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Serum and Lung Tissue Selenium Measurements in Subjects with Lung Cancer from Xuanwei, China
Lan ZHOU,Yunchao HUANG,Zhu WANG,Lianhua YE
Chinese Journal of Lung Cancer , 2011,
Abstract: Background and objective Xuanwei is an area of the highest incidence and mortality with lung cancer in China. The aim of this study is to determine serum selenium concentrations in lung cancer patients from Xuanwei as well as selenium levels of cancerous tissues, cancer-adjacent pulmonary tissues, and normal pulmonary lung tissues from lung cancer patients, and the relationship between selenium and the high incidence of lung cancer in Xuanwei. Methods One hundred and twenty female adults from Xuanwei were enrolled in the study (60 lung cancer patients and 60 with non-tumor and non-respiratory diseases, respectively) and blood samples were collected. Sixty fresh cancerous tissues and their adjacent as well as normal tissues were collected (31 samples from lung cancer patients living in Xuanwei for more than 2 years and 29 from patients in other regions of Yunnan Province outside of Xuanwei, respectively). Serum and tissue selenium concentrations were assayed using a fluorometric method. Results Women with lung cancer had a mean serum selenium value (55.22 μg/L±13.34 μg/L) of averagely 8.47%, significantly lower than that in subjects with non-tumor and non-respiratory disease controls (60.33 μg/L±13.82 μg/L)(P < 0.05). Selenium concentrations in the tumor tissues (0.105 μg/g±0.034 μg/g) were statistically lower than that of normal ones (0.140 μg/g±0.048 μg/g)(P < 0.05) from lung cancer patients in Xuanwei. Statistical differences had not been found between the cases from Xuanwei and non-Xuanwei district, adenocarcinoma and squamous cell carcinoma, among Stage I, Stage II, stage III groups. Conclusion Lower serum selenium state was negatively related to the incidence of lung cancer in Xuanwei. It was likely that lower selenium level of lung tissues was potential risk factor to lead to lung cancer.
Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients
Jiapeng YANG, Guangjian LI, Yunchao HUANG, Lianhua YE, Yongchun ZHOU, Guangqiang ZHAO, Yujie LEI, Xiaobo CHEN, Kun WANG, Ying CHEN, Chun DAI, Yanjun ZHANG
- , 2016, DOI: : 10.3779/j.issn.1009-3419.2016.01.04
Abstract: Background and objective Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients. Methods From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. Results A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50±19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33±6.94) pg/mL (P<0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124±8.597) ng/mgCr were significantly higher than those of patients from other regions (25.673±7.986) ng/mg Cr (P<0.05), with statistically significant difference. Conclusion The accumulation of inorganics and the activation of NF-κB-iNOS signaling pathway may contribute to Xuanwei lung cancer.
Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model and Analysis of Biological Properties
Yongchun ZHOU,Yan CHEN,Xicai WANG,Xin LIU
Chinese Journal of Lung Cancer , 2012, DOI: 10.3779/j.issn.1009-3419.2012.08.01
Abstract: Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID) mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05). A significant difference was indicated by the survival rate within and between the groups (P<0.001). Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.
Study on the Relationship between the Inhalable Fine Particulate Matter of Xuanwei Coal Combustion and Lung Cancer
Jiapeng YANG, Yu CAO, Yunchao HUANG, Guangjian LI, Lianhua YE, Guangqiang ZHAO, Yujie LEI, Xiaobo CHEN, Linwei TIAN
- , 2015, DOI: : 10.3779/j.issn.1009-3419.2015.07.03
Abstract: Background and objective The high incidence of lung cancer in Xuanwei, China, has become an important restricting factor for livelihood development, thus exerting local social and economic impacts. Coal is the main fuel of the local community and also the main source of indoor pollution. This study aims to explore the coal combustion inhalable fine particulate matter (PM2.5) and its component output differences in different areas of Xuanwei, Yunnan. Moreover, the aim of this study is to investigate the relationship between inhalation of fine particles and high incidence of local lung cancer. Methods For combustion test, coal mines designated as C1, K7 and M30 were collected from LaoLin Colliery of Laibing Town, Huchang Colliery of Baoshan Town, and Taiping Colliery of Wenxing Town in Xuanwei, respectively. PM2.5 of indoor air was weighed, analyzed for elemental composition, and morphologically compared. The pathological specimen of lung cancer patients in Xuanwei who underwent operation was observed through electron microscope. Results The PM2.5 concentrations in indoor air were (8.244 ±1.460) mg/m3 (C1), (5.066±0.984) mg/m3 (K7), and (5.071±1.460) mg/m3 (M30). The differences among pairwise comparisons were statistically significant (P=0.029). The filter impurities of C1 coal seam primarily include Si- and O-enriched compounds. Moreover, three membranes that comprised other elements, including C, S, and Si, were observed. These membranes were evident from the aggregation of silica and a Ca-Al membrane. Compared with that of other coal seams, C1 coal generated a mass of impurities, in which several particles have irregular shape. We found nanoscale fine particles in some specimens of Xuanwei lung cancer patients. Conclusion The produced combustion of C1 coal was different from that of K7 and M30 coal. PM2.5 composition may be associated with the high local incidence of lung cancer.
Expression and Clinical Significance of the Thyroid Transcription Factor 1 in Xuanwei Lung Adenocarcinoma
Yunfen ZU,Xicai WANG,Xin LIU,Yan CHEN
Chinese Journal of Lung Cancer , 2013, DOI: 10.3779/j.issn.1009-3419.2013.03.03
Abstract: Background and objective The present study aims to detect the expressions of the thyroid transcription factor 1 (TTF-1) mRNA and protein in Xuanwei lung adenocarcinoma line (XWLC-05). We also investigated the relationship of TTF-1 with Ki-67 protein and analyzed the prognostic value of the TTF-1 protein in Xuanwei lung adenocarcinoma patients. Methods The expression of TTF-1 mRNA was evaluated by quantitative real-time RT-PCR (qRT-PCR), while proteins of TTF-1 and Ki-67 were detected by immunohistochemistry in XWLC-05. The expressions of TTF-1 and Ki-67 was detected in 96 resected cases of Xuanwei lung adenocarcinoma by immunohistochemistry from January 2008 to March 2012. Results TTF-1 mRNA was low and protein was absent in XWLC-05. The expression of Ki67 protein was 100% (high proliferative activity) in XWLC-05. All samples were Xuanwei lung adenocarcinoma (n=96) and TNM stages were I-II 66% (63/96) and III 34% (33/96). Immunohistochemical analysis showed the expression of TTF-1 in 89 (93%) of 96 and Ki-67 in 69 (70%) of 96. The positive rate of TTF-1 protein was 38 (96%) of 39 in well-differentiated phenotype and 51 (89%) 57 in moderately/poorly-differentiated phenotype. Patients with strong immunohistochemical expression of TTF-1 were statistically associated with well-differentiated phenotype (P=0.002), has inverse correlation with Ki-67 expression (P=0.01), and no correlation with age, sex, smoking history, and stages. The result from the Kaplan-Meier survival analysis showed that stages TTF-1 and Ki-67 were significantly associated with the prognosis of Xuanwei lung adenocarcinoma patients. The median progression-free survival in patients with I-II stages, strong positive expression TTF-1 and negative, and weak expressions Ki-67 groups was remarkably higher than those patients with III stage (46 months vs 32 months, P=0.001), negative and weak expressions TTF-1 (45 months vs 35 months, P=0.036) and strong positive expression Ki-67 groups (46 months vs 40 months, P=0.048), respectively. Conclusion Our results presented here suggest that TTF-1 may serve as a tumor suppressor gene based on its inverse correlation with Ki-67 proliferative activity. Patients with strong TTF-1 protein expression group tend to have a significantly better prognosis than patients with negative and weak TTF-1 protein expression group in Xuanwei lung adenocarcinoma.
Expression of PAH-DNA Adducts in Lung Tissues of Xuanwei Female Lung Cancer Patients
Kaiyun YANG,Yunchao HUANG,Guangqiang ZHAO,Yujie LEI
Chinese Journal of Lung Cancer , 2010,
Abstract: Background and objective The coal-fired pollution in Xuanwei area has been considered to be local main reason for high incidence of female lung cancer. The aim of this study is to explore the expression of PAH-DNA adducts in lung tissues of Xuanwei female lung cancer patients and to explore the relationship between the large number of coal-fired pollution PAHs materials and the high incidence of Xuanwei female lung cancer. Methods We totally collected each 20 cases of Xuanwei female lung cancer patients, Xuanwei male lung cancer patients, Non-Xuanwei female lung cancer patients and collect each 10 cases of Xuanwei, Non-Xuanwei female patients with benign lung lesions. The cancer tissues, adjacent cancer tissues and normal lung tissues were collected in lung cancer patients and only the normal tissues were collected in benign lung lesion patients. There were total 80 cases and 200 tissues. Immunofluorescence was used to detect the expression of PAHDNA adducts in each group. Image pro-plus 6.0 software was used to analyze the images and part quantified analysis. SPSS 13.0 statistical software was used to analyze the data. Results The positive expression of PAH-DNA adducts in lung cancer tissues, adjacent cancer tissues and normal lung tissues of Xuanwei female lung cancer patients were 90%, 80% and 65%. They were higher than the positive expression of PAH-DNA adducts in Xuanwei male lung cancer patients (35%, 30%, 30%) and Non-Xuanwei female lung cancer patients (20%, 15%, 10%)(P < 0.01). The expressions in lung tissues of Xuanwei female benign lung lesion patients (positive expression is 70%) were higher than it in Non-Xuanwei female benign lung lesion patients (positive expression is 10%). With the direction changing from cancer tissues, adjacent cancer tissues to normal lung tissues, the expressions of PAH-DNA adducts were decreased but had no statistical difference (P>0.05). Conclusion The expressions of PAHDNA adducts in lung tissues of Xuanwei female were higher than which in Xuanwei male and Non-Xuanwei female.
Study of the Changes on Tree Shrew Bronchial Epithelium ?Induced by Xuanwei Bituminous Coal Dust
Xiaobo CHEN, Meng HE, Guangjian LI, Yongchun ZHOU, Guangqiang ZHAO, Yujie LEI, Kaiyun YANG, Linwei TIAN, Yunchao HUANG
- , 2015, DOI: : 10.3779/j.issn.1009-3419.2015.08.01
Abstract: Background and objective Lung cancer is the type of cancer with the highest incidence and mortality in numerous countries and regions. Establishing an appropriate animal model that can be used to simulate lung cancer etiology, pathogenesis, and similar processes, is urgent. We explore the feasibility of establishing a lung cancer model induced by Xuanwei bituminous coal dust PM10 (particulate matter with diameters of 10 μm or less), which affects bronchial epithelium of tree shrews. Methods The neck skin of adult tree shrews is dissected, and the thyroid cartilage is fully exposed. Subsequently, the weak part at the top of the thyroid cartilage is treated with intratracheal agents by perfusion via a special infusion needle puncture method. Regular X-ray examination and lung tissue biopsy were performed on the sacrificed animals to observe changes in pulmonary imaging and bronchial epithelial cells after perfusion of Xuanwei bituminous coal dust PM 10. Results The tree shrews of the experimental group (exposed to bituminous coal dust) died in a week after perfusion with PM10, whereas no animal died until the end of the experiment in the blank control and the solvent control groups. Sections of lung tissue biopsy of the regularly killed tree shrews were stained with hematoxylin and eosin. The lung tissues of tree shrews in the experimental group showed a serial changes caused by bronchial epithelial hyperplasia, such as squamous metaplasia, dysplasia, and early invasive carcinoma, whereas no significant pathological changes were observed in the blank control and solvent control groups. Conclusion Endotracheal infusion of Xuanwei bituminous coal dust PM10 induces lung cancer in tree shrews. Thus, the lung cancer model was established.
Risk Factors of Lung Cancer in Xuanwei, Yunnan Province, China
Liqun LIU, Xia WAN, Gongbo CHEN, Xiangyun MA, Bofu NING, Gonghuan YANG
- , 2017, DOI: : 10.3779/j.issn.1009-3419.2017.08.05
Abstract: Background and objective Since 1970s, Xuanwei in Yunnan province has been one of the towns with highest lung cancer mortality in China. Moreover, the characters of high female lung cancer mortality and sub-regional clustering high lung cancer mortality have not changed. In this study, we further described the exposure situation of risk factors of lung cancer in Xuanwei nowadays, in order to explore the trend of the distribution of lung cancer there. Methods Firstly we divided the 26 towns of Xuanwei city to high-, median- and low- lung cancer areas by the lung cancer mortality in 2010-2012. We chose 2 towns within each area according to topography and orientation, and randomly picked 4 villages in each town to be our study area. We did a questionnaire about lung cancer related risk factors upon the sample population in the study area. We calculated the exposure percentages of each risk factor, in whole sample population and subgroups, for nowadays and for 10 years ago (only living environmental risk factors), and compared them between areas or time points using standardized rates and the statistical test of standardized rate comparison, or chi-square test. Results 65%-80% male in the study area has a history of smoking; 60%-90% non-smoker has been exposed to second hand smoke. These situations are worse in high and median lung cancer areas. 50% male in median lung cancer area have coal mining work experience, which is 2 times of the percentages in the other two areas; while 15%-25% people in high lung cancer area have other occupational exposure history to particulate air pollution, which is 3-5 times of the percentages in the other two areas. From ten years ago until nowadays, 80% families in median lung cancer area use 2 tons or more smoky coal per year; more than 90% families burn coal for household heating; more than 60% families suffer from smog in the kitchen during cook; 60% families most frequently use stove in the ground with chimney. Only 20% families in high lung cancer area now use 2 tons or more smoky coal per year. Now 50%-75% families in the study area use 700 kilowatt-hours of electricity per year, much more than ten years ago. 80% residents in low lung cancer area eat fatty or pickled or smoked food at least 3 days per week; while in high and median lung cancer areas the percentages are 50%-60%. Conclusion According to data obtained in this survey, current distribution of smoky coal use has differed from the distribution of high-, median- and low- lung cancer areas. Tobacco use and second hand smoke, the use of smoky coal and
- , 2018, DOI: 10.13982/j.mfst.1673-9078.2018.8.009
Abstract: 采用双向凝胶电泳技术结合基质辅助激光解析电离-串联飞行时间质谱,研究了以宣威杂交猪后腿按传统工艺加工的宣威火腿在腌制前(24 h)、腌制结束(18 d)、风干结束(125 d)、成熟中期(250 d)、成熟结束(360 d)等5个阶段的股二头肌的蛋白质降解规律。也分析了组织蛋白酶在宣威火腿加工过程中的活性变化规律。研究显示,宣威火腿在各个阶段的蛋白质斑点数分别为1533、1523、1402、1196与1018个,而组织蛋白酶B和L的潜在活力在火腿加工结束时的残余活力分别为腌制前的10.25%和8.56%。可见,肌肉蛋白质在宣威火腿加工过程中存在明显的降解情况,其中成熟中期到成熟结束阶段的蛋白降解更为突出,而组织蛋白酶B和L的潜在活力在加工过程中均逐渐下降。
The protein hydrolysis of egged biceps femoris of Xuanwei ham, produced from 30 green hams by the traditional processing techninology, during five periods of processing (24 h, 18 d, 125 d, 250 d, 360 d), was characterized using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight-time of flight-mass spectrometry (MALDI-TOF/TOF MS). The cathepsin activity was also monitored during the processing. The results indicated that, the mature protein spots of Xuanwei ham during 5 stage were 1533, 1523, 1402, 1196 and 1018, respectively, and the residual activity of cathepsin B and L in ham processing was 10.25% and 8.56%, respectively. The hydrolysis of muscle protein distinctly occurred during the processing of Xuanwei ham, which was more distinct at the stage from 250 to 360 days. The activity of cathepsin B and L decreased gradually during processing.
Molecular Epidemiology Study in Xuanwei: the Relationship among?Coal Type, Genotype and Lung Cancer Risk
Jihua LI, Jun HE, Rui TANG, Wei HU, Qing LAN, Xingzhou HE, Yun LI, Yunsheng ZHANG
- , 2015, DOI: : 10.3779/j.issn.1009-3419.2015.01.03
Abstract: Background and objective It has been proven that the lung cancer mortality rate in Xuanwei County, China was among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in genetic polymorphisms and coal subtypes. Our objective was to use molecular epidemiological techniques to investigate the relationship among genetic polymorphisms, coal subtype and lung cancer risk in Xuanwei County. Methods On the basis of two population-based case-control studies in residents of Xuanwei County, China, questionnaires covering demographic information, smoking history, family and personal medical history, and information on other variables were administered and buccal cells and sputum samples were collected separately from each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1 superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs were used to estimate the association between genotypes, coal subtypes and lung cancer risk factors by conditional Logistic regression using Statistical Analysis Software. Results Compared with subjects who using smokeless coal or wood, smoky coal use was statistically significantly associated with lung cancer risk (OR=7.7, 95%CI: 4.5-13.3). There was marked heterogeneity in risk estimates for specific subtypes of smoky coal. Estimates were highest for coal from the Laibin (OR=24.8), Longtan (OR=11.6) and Baoshan (OR=6.0) coal types, and lower for coal from other types; the risk within the same subtype of coal in male and female were similar. The GSTM1-null genotype, the AKR1C3 (Ex1-70C>G), OGG1 (Ex6-315C>G) genotypes were closely associated with increased risk of lung cancer in Xuanwei County, and their odds ratios (95%CI) were 2.3 (1.3-4.2), 1.8 (1.0-3.5) and 1.9 (1.1-3.3), respectively. Compared to subjects who with GSTM1-positive and used less than 130 tons of smoky coal during their lifetime, higher risks were closely associated with GSTM1-null and heavier users (≥130 tons), with the OR was 4.9 (95%CI: 1.3-18.2) and 2.7 (95%CI: 1.0-7.4) for female and male, respectively. However, higher risks were only found within female for AKR1C3 (Ex1-70C>G) and OGG1 (Ex6-315C>G), with OR (95%CI)=12.9 (2.2-107.8) and 5.7 (1.1-34.2), respectively. Conclusion Lung cancer risks varied among coal subtypes; however, risks were similar between men and women exposed to the same type of coal. The GSTM1-null genotype may enhance susceptibility to air
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