8-epi-prostaglandin-f2alpha and Lung-Neoplasms

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2+/-10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9+/-5.0 pg/ml vs. 19.4+/-3.9 pg/ml, p<0.0001) and serum (44.5+/-6.3 pg/ml vs. 22.2+/-4.3 pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3+/-2.8 pg/ml vs. 2.3+/-0.7pg/ml, p=0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r=0.52, p=0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3+/-55.1 pg/ml vs. 180.5+/-14.7 pg/ml, p=0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9+/-3.6 pg/ml vs. 12.9+/-1.6 pg/ml, p=0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer.

Topics: Aged; Biomarkers, Tumor; Breath Tests; Dinoprost; Enzyme-Linked Immunosorbent Assay; Exhalation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

It has been hypothesized that the pathogenesis of lung cancer induced by cigarette smoking involves oxidative damage by free radicals. Epidemiological data on biomarkers of oxidative damage and risk of lung cancer development are sparse. A nested case-control study of 610 lung cancer cases and 610 matched controls was conducted within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2α (8-epiPGF2α), a biomarker of oxidative stress, were determined in baseline urine samples using a validated mass-spectrometry assay. Current smokers had significantly higher level of 8-epiPGF2α than former smokers or never smokers (P < 0.001). 8-epiPGF2α levels were significantly higher in lung cancer cases than their smoking-matched controls in former and current smokers, but not different in never smokers (P for interaction = 0.019). The relative risks of developing lung cancer for former and current smokers in the highest relative to the lowest quartile of 8-epiPGF2α were 5.25 (Ptrend = 0.035) and 1.99 (Ptrend =0.007), respectively. The effect of 8-epiPGF2α and biomarkers of cigarette smoke exposure on lung cancer risk was additive; the relative risk was 5.33 (95% confidence interval = 2.65-7.51) for current smokers with the highest thirds of 8-epiPGF2α and total cotinine compared with their lowest thirds. Smokers with a heightened state of oxidative stress in response to the insults of cigarette smoking may be more susceptible to smoking-induced lung carcinogenesis.

Topics: Biomarkers; Case-Control Studies; China; Dinoprost; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nicotiana; Oxidative Stress; Prospective Studies; Risk Factors; Smoke; Smoking

Urinary 8-isoprostane is an established biomarker for lipid peroxidation. However, the association between its pre-diagnostic levels and cancer incidence has rarely been evaluated.. 8793 older adults from the German ESTHER cohort were followed up for cancer incidence by cancer registry data. A directed acyclic graph was utilized to identify potential confounders. Multivariate Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI).. During 14-year follow-up, 1540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were detected. 8-isoprostane concentrations were positively associated with lung cancer, but not with cancer at the other sites. The HR (95% CI) for the association with lung cancer was 1.61 (1.10, 2.34) for comparison of the top with bottom tertile in total population. The association of 8-isoprostane levels with lung cancer persisted after the adjustment for smoking and other potential confounders and was multiplicative to the effect of smoking. However, 8-isoprostane levels did not improve lung cancer prediction when added to a model containing age, sex and smoking. A protective association of increasing 8-isoprostane levels was observed for prostate cancer incidence but this association was only statistically significant among current smokers.. Our findings suggest that lipid peroxidation is involved in the development of lung cancer. However, high oxidative stress may be a protective factor for prostate cancer, especially among current smokers.

Topics: Aged; Biomarkers; Breast Neoplasms; Colorectal Neoplasms; Dinoprost; Female; Follow-Up Studies; Germany; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Prognosis; Prospective Studies; Prostatic Neoplasms

DJ-1 is a multifunctional protein implicated in redox dependent cell fate decisions. The aim of our study was to determine the pleural fluid (PF) levels of DJ-1 in malignant pleural effusions (MPEs) secondary to lung cancer. Additionally, we opted to assess potential correlations of DJ-1 PF levels with the PF levels of superoxide dismutase-1 (SOD1) and 8-isoprostane that are known antioxidant enzymes and have been previously reported in MPEs.. Forty lung cancer patients with cytological proof of MPE were enrolled in this study. The PF levels of DJ-1, SOD1, and 8-isoprostane were measured by means of enzyme-linked immunosorbent assay.. The median PF levels of DJ-1 were 826 ng/mL (interquartile range, IQR: 482-1010 ng/mL). DJ-1 PF levels significantly correlated with PF Cu/Zn-SOD1 and PF 8-isoprostane levels (Spearman's rho, r; r = -0.476, P = 0.002 and r = -0.264, P = 0.033, respectively), PF lactate dehydrogenase (r = -0.497, P = 0.001) and total PF cell counts (r = -0.325, P = 0.041). Finally, in patients aged over 65 the PF DJ-1 levels were significantly higher than patients aged less than 65 (875 ng/mL vs. 607 ng/mL, respectively, P = 0.037).. To our knowledge, this is the first report to determine DJ-1's levels in MPEs due to lung cancer. The negative correlations between DJ-1, SOD1, and 8-isorpostane warrant further investigation regarding the altered redox regulation associated with MPEs.

Topics: Aged; Antioxidants; Cell Lineage; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; Male; Middle Aged; Oncogene Proteins; Oxidation-Reduction; Oxidative Stress; Pleural Effusion, Malignant; Protein Deglycase DJ-1; Superoxide Dismutase; Superoxide Dismutase-1

The aim of the study was to evaluate the exhaled breath condensate (EBC) levels of a valid oxidative stress marker, 8-isoprostane, before and after chemotherapy, in patients with non small cell lung cancer (NSCLC) in correlation with the extent of the disease and response to treatment.. Forty-five patients with inoperable NSCLC were initially enrolled in the study. Twenty-nine of them were finally evaluated in regards to 8-isoprostane levels in EBC before and after chemotherapy.. 8-Isoprostane levels were significantly lower after chemotherapy (p=0.014). Further analysis showed that the differences were mainly attributed: a) to the extent of the disease, with patients diagnosed with up to locally advanced disease (stages IB-IIIB) having significantly lower EBC 8-isoprostane levels post-chemotherapy (p=0.031); and b) to the response to treatment, with patients evaluated with partial response to treatment having significantly lower EBC 8-isoprostane levels post-chemotherapy (p=0.02).. In this prospective study, we showed that 8-isoprostane might represent a biomarker in NSCLC, reflecting both response to chemotherapy, as well as the extent of the disease.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carcinoma, Non-Small-Cell Lung; Dinoprost; Exhalation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxidative Stress; Prognosis; Treatment Outcome

8-Isoprostane (8-isoPGF2α) is a reliable marker and considered a gold standard for lipid peroxidation. There are very few reports of 8-isoprostane levels in cancer patients, and in patients undergoing chemotherapy. Oxidative stress is however expected and has been observed in patients with cancer. This study measured 8-isoprostane levels in urine by ELISA of 25 patients undergoing chemotherapy for advanced non-small cell lung cancer, at cycles 1, 2, and 3 of treatment. It considers the creatinine clearance of the patients, and correction of 8-isoprostane levels by creatinine clearance, and overnight urine volume methods. The average 8-isoprostane levels in urine increased more than 6 to 12 fold on chemotherapy treatment, from 532±587 pg/mL at cycle 1, 6181±4334 at cycle 2, and 5511±2055 at cycle 3. Similar results were obtained if 8-isoprostane levels were corrected for overnight urine volume, giving averages of 285±244 μg at cycle 1, 4122±3349 at cycle 2, and 3266±1200 at cycle 3. No significant difference was seen in average total overnight urine volume or number of urinations between chemotherapy cycles except for a large variation in urine volume between cycle 2 and 3. Creatinine levels were significantly different only between cycles 1 and 2 (p=0.016). In conclusion, cisplatin therapy has been shown to induce high levels of lipid peroxidation in lung cancer patients and can be assessed from the 8-isoprostane marker in overnight urine, with or without urine volume correction.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cisplatin; Creatinine; Dinoprost; Female; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Middle Aged; Oxidative Stress; Young Adult

Lung cancer is the leading cause of cancer death and oxidative stress secondary to carcinogens such as cigarette smoke has been implicated in its pathogenesis. Therefore, lung cancer patients were hypothesized to have higher levels of oxidative stress markers in their exhaled breath compared with controls.. Exhaled breath condensate (EBC) was collected from newly diagnosed subjects with non-small cell lung cancer (NSCLC) and control subjects in a cross-sectional observational study. The samples were then analyzed for hydrogen peroxide (H(2)O(2)), pH, 8-isoprostane, and antioxidant capacity.. A total of 71 subjects (21 NSCLC patients, 21 nonsmokers, 13 exsmokers, and 16 smokers) were recruited. NSCLC patients had significantly higher EBC H(2)O(2) concentration (NSCLC subjects versus smokers, 10.28 microM, 95% confidence interval [CI]: 4.74-22.30 and 2.29 microM, 95% CI: 1.23-4.25, respectively, p = 0.003) and lower antioxidant capacity (NSCLC versus smokers, 0.051 mM, 95% CI: 0.042-0.063 and 0.110 mM, 95% CI: 0.059-0.206, p = 0.023; NSCLC versus all controls as a group, 0.051 mM, 95% CI: 0.042-0.063 and 0.087 mM, 95% CI: 0.067-0.112, p = 0.001). They also had significantly lower pH (5.9, 3.3-7.3) compared with exsmokers (6.7, 5.8-7, p = 0.009).. The significant increase of H(2)O(2) and reduction in antioxidant capacity in the EBC of lung cancer patients further support the concept of the disequilibrium between levels of oxidants and antioxidants in lung cancer, which leads to increased oxidative stress. These findings suggest oxidative stress is implicated in the development of lung cancer and may be an early marker of the disease.

Topics: Aged; Antioxidants; Biomarkers; Breath Tests; Carcinoma, Non-Small-Cell Lung; Cross-Sectional Studies; Dinoprost; Female; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Lung Neoplasms; Male; Middle Aged; Oxidative Stress

The cytotoxic effects of blattellaquinone (BTQ), a sex pheromone produced by adult female German cockroaches, have been studied using human lung adenocarcinoma A549 cells. 1,4-Benzoquinone (BQ), a toxic chemical implicated in benzene toxicity, was used as a reference compound. Both BQ and BTQ showed comparable toxicity toward A549 cells, with LD50 values estimated to be 14 and 19 microM, respectively. These two compounds increased the formation of an oxidized fluorescent probe, 2',7'-dichlorofluorescein, but had no effect on the cellular GSSG level. Interestingly, BTQ increased the level of 8-epi-prostaglandin F2alpha and was 4-fold more efficient in depleting cellular GSH content than BQ. Of the five GSH adducts of BTQ isolated, three were identified as mono-GSH conjugates, and the other two were di-conjugates. Mass spectrometric and NMR analyses of the di-conjugates showed that the second GSH molecule displaced the isovaleric acid moiety, potentially via a nucleophilic substitution reaction. The ability of BTQ to conjugate a second GSH molecule without quinone regeneration indicated that it may be a more effective cross-linking agent than BQ. Future experiments may be needed to evaluate the overall safety of BTQ before the commercialization of the compound as a cockroach attractant.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Cockroaches; Dinoprost; Glutathione Disulfide; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Quinones; Reactive Oxygen Species; Sex Attractants