lung Cancer in Transgenic Mice: Use of A/J Mice in Chemoprevention Studies

The A/J mouse lung model of chemical carcinogenesis has been the most frequently employed murine model both for testing for potential chemical carcinogens and to screen for agents that prevent carcinogenesis (chemopre-ventive agents). The model has been shown to respond to a wide variety of potential chemical carcinogens, including the tobacco-related carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene, yielding multiple peripheral adenomas. Among the agents tested in A/J mice, several groups of chemicals have shown significant efficacy against mouse lung tumor development.

Chemoprevention of Lung Cancer in Transgenic Mice

Chemoprevention of Lung Cancer in Transgenic MiceLung cancer is the leading cause of cancer deaths in men and women in the United States. Epidemiologic and laboratory animal model studies have demonstrated that smoking and environmental exposure to carcinogens are closely linked to increased lung cancer risk. Tobacco exposure has been implicated in 90% of lung carcinomas, and smokers have a 20-fold greater risk of acquiring lung cancer compared with persons who have never smoked. Although approximately one half of all people who had ever smoked are now former smokers, many people are unable or unwilling to stop smoking. For these reasons, chemoprevention is a potentially important approach to reduce the large number of tobacco-caused cancer deaths, especially for former smokers. Chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer.

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: Conclusion

There are several limitations in our study. First, the age and smoking history in pack-years of the control group were not exactly equivalent to the COPD patient group. Considering that some sub jects in the control group might subsequently acquire COPD, with or without additional smoking exposure, the possibility remains that the different background of the two groups could influence the results of the genotyping. Ideally, the age and smoking history of the two groups should be exactly matched. Then the results of genotyping would be more clearly differentiated between the two groups. Secondly, only a small number of smoker control subjects were successfully followed up for > 1 year, and we obtained dFEV1 data in a segment of this group. This was because they stopped visiting the clinic on cessation of smoking. Thirdly, data on HRCT parameters were not collected in the healthy smoker group because the facilities where the healthy smokers were recruited were not equipped with the same imaging technique that was available for the patients with COPD. If healthy smokers with Gc*1F allele could be shown to have larger dFEV1 and higher LAA% than those without the allele, our conclusion that the Gc*1F allele is related to the development of COPD would be more clearly substantiated. The role of this allele in the early development of COPD remains to be investigated. buy prozac online

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: FEV1/FVC

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: FEV1/FVCPrevious studies have shown that LAA% and sCLA correlated well with FEV1 percentage predicted and FEV1/FVC. In HRCT examinations, patients with Gc*1F allele had a higher LAA%, lower mean CT score, and larger sCLA than patients without the allele, whereas no difference was observed in the baseline FEV1 percentage predicted. This result may suggest that patients with the Gc*1F allele tend to acquire a more severe emphysema than patients without the Gc*1F allele. There have been few attempts to define a correlation between genetic factors and emphysematous changes in HRCT. HRCT is less frequently used in clinical practice for the management of COPD than pulmonary function tests. We suppose the reason may be due to its higher cost and lack of feasibility of setting up the equipment. Further investigation is needed to clarify whether Gc-globulin polymorphism contributes to an early development of pathologic emphysematous lesions that are difficult to detect by pulmonary function tests.

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele:

They concluded that the reason was due to the insufficient number of subjects needed to verify the hypothesis that Gc*1F homozygotes had an increased risk. These studies were based on white populations in which the frequencies of the three alleles were 0.16, 0.56, and 0.28 for Gc*1F, Gc*1S and Gc*2, respectively. It has been noted that the frequency of the Gc allele varies with ethnicity; in the Japanese population, it has been reported to be 0.49, 0.24, and 0.25 for Gc*1F, Gc*1S, and Gc*2, respectively. This distribution has a larger frequency of Gc*1F compared to that in whites. Our results and those of Ishii et al corroborate that Gc*1F homozygotes have an increased risk for COPD, at least in the Japanese population.

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: Discussion

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: DiscussionSimple linear regression analysis was used for studying correlations between LAA% and mean CT score. Mean CT score was linearly correlated with LAA% (R2 = 0.97, p < 0.001), with a simple linear regression model as follows: mean CT score (HU) = — 1.69 X LAA% — 842. Patients with mean CT score < — 940 HU were defined as having severe emphysema based on this model. Again, severely emphysematous patients with mean CT score < — 940 HU were more frequently seen in the Gc*1F( + ) group than in the Gc*1F( —) group (26 patients vs 0 patients, p < 0.0001; Fig 3). Additionally, sCLA was larger in Gc*1F( + ) patients than Gc*1F( —) patients (35.9 ± 26.2 pixels vs 22.7 ± 12.1 pixels, p = 0.004; Fig 4). There was no significant difference in total number of CLAs between the two groups (5,005 ± 2,117 vs 4,267 ± 2,135, p = 0.25). birth control pills

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: dFEV1

Follow-up pulmonary function data for calculating dFEV1 was available in 86 of the 103 patients with COPD, and 21 of the 88 smoker control subjects, There was no significant difference in age, smoking history, the baseline FEV1 percentage predicted, and the distributions of Gc-globulin allele between subjects with 1-year follow-up data and those without them in either patients with COPD or control subjects. The dFEV1 of patients with COPD (48.3 ± 62.7 mL) was significantly larger than that of control subjects (17.9 ± 32.5 mL, p < 0.0001). There were 17 RDs (20%) in the group of patients with COPD, whereas there were no RDs in the smoker control group (p = 0.03). There was no significant difference in dFEV1 between Gc*1F homozygotic patients and patients with other genotypes (54.9 ± 66.4 mLvs 45.5 ± 60.7 mL, p = 0.54); likewise, there was no significant difference in the frequency of RDs between the two groups (23% vs 20%, p = 0.78). In comparison of dFEV1 between patients with COPD and Gc*1F alleles [Gc*1F( + )] and patients with COPD without Gc*1F alleles [Gc*1F( —)], there were no significant differences in age, smoking history, and the baseline FEVX percentage predicted. However, the former group showed significantly larger dFEV1 than the latter group (53.8 ± 64.8 mL vs 20.2 ± 39.9 mL, p = 0.01). All of the 17 RDs were Gc*1F( + ) patients with COPD, and no RD was seen in Gc*1F( —) patients (p = 0.04). fully

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele: Pulmonary Function Testing

Pulmonary function tests were performed at the initial visit, and at each of the follow-up visits. The initial test values were used as the baseline data. When follow-up data were available > 1 year after the initial test, dFEV1 was obtained by subtracting the last follow-up FEV1 value from the baseline FEV1 value, and dividing by the time in years between the two tests (milliliters per year). At each clinic, all the lung function measurements were performed with consistency using the same type of electrospirometer; the Autospiro AS-600 (Minato Medical Science; Osaka, Japan) was used at the COPD clinic, and Chestac-65V (Chest; Tokyo, Japan) was used at the smokers’ clinic. In patients with COPD, the measurements were performed in their stable state, ie, there were no exacerbations of the conditions from the preceding 6 weeks. The use of bronchodilators was prohibited for at least 12 h before the tests were performed. The predicted values for pulmonary function were calculated based on the formula proposed by the Japan Society of Chest Diseases. Based on the previous studies, subjects who had a dFEV1 > 90 mL were defined as rapid decliners (RDs). more

Pages: Prev 1 2 3 4 5 6 7 8 9 10 ... 75 76 77 Next