OBSERVATIONS ON MANGANESE-CONTAINING SUPERO- XIDE DISMUTASE ACTIVITY IN HUMAN LUNG CANCER

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.

Highly Efficient Labeling of Human Lung Cancer Cells Using Cationic Poly-L-lysine-Assisted Magnetic Iron Oxide Nanoparticles

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.

Anticancer actions of PPARγ ligands:Current state and future perspectives in human lung cancer

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.

Alteration of Gene Expression Profile and Signal Pathway Induced by Methylseleninic Acid in Human Lung Cancer Cell Lines

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

The Role of CHMP4C on Proliferation in the Human Lung Cancer A549 Cells

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.

IONIZING RADIATION-INDUCED IL-Ia, IL-6 AND GM-CSF PRODUCTION BY HUMAN LUNG CANCER CELLS

A cell line derived from human lung cancer(AOI) was employed in the present study.A panel of cytokines were quantified by ELISA technique following cellular exposure to X-irradiation.

Combined therapy of p53-wt and drug in an orthotopic multidrug-resistant human lung cancer model

Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d after tumor cell inoculation, 75% of the control mice showed macroscopic tumors in the lung. Sole pDOR53W suppressed GLK tumor formation in 68 % of mice; sole doxorubicin 33. 3 % , but the combination of pDOR53W and doxorubicin 88.9%. The exogenous p53 sequence was detected and confirmed in the tumor that grew after treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization with p53 cDNA. These results suggested that di-rect administration of a retroviral vector expressing p53-wt combined with treatment of anticancer agent was an effec-tive therapeutic method for multidrug-resistant human lung cancer.

Antitumor effect of recombinant human endostatin combined with cisplatin on rats with transplanted Lewis lung cancer

Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.

Reversal of drug resistance of multidrug-resistant human lung cancer cells by an MDR1 ribozyme

MALIGNANT tumor is very harmful to human health, and the mortality is very high. About 50% of the patients with malignancy can be operated on, and the other 50% patients have to be treated with chemotherapy. Because tumors are mostly chemoresistant, chemotherapy for these patients often has no effect. The overexpression of MDR1 gene is very common in hu man malignant tumors, about 50% in previously untreated patients and more than 50% in previously treated patients for whom the tumor is resistant to the previous sensitive

Increasing drug resistance in human lung cancer cells by mutant-type p53 gene mediated by retrovirus

Human mutant-type (mt) p53 cDNA was synthesized and cloned from human lung cancer cell line GL containing mt-p53 gene by using polymerase chain reaction (PCR). It was confirmed that the mt-p53 cDNA con-tained the complete coding sequence of p53 gene but mutated at codon 245 (G→T) and resulted in glycine to cysteine by sequencing analysis. The retroviral vector pD53M of the mt-p53 was constructed and introduced into the drug-sen-sitive human lung cancer cells GAO in which p53 gene did not mutate. The transfected GAO cells strongly expressed mutant-type p53 protein by immunohistochemistry, showing that pD53M vector could steadily express in GAO cells. The drug resistance to several anticancer agents of GAO cells infected by pD53M increased in varying degrees, with the highest increase of 4-fold, in vitro and in vivo. By quantitative PCR and flow cytometry (FCM) analyses, the expression of MDR1 gene and the activity of P-glycoprotein (Pgp) did not increase, the expression of MRP gene and the activity of multidrug resistance-related protein (Mrp) increased slightly. These results indicated that the drug re-sistance associated with mt-p53 gene might be somewhat correlated with MRP/Mrp but not with MDR1/Pgp. It was possible to modify the tumor drug resistance by changing status of p53 gene.

The Difference of Gene Expression Prof ile in Human Large Cell Lung Cancer Cell Lines with Different Metastatic Potential

Background and Objective Lung cancer is the most lethal malignangy that threatens human heath and lives nowadays in the world, and meanwhile is also the one with worst

Noninvasive Assessment of Using Bioluminescent Imaging(BLI) to Research Methylseleninic Acid' Effect on the Growth And Spontaneous Metastasis in Human High-Metastatic Large Cell Lung Cancer Cell Line L9981

Background and Objective The disease incidence and mortality of lung cancer has been increased dramatically for recent 50 years in many countries in the world. In2002, the new cases

Effects of Methylseleninic Acid on the Proliferation and Cell Cycle in Human High Metastatic Large Cell Lung Cancer Cell Line L9981 and Its Molecular Mechanism

Background and Objective Lung cancer is the rst killer of human being in the whole world. Recently, although many treatment strategies have been developed, the anti-cancer effects

Methylseleninic Acid on The Apoptosis Induction and Invasion Inhibition in Human High-Meta-static Large Cell Lung Cancer Cell Line L9981

Background and Objective Lung cancer, which has been proved to have fastest increasing rate of morbidity and mortality, appears to be one of the most dangerous malignant tumor that

The Difference of the Copy Number Variation and Loss of Heterozygosity of Human Lung Large Cell Cancer Cell Line with Different Metastatic Potential

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

An Integrated Simulation System Based on Digital Human Phantom for 4D Radiation Therapy of Lung Cancer

Purpose: To develop and test an integrated simulation system based on the digital Extended Cardio Torso (XCAT) phantom for 4-dimensional (4D) radiation therapy of lung cancer. Methods: A computer program was developed to facilitate the characterization and implementation of the XCAT phantom for 4D radiation therapy applications. To verify that patient-specific motion trajectories are reproducible with the XCAT phantom, motion trajectories of the diaphragm and chest were extracted from previously acquired MRI scans of five subjects and were imported into the XCAT phantom. The input versus the measured trajectories was compared. Simulation methods of 4D-CT and 4D-cone-beam CT (CBCT) based on the XCAT phantom were developed and tested for regular and irregular respiratory patterns. Simulation of 4D dose delivery was illustrated in a simulated lung stereotactic-body radiation therapy (SBRT) case based on the XCAT phantom. Dosimetric comparison was performed between the planned dose and simulated delivered dose. Result: The overall mean (±standard deviation) difference in motion amplitude between the input and measured trajectories was 1.19 (±0.79) mm for the XCAT phantoms with voxel size of 2 mm. 4D-CT and 4D-CBCT images simulated based on the XCAT phantom were validated using regular respiratory patterns and tested for irregular respiratory patterns. Comparison between simulated 4D dose delivery and planned dose for the lung SBRT case showed comparable results in all dosimetric matrices: the relative differences were 0.3%, 4.0%, 0%, and 2.8%, respectively, for max cord dose, max esophagus dose, mean heart dose, and V20Gy of the lungs. 97.5% of planning target volume (PTV) received prescription dose in the simulated 4D delivery, as compared to 95% of PTV received prescription dose in the plan. Conclusion: We developed an integrated simulation system based on the XCAT digital phantom and illustrated its utility in 4D radiation therapy of lung cancer. This simulation system is potentially a useful tool for quality control and development of imaging and treatment techniques for 4D radiation therapy of lung cancer.

The Effects of Intracellular Glutathione Content on the Sensitivity of Methylseleninic Acid to Human High-metastatic Large Cell Lung Cancer Cell Line L9981

Background and Objective Lung cancer has the fastest increasing rate of morbidity and mortality all over the world and appears to be one of the most dangerous malignant tumors

Down-regulation and It's Molecular Biology of Nm-23H1 gene Transfection on Ras-to-MAPK Signal Transduction Pathway in Human High-metastatic Large Cell Lung Cancer Cell Line L9981

Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the key cause of failure to cure and lose their life of the patients

Alterations and Its Mechanisms of Wnt Signal Pathway in Human High-matastatatic Large Cell Lung Cancer Cell Line L9981 by Transfecting with Nm23-H1 Gene

Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the

Influence of Nm23-H1 Gene Site Mutagenesis on Invasive And Metastatic Phenotype in Human High-Metastatic Large Cell Lung Cancer Cell Line L9981

Background and Objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. To study and elucidate the molecular mechanism