Outdoor air pollution and female lung cancer in Taiwan

To investigate the relationship between air pollution and female lung cancer, the authors conducted a matched case-control study using female deaths that occurred in Taiwan from 1994 through 2003. Data on all eligible female lung cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of women who died from causes other than cancer or diseases associated with respiratory problems. The controls were pair matched to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. A municipality-based aggregate index of long-term exposure to air pollution was created by dividing the annual average of the measured values for each pollutant by the National Ambient Air Quality Standard for that pollutant. The ratios for each pollutant were scaled to a 100-point scale and then averaged together to generate an index value representing the net burden of these pollutants, with each weighted equally. The subjects were divided into tertiles according to the levels of the index just described. Women who lived in the group of municipalities with highest levels of air pollution exposure index were at a statistically significant increased lung cancer risk compared to the group living in municipalities with the lowest air pollution exposure index after controlling for possible confounders (OR = 1.28, 95% CI = 1.02-1.61). The findings of this study warrant further investigation of the role of air pollutants in the etiology of lung cancer.     

Activation of MAP kinases by hexavalent chromium, manganese and nickel in human lung epithelial cells

Epidemiological studies indicate that workers who perform welding operations are at increased risk for bronchitis, siderosis, occupational asthma and lung cancer due to fume exposure. Welding fumes are a complex chemical mixture, and the metal composition is hypothesized to be an etiological factor in respiratory disease due to this exposure. In the present study, human lung epithelial cells in vitro responded to hexavalent chromium, manganese and nickel over a concentration range of 0.2-200 microM with a significant increase in intracellular phosphoprotein (a measure of stress response pathway activation). The mitogen-activated protein kinases ERK1/2, SAPK/JNK and p38 were activated via phosphorylation following 1-h exposures. Hexavalent chromium up-regulated p-38 phosphorylation 23-fold and SAPK/JNK phosphorylation 17-fold, with a comparatively modest 4-fold increase in ERK1/2 phosphorylation. Manganese caused a two- to four-fold increase in SAPK/JNK and ERK 1/2 phosphorylation, with no observed effects on p38 kinase. Nickel caused increased (two-fold) phosphorylation of ERK 1/2 only, and was not cytotoxic over the tested concentration range. The observed effects of welding fume metals on cellular signaling in lung epithelium demonstrate a potentially significant interplay between stress-response signaling (p38 and SAPK/JNK) and anti-apototic signaling (ERK 1/2) that is dependant on the specific metal or combination of metals involved.     

Biomonitorization of chromium,copper, iron,manganese and nickel in scalp hair from orthodontic patients by atomic absorption spectrometry

The study was aimed to assess Cu, Cr, Fe, Mn and Ni levels in human scalp hair from a broad population group treated with orthodontic appliances (n = 70) to determine, whether the concentration of a given metal was significantly influenced by the orthodontic treatment in comparison to control group (n = 56). Levels of metal compounds were determined by atomic absorption spectrometry. The mean, ranges, median and 5th and 95th percentiles of metals analyzed in hair that were hypothesized to be systemically absorbed from stainless steel, are provided. The influence of individual factors on metal concentrations was considered (gender, age), and inter-element interactions were studied by evaluation of correlation coefficients between elements, as well as by multiple regression analysis. Differences in the content of metals in hair were only significantly increased for Mn when compared to the control group, but their levels were of the same magnitude to other control populations, and consequently, no risks linked to the treatment have been found. The orthodontic treatment increased significantly Mn levels in young patients (<20 years old) when compared with control group. Scalp hair analysis is a good method to investigate the release of the elements from fixed orthodontic appliances.     

Ambient exposure to criteria air pollutants and female lung cancer in Taiwan

To investigate the relationship between air pollution and female lung cancer, the authors conducted a matched case-control study using female deaths that occurred in Taiwan from 1995 through 2005. Data on all eligible female lung cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of women who died from causes other than cancer or diseases associated with respiratory problems. The controls were pair-matched to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Classification of exposure to municipality air pollution was based on the measured levels of nitrogen dioxide and carbon monoxide. The results of the present study show that there is a significant positive association between the levels of air pollution and female lung cancer mortality. The adjusted odds ratios (95% confidence interval) were 1.24 (1.03-1.50) for the group with medium air pollution level and 1.46 (1.18-1.81) for the group with high air pollution level when compared to the group with the low air pollution level. Trend analyses showed statistically significant trend in risk of female lung cancer with increasing air pollution level. The findings of this study warrant further investigation of the role of air pollutants in the etiology of lung cancer.     

Dietary chromium and nickel enhance UV-carcinogenesis in skin of hairless mice

The skin cancer enhancing effect of chromium (in male mice) and nickel in UVR-irradiated female Skh1 mice was investigated. The dietary vitamin E and selenomethionine were tested for prevention of chromium-enhanced skin carcinogenesis. The mice were exposed to UVR (1.0 kJ/m(2) 3 x weekly) for 26 weeks either alone, or combined with 2.5 or 5.0 ppm potassium chromate, or with 20, 100 or 500 ppm nickel chloride in drinking water. Vitamin E or selenomethionine was added to the lab chow for 29 weeks beginning 3 weeks before the start of UVR exposure. Both chromium and nickel significantly increased the UVR-induced skin cancer yield in mice. In male Skh1 mice, UVR alone induced 1.9+/-0.4 cancers/mouse, and 2.5 or 5.0 ppm potassium chromate added to drinking water increased the yields to 5.9+/-0.8 and 8.6+/-0.9 cancers/mouse, respectively. In female Skh1 mice, UVR alone induced 1.7+/-0.4 cancers/mouse, and the addition of 20, 100 or 500 ppm nickel chloride increased the yields to 2.8+/-0.9, 5.6+/-0.7 and 4.2+/-1.0 cancers/mouse, respectively. Neither vitamin E nor selenomethionine reduced the cancer yield enhancement by chromium. These results confirm that chromium and nickel, while not good skin carcinogens per se, are enhancers of UVR-induced skin cancers in Skh1 mice. Data also suggest that the enhancement of UVR-induced skin cancers by chromate may not be oxidatively mediated since the antioxidant vitamin E as well as selenomethionine, found to prevent arsenite-enhanced skin carcinogenesis, failed to suppress enhancement by chromate.     

Plants as models for chromium and nickel risk assessment

The adverse effects of Cr(III), Cr(VI), and Ni(II) expressed as root and shoot growth inhibition, metal accumulation and translocation throughout plants, and genotoxicity study were examined. To examine phytoxicity and metal accumulation, Vicia sativa, Raphanus sativus, Zea mays and Sinapis alba plants were used. Except for S. alba root growth inhibition, Ni had the strongest inhibitory effect on root and shoot growth. The inhibitory rank order based on IC?? values was Ni(II) > Cr(VI) > Cr(III). Z. mays was the least sensitive to all metals. While the accumulation of Cr was higher in the roots than the upper plant parts, Ni transport to shoots was at least two times higher than that of Cr. The highest accumulation of Cr was found in Z. mays and that of Ni in V. sativa and Z. mays roots. For all plants, the translocation factor was higher for Cr(VI) than for Cr(III). The translocation factor for Ni was several times higher than those of Cr. For mutagenicity assay, root tips of V. sativa, R. sativus and Z. mays were used. All metals exerted a significant increase of chromosomal aberrations and the rank order of aberrations was: Cr(VI) > Ni(II) > Cr(III). Genotoxic effects of metals were also determined by analysis of micronuclei frequency in the pollen tetrads of Tradescantia plants. None of metals significantly stimulated micronuclei frequency and the genotoxic effect decreased in the following order: Cr(VI) ≥ Ni(II) > Cr(III).     

Accumulation of chromium in Chinese hamster V79-cells and nuclei

The bioavailability of carcinogenic compounds plays an important role in the process of oncogenesis. Chromium in its hexavalent oxidation state is classified as carcinogen to humans. Therefore we studied the uptake of chromate(VI) into Chinese hamster V79 cells and nuclei isolated after the incubation of the whole cells with chromate. The chromium content of cells and nuclei was determined by atomic absorption spectroscopy. Chromate is taken up in a concentration dependent manner and accumulates to about 30 fold over the extracellular concentration of 0.1 mmol/1. Incubating whole cells with the same concentration results in an intranuclear concentration of up to 6 mmol/1 after 3 h. The kinetic parameters (K_M = 0.34 mmol/1, V_max = 0.12 fmol per cell and minute) are in the same order of magnitude as previously published data. The consequences of the high intracellular and intranuclear concentrations are discussed in terms of the genotoxic effects.     

Accumulation and photodynamic activity of chlorin e6 in cisplatin-resistant human lung cancer cells

Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is one of the most potent anticancer drugs, but the emergence of acquired resistance to CDDP is a major problem in clinical settings. The purpose of this study was to investigate and compare the cellular accumulation and photodynamic activity of chlorin e6, a photosensitizer, in human lung cancer A549 cell line and its CDDP-resistant subline. First, we established the CDDP-resistant (A549/CDDP) cell subline with fourfold greater half-maximal inhibitory concentration value of CDDP on cell growth than that of the parent A549 cells. The cellular accumulation of chlorin e6 was temperature sensitive, and there were no significant differences in chlorin e6 accumulation between the two cell lines. The mRNA expression levels of ABCC1, ABCC2, and ABCG2 in A549/CDDP cells were comparable to those in A549 cells, whereas ABCB1 mRNA level was significantly higher in A549/CDDP cells than in A549 cells. In consistent with chlorin e6 accumulation, chlorin e6-mediated photodynamic activity on A549/CDDP cells was similar to that on A549 cells, whereas no cytotoxicity was observed when these cell lines were kept in dark. Our observations suggest that CDDP resistance has no significant influence on accumulation and photodynamic activity of chlorin e6 in A549 cells.     

吸烟及非吸烟肺癌患者的尿液代谢组学比较研究

目的探讨吸烟对肺癌患者体内代谢物质变化的影响。方法收集唐山市人民医院2012年9月-2017年9月诊治的60例肺癌患者尿液样本,其中发现数据集包括吸烟史20例,无吸烟史20例,验证数据集包括吸烟史10例,无吸烟史10例。采用LC-MS法对肺癌尿液样本进行非靶向代谢组学研究,利用主成分分析法(PCA)和偏最小二乘判别分析法(PLS-DA)进行多元统计学分析。结果本研究发现有吸烟史肺癌组与无吸烟史肺癌组患者的尿液代谢图谱存在显著差异,并检测到17个差异有统计学意义(P<0.05)的代谢特征离子。与无吸烟史肺癌组患者相比,有吸烟史肺癌组患者尿液中3种代谢特征离子含量显著上升,14种代谢特征离子含量显著下降,基于KEGG代谢通路富集分析并发现吸烟会影响肺癌患者体内的酪氨酸代谢通路。此外,本研究还采用独立验证数据集对发现的17个差异有统计学意义的代谢特征离子进行验证,发现这些差异代谢特征能够较好地区分吸烟与非吸烟肺癌患者组,其预测准确度达75%,灵敏度为80%和特异性为70%。结论吸烟肺癌患者呈现出不同于非吸烟肺癌患者的尿液代谢谱图特征,尿液中多种代谢物的含量显著改变表明吸烟会影响肺癌患者体内物质代谢,这为进一步实验与临床研究提供了一定的参考依据,并为实现吸烟与非吸烟肺癌患者的个体化精准医疗提供一定的指导。     

NAD(P)H: quinone oxidoreductase polymorphism and lung cancer in Taiwan

Lung cancer is one of the leading causes of death in Taiwan since 1996. Genetic variation in metabolic activation or detoxification enzymes has been associated with the occurrence of lung cancer. NAD(P)H:quinone oxidoreductase (NQO1) enzyme is a cytosolic two-electron reductase thought to be involved in bioactivation and detoxification of environmental carcinogens. The possible association between NQO1 genetic polymorphism and lung cancer risk was examined among 95 male smokers without cancer and 100 male smokers with lung cancer in Taiwan. There was no significant difference in the proportion of wild-type NQO1 among all cancer cases and controls. When cases were stratified according to histological subtypes, the wild-type NQO1 was more common in adenocarcinoma than in controls. The odds ratio was 2.93 (95% confidence interval, 1.23-7.02; p = .02). This is the first observation for the positive association of this locus with lung cancer in an Asian population. These results suggest that NQO1 polymorphism is an important genetic risk factor for lung adenocarcinoma among smokers in Taiwan.     

弥散加权成像在小细胞肺癌脑转移瘤诊断中的价值

目的:分析比较小细胞肺癌及非小细胞肺癌脑转移瘤在磁共振弥散加权序列中的特征,并结合相关文献进行分析,旨在进一步提高小细胞肺癌脑转移瘤诊断正确率,为临床治疗提供可靠依据。方法:回顾性分析30例小细胞肺癌及26例非小细胞肺癌脑转移瘤磁共振常规平扫、弥散加权成像影像特征,并对瘤周水肿、弥散表观系数值、相对扩散系数值结果进行统计学分析。结果:小细胞肺癌脑转移瘤周水肿轻微或无水肿,弥散加权序列呈现高信号,弥散表观系数值及相对扩散系数值低于非小细胞肺癌脑转移瘤。结论:小细胞肺癌脑转移瘤在弥散加权成像中具有重要特征,正确认识可以提高小细胞肺癌脑转移瘤诊断正确率。     

Nitrates in drinking water and the risk of death from childhood brain tumors in Taiwan

The objective of this study was to (1) examine the relationship between nitrate (NO?-N) levels in public water supplies and risk of death from childhood brain tumors (CBT) and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of NO?-N on development of CBT. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to CBT and exposure to NO?-N in drinking water in Taiwan. All CBT deaths of Taiwan residents from 1999 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen NO?-N, Ca, and Mg in drinking water were collected from Taiwan Water Supply Corporation. The municipality of residence for CBT cases and controls was presumed to be the source of the subject's NO?-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO?-N exposure level was ≤ 0.31 ppm, and the adjusted odds ration (OR) (95% confidence interval [CI]) for CBT occurrence was 1.4 (1.07-1.84) for individuals who resided in municipalities served by drinking water with a NO?-N exposure > 0.31 ppm. No significant effect modification was observed by Ca and Mg intake via drinking water. Data suggest that exposure to NO?-N in drinking water is associated with a higher risk of CBT development in Taiwan.     

肺癌骨转移105例预后分析

目的探讨肺癌骨转移患者的临床特征及其与预后的关系,筛选影响预后的独立因素。方法对天津市胸科医院2006年1月至2010年12月诊治的105例肺癌骨转移患者的临床特征及预后进行回顾性分析。应用生存曲线法估计全组患者确诊肺癌和确诊骨转移后的生存率;以对数秩检验Log—rank法和考克斯比例风险模型COX法分别进行单因素和多因素分析,筛选影响患者预后的独立因素。结果自确诊肺癌起,患者的中位生存期为19．0个月,1、2年生存率分别为82．9％、29．5％。自确诊骨转移起,患者的中位生存期为10.3个月,1年生存率为38．1％,2年生存率为12．4％。单因素方差分析显示．确诊肺癌时的临床分期、肺癌原发灶手术、确诊骨转移时体力状态（PS）评分、骨转移后的化疗、酪氨酸激酶抑制剂治疗、双磷酸盐治疗与预后相关（P〈0．05）。多因素方差分析显示,确诊肺癌时的临床分期、确诊骨转移时的PS评分、骨转移后的化疗是影响预后的独立因素。结论肺癌骨转移患者的总体预后差,确诊肺癌时临床分期较早、确诊骨转移时PS评分为0～1分、骨转移后接受化疗的患者可能预后相对较好。     

Semen quality of Indian welders occupationally exposed to nickel and chromium

The semen quality of 57 workers from a welding plant in South India and 57 controls was monitored. Blood nickel and chromium concentrations were determined by ICP-MS. Analysis of semen samples was performed in accordance with World Health Organization criteria. The blood level of nickel and chromium for the 28 exposed workers was 123.3 +/- 35.2 and 131.0 +/- 52.6 microg/l, resepctively, which was significantly higher than the 16.7 +/- 5.8 and 17.4 +/- 8.9 microg/l for the control group (n=27). Sperm concentrations of exposed workers were 14.5 +/- 24.0 millions/ml and those of the control group were 62.8 +/- 43.7 millions/ml. Rapid linear sperm motility was decreased in exposed workers compared to controls. There was a significant positive correlation between the percentage of tail defects and blood nickel concentration in exposed workers. The sperm concentration showed a negative correlation with blood chromium content in workers. More abnormal characteristics were found in the semen of exposed workers. Semen abnormalities correlated with the number of years of exposure to welding fumes containing nickel and chromium.     

肺癌组织及以敢管冲洗液中肺癌细胞的端粒酶活性分析

目的研究纤支镜下取得的活检肺癌组织、支气管冲洗液中肺癌细胞的端粒酶活性,探讨其在肺癌诊断中的意义。方法应用银染—TRAP法,检测了26例肺癌组织、4例良性肺疾病组织,相应30例支气管冲洗液中的端粒酶活性表达。结果26例肺癌组织中,22例端粒酶表达阳性,阳性率为84.64%。26例肺癌患者支气管冲洗液中,12例端粒酶表达阳性,阳性率46.15%。结论端粒酶可能成为肺癌早期诊断的重要标志物,可能成为肿瘤治疗方面的重大突破口。     

肺癌组织及支气管冲洗液中肺癌细胞的端粒酶活性分析

目的：研究纤支镜下取得的活检肺癌组织、支气管冲洗液中肺癌细胞的端粒酶活性,探讨并在肺癌诊断中的意义。方法：应用银染－TRAP,检测了26例癌组织、4例良性肺疾病组织,相应30例支气管冲洗液中的端粒酶活性表达。结果：26例肺癌组织中,22例端粒酶表达阳性,阳性率为84．64％。26例肺癌患者支气管冲洗液中,12例端粒酶表达阳性,阳性率46．15％。结论：端粒酶可能成为肺癌早期诊断的重要标志物,可能成为肿瘤治疗方面的重大突破口。     

Immune system alterations in lung cancer patients

The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate. lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00 h from ten healthy subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve, mean diurnal levels (mean of 06.00-10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AUC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8bright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain of IL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the variable domain of d chain of T-cell receptor1) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CD16, TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned.     

Single- and multiple dose pharmacokinetics of lonidamine in patients suffering from non-small-cell lung cancer.

Pharmacokinetic studies of lonidamine (1-[2,4-dichlorobenzyl]- 1H- indazole- 3-carboxylic acid, Doridamina: CAS 50264-69-2) in humans showed a wide variation of the plasma concentration-time profiles following a single peroral dose of 300 mg (Cmax between 6.5 and 40.9 micrograms/ml, tmax between 0.75 and 5.5 h). In order to investigate single and multiple dose pharmacokinetics after peroral administration of this chemotherapeutic compound, a study was performed involving 12 patients with non-small-cell malignancies of the lungs. Plasma and urinary concentration profiles were analyzed for determination of the pharmacokinetic parameters for lonidamine after single dose administration and in the steady state. In addition, age dependency and the presence of liver induction or inhibition was evaluated. Results indicate that steady state was reached after 2 dosing intervals of 12 h and no changes in liver metabolism or age dependent pharmacokinetics could be revealed after 4 days of multiple dose treatment.