Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

<p>Abstract</p> <p>Background</p> <p>Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.</p> <p>Methods</p> <p>Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.</p> <p>Results</p> <p>Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.</p> <p>Conclusions</p> <p>Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.</p

Bacterial and fungal microflora in surgically removed lung cancer samples

<p>Abstract</p> <p>Background</p> <p>Clinical and experimental data suggest an association between the presence of bacterial and/or fungal infection and the development of different types of cancer, independently of chemotherapy-induced leukopenia. This has also been postulated for the development of lung cancer, however the prevalence and the exact species of the bacteria and fungi implicated, have not yet been described.</p> <p>Aim</p> <p>To determine the presence of bacterial and fungal microflora in surgically extracted samples of patients with lung cancer.</p> <p>Materials and methods</p> <p>In this single-center prospective, observational study, tissue samples were surgically extracted from 32 consecutive patients with lung cancer, and reverse-transcription polymerase chain reaction (RT-PCR) was used to identify the presence of bacteria and fungi strains.</p> <p>Results</p> <p>The analysis of the electrophoresis data pointed out diversity between the samples and the strains that were identified. Mycoplasma strains were identified in all samples. Strains that appeared more often were Staphylococcus epidermidis, Streptococcus mitis and Bacillus strains, followed in descending frequency by Chlamydia, Candida, Listeria, and Haemophilus influenza. In individual patients Legionella pneumophila and Candida tropicalis were detected.</p> <p>Conclusions</p> <p>A diversity of pathogens could be identified in surgically extracted tissue samples of patients with lung cancer, with mycoplasma strains being present in all samples. These results point to an etiologic role for chronic infection in lung carcinogenesis. Confirmation of these observations and additional studies are needed to further characterize the etiologic role of inflammation in lung carcinogenesis.</p

Endoplasmic reticulum Ca2+-homeostasis is altered in small and non-small cell lung cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Knowledge of differences in the cellular physiology of malignant and non-malignant cells is a prerequisite for the development of cancer treatments that effectively kill cancer without damaging normal cells. Calcium is a ubiquitous signal molecule that is involved in the control of proliferation and apoptosis. We aimed to investigate if the endoplasmic reticulum (ER) Ca²⁺-homeostasis is different in lung cancer and normal human bronchial epithelial (NHBE) cells.</p> <p>Methods</p> <p>The intracellular Ca²⁺-signaling was investigated using fluorescence microscopy and the expression of Ca²⁺-regulating proteins was assessed using Western Blot analysis.</p> <p>Results</p> <p>In a Small Cell Lung Cancer (H1339) and an Adeno Carcinoma Lung Cancer (HCC) cell line but not in a Squamous Cell Lung Cancer (EPLC) and a Large Cell Lung Cancer (LCLC) cell line the ER Ca²⁺-content was reduced compared to NHBE. The reduced Ca²⁺-content correlated with a reduced expression of SERCA 2 pumping calcium into the ER, an increased expression of IP₃R releasing calcium from the ER, and a reduced expression of calreticulin buffering calcium within the ER. Lowering the ER Ca²⁺-content with CPA led to increased proliferation NHBE and lung cancer cells.</p> <p>Conclusion</p> <p>The significant differences in Ca²⁺-homeostasis between lung cancer and NHBE cells could represent a new target for cancer treatments.</p

High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation

<p>Abstract</p> <p>Background</p> <p>This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery.</p> <p>Methods</p> <p>Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests.</p> <p>Results</p> <p>Seventy-seven percent (482) had a smoking history while 11.3% (71) were current smokers. The length of smoking cessation to cancer diagnosis was <1 year for 56 (13.6%), 1-10 years for 110 (26.8%), 11-20 years for 87 (21.2%), 21-30 years for 66 (16.1%), 31-40 years for 44 (10.7%), 41-50 years for 40 (9.7%) and 51-60 years for 8 (1.9%). The mean cessation was 18.1 ± 15.7 years (n = 411 former smokers). Fifty-nine percent had stage 1 disease and 68.0% had adenocarcinoma. Squamous cell carcinoma was more prevalent in smokers (15.6% vs. 8.3%, p = 0.028); adenocarcinoma was more prevalent in never-smokers (79.9% versus 64.3%, p = 0.0004). The prevalence of adenocarcinoma varied inversely with pack year (p < 0.0001) and directly with years of smoking cessation (p = 0.0005).</p> <p>Conclusions</p> <p>In a surgical lung cancer cohort, the majority of patients were smoking abstinent greater than one decade before the diagnosis of lung cancer.</p

Decreased blood antioxidant capacity and increased lipid peroxidation in young cigarette smokers compared to nonsmokers: Impact of dietary intake

<p>Abstract</p> <p>Background</p> <p>Blood of cigarette smokers routinely displays decreased antioxidant capacity and increased oxidized lipids compared to nonsmokers. This is thought to be due to both chronic exposure to cigarette smoke in addition to low intake of dietary antioxidants, and is a routine finding in veteran smokers. No study to date has determined the independent and combined impact of dietary intake and cigarette smoking on blood antioxidant capacity and oxidative stress in a sample of young, novice smokers.</p> <p>Methods</p> <p>We compared resting plasma antioxidant reducing capacity (ARC; expressed in uric acid equivalents), serum trolox-equivalent antioxidant capacity (TEAC), whole blood total glutathione, plasma malondialdehyde (MDA), and plasma oxidized low density lipoprotein (oxLDL) between 15 young (24 ± 4 years), novice smokers (pack-year history: 3 ± 2) and 13 nonsmokers of similar age (24 ± 5 years). Detailed dietary records were maintained during a seven-day period for analysis of total energy, macro- and micronutrient intake.</p> <p>Results</p> <p>ARC (0.0676 ± 0.0352 vs. 0.1257 ± 0.0542 mmol·L^-1; mean ± SD, p = 0.019), TEAC (0.721 ± 0.120 vs. 0.765 ± 0.130 mmol·L^-1, p = 0.24) and glutathione (835 ± 143 vs. 898 ± 168 μmol·L^-1, p = 0.28) were lower in smokers compared to nonsmokers, with only the former being statistically significant. MDA (0.919 ± 0.32 vs. 0.647 ± 0.16 μmol·L^-1, p = 0.05) and oxLDL were both higher in smokers compared to nonsmokers (229 ± 94 vs. 110 ± 62 ng·mL^-1, p = 0.12), although only the MDA comparison was of statistical significance. Interestingly, these findings existed despite no differences in dietary intake, including antioxidant micronutrient consumption, between both smokers and nonsmokers.</p> <p>Conclusion</p> <p>These data, with specificity to young, novice cigarette smokers, underscore the importance of smoking abstinence. Future studies with larger sample sizes, inclusive of smokers of different ages and smoking histories, are needed to extend these findings.</p

Can an hour or two of sun protection education keep the sunburn away? Evaluation of the Environmental Protection Agency's Sunwise School Program

BACKGROUND: Melanoma incidence is rising at a rate faster than any other preventable cancer in the United States. Childhood exposure to ultraviolet (UV) light increases risk for skin cancer as an adult, thus starting positive sun protection habits early may be key to reducing the incidence of this disease. METHODS: The Environmental Protection Agency's SunWise School Program, a national environmental and health education program for sun safety of children in primary and secondary schools (grades K-8), was evaluated with surveys administered to participating students and faculty. RESULTS: Pretests (n = 5,625) and posttests (n = 5,028) were completed by students in 102 schools in 42 states. Significant improvement was noted for the three knowledge variables. Intentions to play in the shade increased from 68% to 75%(p < 0.001) with more modest changes in intentions to use sunscreen. Attitudes regarding healthiness of a tan also decreased significantly. CONCLUSIONS: Brief, standardized sun protection education can be efficiently interwoven into existing school curricula, and result in improvements in knowledge and positive intentions for sun protection

Are time-trends of smoking among pregnant immigrant women in Sweden determined by cultural or socioeconomic factors?

<p>Abstract</p> <p>Background</p> <p>The widening socioeconomic gap in smoking during pregnancy remains a challenge to the Swedish antenatal care services. However, the influence of cultural factors in explaining the socioeconomic differences in smoking during pregnancy is not clear among the immigrant women. The aim of this study was to investigate whether the development of smoking prevalence among pregnant immigrant women in Sweden followed the trajectory which could be expected from the stages of the global smoking epidemic model in the women's countries of origin, or not.</p> <p>Methods</p> <p>Delivery data on pregnancies in Sweden from 1982 to 2001 was collected from the Swedish Medical Birth Registry. From a total of 2,224,469 pregnant women during this period, all immigrant pregnant women (n = 234,731) were selected to this study. A logistic regression analysis and attributable fraction were used to investigate the association between smoking during pregnancy and the socioeconomic differences among immigrant women.</p> <p>Results</p> <p>Overall, the prevalence of smoking among pregnant immigrant women decreased from 30.3% in 1982 to 11.0% in 2001, albeit with remarkable differences between educational levels and country of origin. The greatest decline of absolute prevalence was recorded among low educated women (27,9%) and among other Nordic countries (17,9%). In relative terms, smoking inequalities increased between educational levels regardless of country of origin. The odds ratios for low educational level for women from other Nordic countries increased from 4.9 (95% CI 4.4-5.4) in 1982 to 13.4 (95% CI 11.2-16.2) in 2001, as compared to women with high education in the same group. Further, the total attributable fraction for educational difference increased from 55% in 1982 to 62% in 2001, demonstrating the strong effect of educational attainment.</p> <p>Conclusions</p> <p>Our hypothesis that the socioeconomic time trend of smoking based on the stage of the world wide tobacco epidemic model related to country of origin of the immigrant women was not supported by our analyses. Our findings does not support a call for specific "culture sensitive" antismoking policies or interventions in Sweden or similar countries, but reinforce the existing evidence with a focus on women with a low educational level, regardless of cultural background.</p

Multifunctional Role of Bcl-2 in Malignant Transformation and Tumorigenesis of Cr(VI)-Transformed Lung Cells

B-cell lymphoma-2 (Bcl-2) is an antiapoptotic protein known to be important in the regulation of apoptosis in various cell types. However, its role in malignant transformation and tumorigenesis of human lung cells is not well understood. We previously reported that chronic exposure of human lung epithelial cells to the carcinogenic hexavalent chromium Cr(VI) caused malignant transformation and Bcl-2 upregulation; however, the role of Bcl-2 in the transformation is unclear. Using a gene silencing approach, we showed that Bcl-2 plays an important role in the malignant properties of Cr(VI)-transformed cells. Downregulation of Bcl-2 inhibited the invasive and proliferative properties of the cells as well as their colony forming and angiogenic activities, which are upregulated in the transformed cells as compared to control cells. Furthermore, animal studies showed the inhibitory effect of Bcl-2 knockdown on the tumorigenesis of Cr(VI)-transformed cells. The role of Bcl-2 in malignant transformation and tumorigenesis was confirmed by gene silencing experiments using human lung carcinoma NCI-H460 cells. These cells exhibited aggressive malignant phenotypes similar to those of Cr(VI)-transformed cells. Knockdown of Bcl-2 in the H460 cells inhibited malignant and tumorigenic properties of the cells, indicating the general role of Bcl-2 in human lung tumorigenesis. Ingenuity Pathways Analysis (IPA) revealed potential effectors of Bcl-2 in tumorigenesis regulation. Additionally, using IPA together with ectopic expression of p53, we show p53 as an upstream regulator of Bcl-2 in Cr(VI)-transformed cells. Together, our results indicate the novel and multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of human lung epithelial cells chronically exposed to Cr(VI)