1.Expression of the 4-hydroxynonenal in lung tissue in rats with paraquat poisoned and the effect of ulinastatin.
Cong-yan ZHOU ; Shu XIE ; Ya-juan LUO ; Xu-hui TANG ; Fan LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(6):457-459
OBJECTIVETo investigate the 4-hydroxynonenal (4-HNE) expression changes and the impact of ulinastatin (UTI) METHODS: Seventy-two healthy Sprague-Dawley rats were randomly divided into three groups: the control group, poisoning group and treatment group, with 24 rats in each group. The model of lung injury was established by intragastric PQ (80 mg/kg) administration in poisoning group and treatment group, and 1 mL saline was administered intragastrically in the control group. The rats in treatment group were injected intraperitoneally with UTI (100 000 U/kg) 30 minutes after PQ administration, and the rats in the control group and poisoning group were intraperitoneally injected with the same volume of saline. After different treatments, the pathological changes and the expression of 4-HNE in lung tissue was detected in 12, 24, and 72 h in three groups.
RESULTSIn the poisoning group and treatment group, the expression of 4-HNE in lung tissue of rats were increased in 12 h after poisoning and reached the peak in 48 h; in 72 h after poisoning, the expression of 4-HNE in lung tissue were decreased, but they were still high. Compared with the control group, the expression of 4-HNE in lung tissue of rats were significantly increased in the poisoning group and treatment group (P < 0.05). And compared with the poisoning group, the expression of 4-HNE in lung tissue of rats were significantly decreased in the treatment group (P < 0.01). The pathological changes were observed, including alveolar capillary expansion, diffuse alveolar hemorrhage and alveolar inflammation cell infiltration, were found in lungs of rats in poisoning group and treatment group. There is no significant change in the control group. Compared with the control group, the expression of 4-HNE in lung tissue significantly increased in poisoning group and treatment group (P < 0.01), but the expression in treatment group was lower than in poisoning group (P < 0.01).
CONCLUSIONThe expression of 4-HNE increased in PQ intoxicated rats. UTI may reduce the expression of 4-HNE and reduce lung injury in PQ intoxicated rats.
Aldehydes ; metabolism ; Animals ; Glycoproteins ; pharmacology ; Lung ; drug effects ; metabolism ; pathology ; Lung Injury ; metabolism ; pathology ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley
2.Function of type I repetitive consequence peptide segment of thrombospondin-1 in inhibition of fibrosis of mice.
Ying CHEN ; Xing WANG ; Dong WENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2009;27(1):45-47
Animals
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Disease Models, Animal
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Female
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Fibrosis
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metabolism
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pathology
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Hydroxyproline
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metabolism
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Lung
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drug effects
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metabolism
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pathology
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Mice
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Thrombospondin 1
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pharmacology
3.Expression and gene mutation of cluster of differentiation 9 in lung cancer cells induced by mineral powder in Gejiu.
Rui LIANG ; Ke-wei JIN ; Zhi-qiang WANG ; Ji-wu CHANG ; Fu-ling MA ; Yi WANG ; Qian GAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2007;25(9):537-540
OBJECTIVETo investigate the expression and gene mutation of cluster of differentiation 9 (CD9) in the pathway of the mineral powder induced malignant transformation in immortalized human bronchial epithelial cells (BEAS-2B) in Gejiu.
METHODSBEAS-2B cells served as the control group and its malignant transformation cells induced by mineral powder in Gejiu were considered as experiment group. The expression of CD9 protein in 20 bottles of BEAS-2B cells and 20 bottles of malignant transformation cells was evaluated by immunocytochemistry. The mRNA expression of CD9 in 10 bottles of BEAS-2B cells and 10 bottles of malignant transformation cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR). Gene mutation was detected in the products of RT-PCR by DNA sequencing.
RESULTSThere was significant difference between the expression of CD9 protein in BEAS-2B cells (100%, 20/20) and that in its malignant transformation cells (35%, 7/20 P < 0.01). The expression of CD9 mRNA in BEAS-2B cells 0.91 +/- 0.09 was significantly higher than that in its malignant transformation cells (0.34 +/- 0.14) (P < 0.01). Two point mutation of CD9 gene was detected in the malignant transformation cells of BEAS-2B by DNA sequencing. The change of G-->T in the base of 231 led to the change of Gln-->His in the amino acids of 40. The change of T-->A in the base of 119 led to the change of Val-->Asp in the amino acids of 3.
CONCLUSIONThe absence or down-regulation of CD9 expression and point mutation in the malignant transformation cells of BEAS-2B may play a considerable role in the pathway of the malignant transformation in the BEAS-2B cells induced by mineral powder in Gejiu.
Bronchi ; pathology ; Cell Line ; Cell Transformation, Neoplastic ; drug effects ; genetics ; Dust ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Gene Expression Regulation ; drug effects ; Humans ; Lung Neoplasms ; chemically induced ; genetics ; metabolism ; pathology ; Mining ; Mutation ; drug effects ; Tetraspanin-29 ; genetics ; metabolism
4.Observation on the protective effect of hyperoxia solution on the acute lung injury caused by phosgene poisoning..
Ling WANG ; Li-xian XU ; Chun-xu HAI ; Shi-rong TANG ; Xu-ju QIN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(1):20-23
OBJECTIVETo study the protective effect of hyperoxia solution on acute lung injury caused by phosgene poisoning by observing the changes of PaO2 and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity in serum and Glutathione (GSH/GSSG) contents in lung tissues.
METHODSThe rabbits were divided into normal control group, hyperoxia solution (H0) and balance salt (BS) groups. Group HO and Group BS inhaled phosgene and the former was given intravenously hyperoxia solution (which was replaced by balance salt solution in Group BS). The content of MDA and the activity of SOD in serum were observed at different time points, the amount of GSH and GSSG in lung tissue were also measured.
RESULTS(1) The serum MDA contents increased and PaO2, SOD activity decreased significantly in Group HO and Group BS along with time increasing as compared with control group. The contents of GSH in lung tissue decreased in two groups compared with that in control group, however the contents of GSSG ascended instead. (2) At 3 and 8 h of the experiment, PaO2 of Group HO [(9.91 +/- 0.49), (9.15 +/- 0.46) mm Hg respectively] were significantly higher than those of Group BS [(9.03 +/- 0.76), (8.11 +/- 0.57) mm Hg respectively] (P < 0.01). The contents of MDA of Group HO (3.66 +/- 0.35), (5.31 +/- 0.15) micromol/L respectively] were lower than those of Group BS [(4.32 +/- 0.26), (7.4 +/- 0.33) micromol/L respectively] (P < 0.01). SOD activity in Group HO [(237.37 +/- 29.96), (208.10 +/- 18.80) NU/ml respectively] were higher than those of Group BS [(195.02 +/- 21.44), (144.87 +/- 21.26) NU/ml respectively] (P < 0.05 or P < 0.01). The content of GSSG lung tissue in Group HO (423.67 +/- 38.21) micromol/L were lower than those of Group BS (523.85 +/- 43.14) mol/L (P < 0.01). There were no significant differences in the content of GSH in lung tissues between Group HO and group BS.
CONCLUSIONHyperoxia solution can reduce acute lung injury of rabbits following phosgene poisoning.
Acute Lung Injury ; etiology ; metabolism ; pathology ; Animals ; Glutathione Peroxidase ; metabolism ; Hyperoxia ; Lung ; drug effects ; metabolism ; pathology ; Malondialdehyde ; analysis ; Oxygen ; administration & dosage ; pharmacology ; Phosgene ; poisoning ; Rabbits ; Superoxide Dismutase ; metabolism
5.Crystalline Silica Promotes Rat Fibrocyte Differentiation in Vitro, and Fibrocytes Participate in Silicosis in Vivo.
Juan LI ; Wu YAO ; Jian Yong HOU ; Lin ZHANG ; Lei BAO ; Hui Ting CHEN ; Di WANG ; Zhong Zheng YUE ; Yi Ping LI ; Miao ZHANG ; Chang Fu HAO
Biomedical and Environmental Sciences 2017;30(9):649-660
OBJECTIVEThe aim of this study was to investigate the effects of SiO2 on fibrocytes and whether fibrocytes participate in silicosis in vivo.
METHODSA macrophagocyte (AM)/fibrocyte coculture system was established, and AMs were treated with 100 μg/mL SiO2. Flow cytometry was used to detect the number of fibrocytes. Real-time PCR was performed to measure the expression of collagen I, collagen III, and α-SMA mRNA. The levels of collagen I, collagen III, and TGF-β1 protein were determined by ELISA. Immunohistochemical staining was performed to measure α-SMA protein expression. A rat silicosis model was induced by intratracheal instillation of SiO2. Lung histopathological evaluation was conducted using HE and Masson's trichrome staining after 1 and 9 weeks. The number of fibrocytes in peripheral blood or lung tissue of rat was detected by flow cytometry. Double-color immunofluorescence was applied to identify fibrocytes in the lung tissue.
RESULTSPeripheral blood monocytes were found to differentiate into fibrocytes in vitro in a time-dependent manner, and exposure to crystalline silica might potentiate fibrocyte differentiation. In addition, fibrocytes were able to migrate from peripheral blood to the lung tissue, and the number of fibrocytes was increased after SiO2 exposure.
CONCLUSIONSilica exposure potentiates fibrocyte differentiation, and fibrocytes may participate in silicosis in vivo.
Animals ; Cell Differentiation ; drug effects ; Collagen ; metabolism ; Fibroblasts ; drug effects ; Lung ; metabolism ; pathology ; Male ; Rats ; Silicon Dioxide ; toxicity ; Silicosis ; metabolism ; pathology
6.Pirfenidone diminishes SiO2 induced lung fibrosis in rats.
Ling-Fang FENG ; Zhen-Yu JIA ; Li-Jin ZHU ; Li JU ; Jun-Qiang CHEN ; Zhao-Qiang JIANG ; Ri-Ping CHEN ; Zhen MA ; Xing ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(10):772-775
OBJECTIVEto investigate whether pirfenidone (PFD) presents the antifibrotic effect in silicosis of rats.
METHODSSD rats were randomly divided into five groups: the non-treat group, the normal saline group, the normal saline + PFD group, the SiO2 group, the SiO2 + PFD group. Rats except in the non-treat group were intratracheally instilled with SiO2 (25 mg/ml) or normal saline. The rats in normal saline + PFD group and the SiO2 + PFD group were given PFD (50 mg/kg) orally the next day after instillation and throughout the study. Rats were respectively sacrificed 7, 21, 42 days after instillation. The pathology changes were evaluated by Haematoxylin-eosin (HE), Van Gieson and Foot staining, and the hydroxyproline (HYP) content of pulmonary tissue was determined.
RESULTScompared with the SiO2 group, PFD could relieve the fibrotic changes in the lungs of rats. The fibrotic degree in silicotic lesions of lungs was lower in the SiO2 + PFD group than that of SiO2 group. The HYP content in the lungs of the SiO2 + PFD group [(0.75 ± 0.12) mg/g] was significantly lower than that of the SiO2 group [(1.19 ± 0.17) mg/g] at 42 days after instillation (P < 0.05).
CONCLUSIONthese data support that PFD has an antifibrotic effect against SiO2 induced lung fibrosis in rats, Which appears to be changing collagen accumulation and inhibiting pulmonary fibrosis.
Animals ; Hydroxyproline ; metabolism ; Lung ; drug effects ; metabolism ; pathology ; Male ; Pulmonary Fibrosis ; drug therapy ; metabolism ; pathology ; Pyridones ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; adverse effects
7.Puerarin Inhibits the Proliferation,Invasion,and Migration of Non-small Cell Lung Cancer Cells through Regulating miR-490/Denticleless E3 Ubiquitin Protein Ligase.
Yu-Xin ZHANG ; Zhen-Zhen ZHANG ; Li-Gang ZHAO ; Lin-Lin ZHAO
Acta Academiae Medicinae Sinicae 2022;44(1):91-101
Objective To explore the mechanism of puerarin inhibiting the proliferation,invasion,and migration of non-small cell lung cancer cells. Methods A549 cells were cultured and treated with different concentrations of puerarin.The inhibition rate (IR) on cell proliferation was detected by CCK-8,and qRT-PCR was performed to detect the mRNA levels of miR-490 and denticleless E3 ubiquitin protein ligase(DTL).Double luciferase reporter assay was employed to identify the targets of miR-490 and DTL based on the establishment of NC mimic group,miR-490 mimic group,NC inhibitor group,and miR-490 inhibitor group.The cells treated by 20 μmol/L puerarin were classified into six groups:DMSO,puerarin,puerarin+NC inhibitor,puerarin+miR-490 inhibitor,puerarin+miR-490 inhibitor+Si-NC,and puerarin+miR-490 inhibitor+Si-DTL.Transwell was used to detect cell migration and invasion.Western blotting was performed to detect the protein levels of epithelial-mesenchymal transition-related markers E-cadherin,N-cadherin,and Vimentin. Results With the increase in puerarin concentration,the IR gradually elevated (F=105.375,P<0.001),miR-490 expression gradually increased (F=32.919,P<0.001),and DTL expression gradually decreased (F=116.120,P<0.001).Compared with NC mimic group,miR-490 mimic group had decreased luciferase activity (t=7.762,P=0.016),raised miR-490 mRNA level (t=13.319,P<0.001),and declined DTL mRNA level (t=7.415,P=0.002).Compared with those in NC inhibitor group,miR-490 demonstrated decreased mRNA level (t=9.523,P=0.001) and DTL presented increased mRNA level (t=11.305,P<0.001) in miR-490 inhibitor group.Western blotting showed that the protein level of DTL was higher in NC mimic group (t=7.953,P=0.001) than in miR-490 mimic group and higher in miR-490 inhibitor group than in NC inhibitor group (t=10.552,P<0.001).Compared with DMSO group,puerarin group showed up-regulated mRNA level of miR-490 (t=10.255,P=0.001) while down-regulated mRNA level of DTL (t=6.682,P=0.003).Compared with those in puerarin+NC inhibitor group,the mRNA level of miR-490 declined (t=10.995,P<0.001) while that of DTL raised (t=12.478,P<0.001) in puerarin+miR-490 inhibitor group.The mRNA level of miR-490 had no significant difference between puerarin+miR-490 inhibitor+Si-NC group and puerarin+miR-490 inhibitor+Si-DTL group (t=1.081,P=0.341),and that of DTL was lower in the latter group (t=14.321,P<0.001).The protein level of DTL was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=11.423,P<0.001),and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=12.080,P<0.001).Compared with DMSO group,puerarin group showed inhibited cell proliferation (F=129.27,P<0.001).The activity of cell proliferation was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (F=75.12,P<0.001),and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (F=52.59,P<0.001).Compared with DMSO group,puerarin group had suppressed cell migration (t=8.963,P=0.001).The cell migration ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=12.117,P<0.001) and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (t=12.934,P<0.001).Puerarin group showed weakened cell invasion ability compared with DMSO group (t=4.710,P=0.009).The cell invasion ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=13.264,P<0.001) and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=13.476,P<0.001).Compared with DMSO group,puerarin group showed up-regulated protein level of E-cadherin (t=7.137,P=0.002) while down-regulated protein levels of N-cadherin (t=8.828,P=0.001) and vimentin (t=6.594,P=0.003).Compared with those in puerarin+NC inhibitor group,the protein level of E-cadherin (t=12.376,P<0.001) decreased while those of N-cadherin (t=13.436,P<0.001) and vimentin (t=11.467,P<0.001) increased in puerarin+miR-490 inhibitor group.Compared with puerarin+miR-490 inhibitor+Si-NC group,puerarin+miR-490 inhibitor+Si-DTL group up-regulated the protein level of E-cadherin (t=13.081,P<0.001) while down-regulated the protein levels of N-cadherin (t=10.835,P<0.001) and vimentin (t=11.862,P<0.001). Conclusion Puerarin could inhibit the proliferation,invasion,and migration of non-small cell lung cancer cells by up-regulating miR-490 and down-regulating DTL.
Carcinoma, Non-Small-Cell Lung/pathology*
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Cell Line, Tumor
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Cell Movement/drug effects*
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Cell Proliferation/drug effects*
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Humans
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Isoflavones/pharmacology*
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Lung Neoplasms
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MicroRNAs/metabolism*
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Ubiquitin-Protein Ligases/metabolism*
8.The effect of paraquat on voltage-dependent anion channel and caspase-3, 8, 9 in the mitochondria of rat lung.
Dengpan LAI ; Jinming XIA ; Jianfeng WANG ; Xia WEI ; Jin QIAN ; Qiuying LOU ; Xiaohua REN ; Xuefeng HUANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(5):363-365
OBJECTIVETo investigate the effects of different concentrations of paraquat (PQ) poisoning on the expression of voltage-dependent anion channel (VDAC) and caspase family in the mitochondria of rat lung tissue, and to explore possible mechanisms of acute lung injury induced by acute PQ poisoning.
METHODSTwo hundred healthy adult Wister rats with equal numbers of male and female ones were randomly and equally divided into control group and poisoned group. The control group received one-time gastric lavage with 1 ml of normal saline, and the poisoned group with PQ (50 mg/kg) diluted in 1 ml of normal saline. Twenty rats were collected at 1, 24, 72, 120, and 168 h after lavage with normal saline or PQ and dissected after anesthesia. Mitochondria were separated from rat lung tissue, and the content of VDAC and caspase-3, -8, and -9 were determined.
RESULTSThe expression of VDAC and caspase-3, -8, and -9 in the poisoned rats were significantly higher than that in the control group (P < 0.001). At 1, 24, 72, 120, and 168 h after exposure, acute diffuse damages were found in alveolar capillary endothelial cells, alveolar epithelial cells, and pulmonary interstitial cells. Inflammatory cell infiltration in the pulmonary interstitium, alveolar structural disorder, and substantially increased fibroblasts were also found in rat lung tissue.
CONCLUSIONPQ poisoning can up-regulate the expression of VDAC and caspase-3, -8, and -9 in mitochondria of rat lung tissue to induce acute lung injury.
Acute Lung Injury ; chemically induced ; pathology ; Animals ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Caspases ; metabolism ; Female ; Lung ; drug effects ; pathology ; Male ; Mitochondria ; drug effects ; metabolism ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley ; Voltage-Dependent Anion Channels ; metabolism
9.Protective effect of melatonin on reexpansion pulmonary edema in rats model.
Ming ZHONG ; Zhang-gang XUE ; Jing CANG ; Wei WU ; Jun-feng HUANG ; Du-ming ZHU
Chinese Medical Journal 2013;126(3):500-504
BACKGROUNDRapid reexpansion of collapsed lungs leads to reexpansion pulmonary edema (RPE). We aimed to investigate the effect of melatonin in the prevention of RPE formation.
METHODSWe used a Wistar rat model in which the left lung was collapsed by ligating the left bronchus for 48 hours and then reexpanded and ventilated for an additional 2 hours. Thirty minutes before reexpansion, we injected melatonin (10 mg/kg) or vehicle intraperitoneally. We compared the wet/dry ratio, oxygenation index, myeloperoxidase (MPO) activity, nitric oxide (NO), malondialdehyde (MDA) and interleukin 8 (IL-8) levels in the reexpanded lungs between untreated and treated animals.
RESULTSWe found that the wet/dry ratio of the melatonin group was significantly lower than that of the vehicle group, and the oxygenation index was higher in the melatonin group. Compared with the control, melatonin pretreatment significantly decreased the activities of IL-8, NO, MDA levels and MPO in lung tissues. Histopathology of reexpanded lungs showed that the melatonin pretreatment group had less pulmonary edema and less inflammatory cell infiltration.
CONCLUSIONMelatonin decreases pulmonary edema and improves oxygenation after reexpansion by attenuating oxidative stress and inhibiting pro-inflammatory cytokines.
Animals ; Cytokines ; metabolism ; Interleukin-8 ; metabolism ; Lung ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Melatonin ; therapeutic use ; Nitric Oxide ; metabolism ; Oxidative Stress ; drug effects ; Peroxidase ; metabolism ; Pulmonary Edema ; drug therapy ; metabolism ; pathology ; Rats ; Rats, Wistar
10.Research Advances of Ang-2 in Non-small Cell Lung Cancer.
Chinese Journal of Lung Cancer 2018;21(11):868-874
Non-small cell lung cancer (NSCLC) is one of the malignant tumors with highest mortality in the world, it is still a difficult problem in clinical field. Its occurrence and development are closely associated with tumor angiogenesis. Angiopoietin-2 (Ang-2) is an important angiogenesis factor that has involved in many researches and it has been confirmed that the expression of Ang-2 is significantly up-regulated in tissues and blood of NSCLC. Meanwhile, Ang-2 is related to malignant biological behavior of cancer cells, making it a potential biological marker for the diagnosis and prognosis of NSCLC. At present, researches on Ang-2 how to promote the progression of NSCLC around the world are focused on Ang-2 regulating the proliferation, invasion, and metastasis of NSCLC. This paper summarized and estimated the studies and literature reports of regulatory mechanisms of Ang-2 in NSCLC, hopefully it could help looking for targeted drug treatment of Ang-2 in the future.
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Angiopoietin-2
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genetics
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metabolism
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Carcinoma, Non-Small-Cell Lung
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drug therapy
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genetics
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metabolism
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pathology
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Gene Expression Regulation, Neoplastic
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drug effects
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Humans
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Lung Neoplasms
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drug therapy
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genetics
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metabolism
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pathology
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Molecular Targeted Therapy
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Signal Transduction
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drug effects