Manganese-containing superoxide dismutase (Mn-SOD) activity in lung cancer tissues from 5 patients with pulmonary carcinoma were measured by the nitrite formation method, lipid peroxide (LPO) values being measured by ...Manganese-containing superoxide dismutase (Mn-SOD) activity in lung cancer tissues from 5 patients with pulmonary carcinoma were measured by the nitrite formation method, lipid peroxide (LPO) values being measured by spectrophotometry of thio-barbituric acid reaction. The results obtained show that Mn-SOD activity exhibits most evidently in lung cancer tissues, less evidently in peripheral tissues around the lung cancer, but the least in normal peripheral lung tissues, indicating a declined tendency as definitely proved by statistical treatment (P<0.01). In addition, LPO values are found to be lower in lung cancer tissues than those in normal peripheral tissues.展开更多
Objective: To investigate the effect of paclitaxel on cell proliferation and apoptosis of human lung adenocarcinoma A549 cells line and its mechanism in vitro. Methods : Cell growth inhibition of paclitaxel on A549 ...Objective: To investigate the effect of paclitaxel on cell proliferation and apoptosis of human lung adenocarcinoma A549 cells line and its mechanism in vitro. Methods : Cell growth inhibition of paclitaxel on A549 cells was analyzed by MTT assay. Cell apoptosis was detected by DNA cytofluorometry, Hoechst33258 staining when treated with paclitaxel for 48 hours. Meanwhile, Cell cycle and apoptotic rate were analyzed by flow cytometry. The protein expressions of Bax and Bcl-2 were studied by Western Blot. Results: Paclitaxel inhibited the proliferation of A549 cells in a time-and dose-dependant manner. Hoechst33258 staining indicated that apoptosis was induced by paclitaxel. After treated for 48 hours, cell apoptosis rates of 25 nmo1/L, 50 nmol/L and 100 nmol/L paclitaxel groups were 11.52 ± 1.94% ,17.73 ±2.53%, and 29.32 ±5.51% respectively, which were significantly higher than those of control group 5.88 ±1.07%(all P 〈 0.01 ), and apoptosis rate increased in dose-dependant manner. Meanwhile, G2/M stage cell percentage of 25 nmol/L, 50 nmol/L and 100 nmol/L paclitaxel groups were 42.52 ± 6.25%, 40.46 ± 5.81%, and 35.34 ±6.17% respectively,which were significantly higher than that of control group 22.32 ± 3.30%(all P 〈 0.01 ); Western blot showed that paclitaxel increased the expression of Bax and decreased the expression of Bcl-2 in dose-dependant manner. Conclusion: Paclitaxel can inhibit A549 cell proliferation in a time-and dose-dependant manner. Its mechanism may be related to arresting cell cycle in G2/M stage and induce cell apoptosis by up-modulating Bax expression and down-modulating Bcl-2 expression.展开更多
A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained i...A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.展开更多
By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of ...By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.展开更多
Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological pro...Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.展开更多
Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),...Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),PPARγ has been studied the most,in part because of the availability of PPARγagonists(also known as PPARγ ligands)and its significant effects on the management of several human diseases including type 2 diabetes,metabolic syndrome,cardiovascular disease and cancers.PPARγ is expressed in many tumors including lung cancer,and its function has been linked to the process of lung cancer development, progression and metastasis.Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands.Furthermore,data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer.This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.展开更多
The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of t...The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.展开更多
Objective and Methods Lung cancer has a fastest growing rate of morbidity and mortality among malignant tumors and poses a great threat to the human health. Chemotherapy, as one
Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by
The human lung cancer has high incidence rate and mortality among the carcinoma. The research on enhancing the efficacy of therapy for lung cancer is significant. A resent research found that as a subunit of ESCRT-III...The human lung cancer has high incidence rate and mortality among the carcinoma. The research on enhancing the efficacy of therapy for lung cancer is significant. A resent research found that as a subunit of ESCRT-III, CHMP4C functioned to retard abscission timing to coordinate midbody resolution and prevent accumulation of DNA damage in the abscission checkpoint through phosphorylated by AuroraB. In the current study, we evaluated the possible mechanism of the effects of CHMP4C inhibition on cell cycle and cell survival in A549 cells. We found that CHMP4C knockdown caused lagging S phase in cell cycle through enhancing the phosphorylation of Rb, raising the expression of cyclin B1-cdc2 and suppressing the activation of cyclin A. Meanwhile, CHMP4Cdeletion depressed cell survival via decreasing cell viability and increasing caspase 3/7 activity. This study may promote new significant reference and advance for the mechanism underlying specific function of CHMP4C as well as further research on enhancing therapy effect on non-small lung cancer.展开更多
The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed...The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [3H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β2-AR.展开更多
Leu 7(HNK-1),a glycoprotein,is a specific antigen presented on the surfaceof human natural killer cells and killer cells.In this study ABC immunostaining with spe-cific monoclonal antibody to Leu 7 was used to detect ...Leu 7(HNK-1),a glycoprotein,is a specific antigen presented on the surfaceof human natural killer cells and killer cells.In this study ABC immunostaining with spe-cific monoclonal antibody to Leu 7 was used to detect the expression of Leu 7 in humanlung.The results demonstrated that the Leu 7 immunoreactivity was localized in theneuroepithelial bodies(NEB)and neuroendocrine cells(NEC)of the human lung.In addi-tion,the anti-Leu 7 monoclonal antibody stained the nerve fibers in the wall of theintrapulmonary bronchi.Adjacent sections immunostained with antibodies to Leu 7 and5-hydroxytryptamin(5-HT)or calcitonin gene-related peptide(CGRP)proved thecoexistence of Leu 7 and CGRP or 5-HT in endocrine cells.The CGRP immunoreactivenerve fibers also showed positive staining with the monoclonal antibody to Leu 7.Ourfindings support the hypothesis that the nervous and endocrine systems share some com-mon antigenic determinants with the immune system.展开更多
The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Fin...The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Finite difference method is incorporated to simulate the problem. The numerical results are compared with square duct channel for different parametric effect. It is observed that the flow rate is increased in cylindrical channel compared to square duct channel for the increasing value of pressure gradient, porosity and permeability. On the contrary, the flow rate is decreased in square duct channel compared to cylindrical channel for increasing value of viscosity. Flow rate in both channels is analyzed and compared for non-porous medium also. It is observed that flow rate is increased very high in cylindrical channel compared to square duct channel for both medium.展开更多
Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work conce...Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work concerns the functional expression of gap junction protein connexin 43 (Cx43) in normal human lung cells and the changes in lung carcinoma cells. By. using Northern blot hybridization analysis and Cx43 immunocytochemical methods, it was otherved that cultured normal human embryonic lung cells expressed a high level of Cx43 in both mRNA and protein levels.The Cx43 immunofluorescence was localized at cell membrane regions corresponding to the location of gap junctions. These normal lung cells were competent of intercellular communication function as detected by Lucifer yellow dye transfer. In contrast to normal celis, Cx43 mRNA and protein was not detectable in the carcinoma PG cell line. These tumor cells were defective of intercellular communication function. These results demonstrate that Cx43 is expressed in normal cultured human embryonic lung cells but not in lung tumor cells. The lack of intercellular communication in the lung tumor cell line correlates with dysfunctional intercellular communication. The suggestive role of Cx as a tumor suppersor gene is discussed.展开更多
Background Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effect...Background Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug.Methods Survivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin)cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM).The protein expression levels of survivin, LRP, cyclin-D1, caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo.Results Survivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug-resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth.Conclusions Survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3.Anti-tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas.展开更多
Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-d...Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorp-tion/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load. The average deviation of spot position was 0.733±0.101 mm in IEF direction, and 0.925±0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190±72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls. Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduc-tion. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis. These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.展开更多
Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control th...Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control the growth of tumor cells, ODC antisense RNA was used to transfect human lung squamous carcinoma cell line LTEP-78. Compared with the parental cells, growth of the antisense transfected LTEP-78 cells arrested in G0/Gl phase and colony formation in soft agarose and tumorigenicity in nude mice were significantly reduced. Nucleic acid hybridization demonstrated that the transfectants expressed a high level of ODC antisense RNA and a significantly reduced level of endogenous ODC mRNA.The results suggest that the reversion of malignant phenotypes of human lung squamous carcinoma cells transfected with ODC antisense RNA is associated with the inhibition of polyamine biosynthesis.展开更多
文摘Manganese-containing superoxide dismutase (Mn-SOD) activity in lung cancer tissues from 5 patients with pulmonary carcinoma were measured by the nitrite formation method, lipid peroxide (LPO) values being measured by spectrophotometry of thio-barbituric acid reaction. The results obtained show that Mn-SOD activity exhibits most evidently in lung cancer tissues, less evidently in peripheral tissues around the lung cancer, but the least in normal peripheral lung tissues, indicating a declined tendency as definitely proved by statistical treatment (P<0.01). In addition, LPO values are found to be lower in lung cancer tissues than those in normal peripheral tissues.
文摘Objective: To investigate the effect of paclitaxel on cell proliferation and apoptosis of human lung adenocarcinoma A549 cells line and its mechanism in vitro. Methods : Cell growth inhibition of paclitaxel on A549 cells was analyzed by MTT assay. Cell apoptosis was detected by DNA cytofluorometry, Hoechst33258 staining when treated with paclitaxel for 48 hours. Meanwhile, Cell cycle and apoptotic rate were analyzed by flow cytometry. The protein expressions of Bax and Bcl-2 were studied by Western Blot. Results: Paclitaxel inhibited the proliferation of A549 cells in a time-and dose-dependant manner. Hoechst33258 staining indicated that apoptosis was induced by paclitaxel. After treated for 48 hours, cell apoptosis rates of 25 nmo1/L, 50 nmol/L and 100 nmol/L paclitaxel groups were 11.52 ± 1.94% ,17.73 ±2.53%, and 29.32 ±5.51% respectively, which were significantly higher than those of control group 5.88 ±1.07%(all P 〈 0.01 ), and apoptosis rate increased in dose-dependant manner. Meanwhile, G2/M stage cell percentage of 25 nmol/L, 50 nmol/L and 100 nmol/L paclitaxel groups were 42.52 ± 6.25%, 40.46 ± 5.81%, and 35.34 ±6.17% respectively,which were significantly higher than that of control group 22.32 ± 3.30%(all P 〈 0.01 ); Western blot showed that paclitaxel increased the expression of Bax and decreased the expression of Bcl-2 in dose-dependant manner. Conclusion: Paclitaxel can inhibit A549 cell proliferation in a time-and dose-dependant manner. Its mechanism may be related to arresting cell cycle in G2/M stage and induce cell apoptosis by up-modulating Bax expression and down-modulating Bcl-2 expression.
文摘A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.
文摘By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.
基金supported by the National Natural Science Foundation of China(No.314 008 55)the Technological Innovation Incubator Program from Henan University of Technology(No.201 518)the Introduced Postdoctoral Talents of Henan University of Technology(No.150 199)
文摘Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.
基金Supported by The National Institutes of Health CA123104(HanSW) and CA116812(Roman J)
文摘Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),PPARγ has been studied the most,in part because of the availability of PPARγagonists(also known as PPARγ ligands)and its significant effects on the management of several human diseases including type 2 diabetes,metabolic syndrome,cardiovascular disease and cancers.PPARγ is expressed in many tumors including lung cancer,and its function has been linked to the process of lung cancer development, progression and metastasis.Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands.Furthermore,data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer.This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.
文摘The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.
基金supported by the grants from the Key Project of National Natural Science Foundation of China (No.30430300 , to Qinghua ZHOU)Key Projects of Tianjin Sci-Tech Support Program (No. 07SYSYSF05000 and No. 06YF-SZSF05300, to Qinghua ZHOU)
文摘Objective and Methods Lung cancer has a fastest growing rate of morbidity and mortality among malignant tumors and poses a great threat to the human health. Chemotherapy, as one
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by
文摘The human lung cancer has high incidence rate and mortality among the carcinoma. The research on enhancing the efficacy of therapy for lung cancer is significant. A resent research found that as a subunit of ESCRT-III, CHMP4C functioned to retard abscission timing to coordinate midbody resolution and prevent accumulation of DNA damage in the abscission checkpoint through phosphorylated by AuroraB. In the current study, we evaluated the possible mechanism of the effects of CHMP4C inhibition on cell cycle and cell survival in A549 cells. We found that CHMP4C knockdown caused lagging S phase in cell cycle through enhancing the phosphorylation of Rb, raising the expression of cyclin B1-cdc2 and suppressing the activation of cyclin A. Meanwhile, CHMP4Cdeletion depressed cell survival via decreasing cell viability and increasing caspase 3/7 activity. This study may promote new significant reference and advance for the mechanism underlying specific function of CHMP4C as well as further research on enhancing therapy effect on non-small lung cancer.
文摘The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [3H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β2-AR.
文摘Leu 7(HNK-1),a glycoprotein,is a specific antigen presented on the surfaceof human natural killer cells and killer cells.In this study ABC immunostaining with spe-cific monoclonal antibody to Leu 7 was used to detect the expression of Leu 7 in humanlung.The results demonstrated that the Leu 7 immunoreactivity was localized in theneuroepithelial bodies(NEB)and neuroendocrine cells(NEC)of the human lung.In addi-tion,the anti-Leu 7 monoclonal antibody stained the nerve fibers in the wall of theintrapulmonary bronchi.Adjacent sections immunostained with antibodies to Leu 7 and5-hydroxytryptamin(5-HT)or calcitonin gene-related peptide(CGRP)proved thecoexistence of Leu 7 and CGRP or 5-HT in endocrine cells.The CGRP immunoreactivenerve fibers also showed positive staining with the monoclonal antibody to Leu 7.Ourfindings support the hypothesis that the nervous and endocrine systems share some com-mon antigenic determinants with the immune system.
文摘The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Finite difference method is incorporated to simulate the problem. The numerical results are compared with square duct channel for different parametric effect. It is observed that the flow rate is increased in cylindrical channel compared to square duct channel for the increasing value of pressure gradient, porosity and permeability. On the contrary, the flow rate is decreased in square duct channel compared to cylindrical channel for increasing value of viscosity. Flow rate in both channels is analyzed and compared for non-porous medium also. It is observed that flow rate is increased very high in cylindrical channel compared to square duct channel for both medium.
文摘Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work concerns the functional expression of gap junction protein connexin 43 (Cx43) in normal human lung cells and the changes in lung carcinoma cells. By. using Northern blot hybridization analysis and Cx43 immunocytochemical methods, it was otherved that cultured normal human embryonic lung cells expressed a high level of Cx43 in both mRNA and protein levels.The Cx43 immunofluorescence was localized at cell membrane regions corresponding to the location of gap junctions. These normal lung cells were competent of intercellular communication function as detected by Lucifer yellow dye transfer. In contrast to normal celis, Cx43 mRNA and protein was not detectable in the carcinoma PG cell line. These tumor cells were defective of intercellular communication function. These results demonstrate that Cx43 is expressed in normal cultured human embryonic lung cells but not in lung tumor cells. The lack of intercellular communication in the lung tumor cell line correlates with dysfunctional intercellular communication. The suggestive role of Cx as a tumor suppersor gene is discussed.
文摘Background Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug.Methods Survivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin)cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM).The protein expression levels of survivin, LRP, cyclin-D1, caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo.Results Survivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug-resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth.Conclusions Survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3.Anti-tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas.
基金This work was supported by a grant from National 973 Project (2001CB5102) for Outstanding Scholars of New Era from the Ministry of Education of China (2002-48)+1 种基金 National Natural Science Foundation of China (30000028) the key research program from Sc
文摘Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorp-tion/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load. The average deviation of spot position was 0.733±0.101 mm in IEF direction, and 0.925±0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190±72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls. Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduc-tion. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis. These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.
文摘Abnormally elevated activity of ornithine decarboxylase (ODC), and subsequent polyamine accumulation are intimately associated with the genesis.development and metastasis of cancer. In the present study, to control the growth of tumor cells, ODC antisense RNA was used to transfect human lung squamous carcinoma cell line LTEP-78. Compared with the parental cells, growth of the antisense transfected LTEP-78 cells arrested in G0/Gl phase and colony formation in soft agarose and tumorigenicity in nude mice were significantly reduced. Nucleic acid hybridization demonstrated that the transfectants expressed a high level of ODC antisense RNA and a significantly reduced level of endogenous ODC mRNA.The results suggest that the reversion of malignant phenotypes of human lung squamous carcinoma cells transfected with ODC antisense RNA is associated with the inhibition of polyamine biosynthesis.