• Title/Summary/Keyword: Non-small cell

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Radiosensitization Effect of Overexpression of Adenovirus-mediated SIRT6 on A549 Non-small Cell Lung Cancer Cells

  • Cai, Yong;Sheng, Zhao-Ying;Liang, Shi-Xiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7297-7301
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    • 2014
  • Objective: To explore the radiosensitization effect of overexpression of silent information regulator 6 (SIRT6) on A549 non-small cell lung cancer (NSCLC) cells. Methods: Adenovirus vector Ad-SIRT6 causing overexpression of SIRT6 was established. Western blotting and MTT assay were adopted to detect the level of SIRT6 protein and the inhibitory rate of A549 cell proliferation after different concentrations of adenovirus transduction (0, 25, 100, 200, and 400 pfu/cell) for 24 h. Control group, Ad-null group and Ad-SIRT6 group were designed in this experiment and virus concentration of the latter two groups was 200 pfu/cell. Colony formation assays were employed to test survival fraction (SF) of the 3 groups after 0, 2, 4, 6, 8, 10 X-ray irradiation. Flow cytometry was used to detect the status of cell cycle of 3 groups after 48 h of 4Gy X-ray irradiation and Western blotting was used to determine the expression of apoptosis-related genes of 3 groups after 48 h of 4GyX-ray irradiation. Results: In the range of 25~400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised. The inhibitory rates under the concentrations of 0, 25, 100, 200, and 400 pfu/cell were 0%, $4.23{\pm}0.34%$, $12.7{\pm}2.57%$, $22.6{\pm}3.38%$, $32.2{\pm}3.22%$, $38.7{\pm}4.09%$ and $47.8{\pm}5.58%$ and there were significantly differences among groups (P<0.05). SF in Ad-SIRT6 group was lower than Ad-null and control groups after 4~10Gy X-ray irradiation (P<0.05) and the sensitization enhancement ratio (SER) was 1.35 when compared with control group. Moreover, after 48 h of 4Gy X-ray irradiation, there appeared a significant increase in G1-phase cell proportion, upregulated expression of the level of apoptosis-promoting genes (Bax and Cleaved caspase-3), but a obvious decline in S-phase and G2-phase cell proportion and a significant decrease of the level of apoptosis-inhibiting gene (Bal-2) in the Ad-SIRT6 group (P<0.05). Conclusion: The over-expression of adenovirus-mediated SIRT6, which has radiosensitization effect on A549 cells of NSCLC, can inhibit the proliferation of A549 cells and cause G0/G1 phase retardation as well as induce apoptosis of cells.

Preoperative Staging in Non-Small Cell Lung Cancer without Lymphadenopathy on Computed Tomogram (흉부 전산화 단층촬영상 임파절종대가 없는 비소세포암 환자에 있어서 술전 병기판정)

  • Cha, Seung-Ick;Kim, Chang-Ho;Park, Jae-Yong;Jung, Tae-Hoon;Chang, Bong-Hyun;Kang, Duk-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.6
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    • pp.616-623
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    • 1994
  • Objectives: Careful evaluation about mediastinal involvement is important in the management of patients with non-small cell lung cancer. Invasive staging procedure such as mediastinoscopy is advocated because of the unreliability of noninvasive staging methods such as CT, MRI. We compared differences between pre- and postoperative staging in non-small cell lung cancer without lymphadenopathy on CT scan and investigated the methods for more accurate preoperative staging. Methods & Results: 1) Records of a total of 41 patients with preoperative $T_{1-3}N_0M_0$ non-small cell lung cancer were reviewed and the histologic types of tumors were squamous cell carcinoma in 32 cases, adenocarcinoma in 6 cases and large cell carcinoma in 3 cases. Twenty-four cases were central lesions and seventeen cases were peripheral lesions. 2) Among the 32 cases with preoperative $T_2$, 2 cases were identified postoperatively as $T_3$ with invasion of chest wall and among 6 cases with preoperative $T_3$, 1 case was identified postoperatively as $T_4$ with invasion of aorta and pulmonary arteries. 3) After the operation of 35 cases with $T_{1-2}$, 5 cases were $N_1$ and 3 cases were $N_2$ postoperatively. After the operation of 6 cases with $T_3$, 2 cases were $N_1$ and 3 cases were $N_2$ postoperatively. Preoperative $T_3$ showed more intrathoracic lymph node metastases and higher $N_2/N_1$ involvement ratio than preoperative $T_{1-2}$. 4) Complete surgical resections were done in 34 out of 41 cases. Incomplete resection were done in all postoperative $N_2$ tumors. Conclusion: Invasive staging procedures such as mediastinoscopy should be considered in the case of preoperative $T_3$ non-small cell lung cancer even though mediastinal lymphadenopathy is not recognized on the CT scan of the chest.

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Immunohistochemical Study of NSE in Small Cell Lung Cancer (SCLC) Combined with Serum Assay (소세포폐암에서 Neuron Specific Enolase의 면역조직 화학염색과 혈청농도에 관한 연구)

  • Kwak, Seung-Min;Kim, Hyung-Jung;Shin, Dong-Hwan;Jang, Joong-Hyun;Lee, Hong-Lyeol;Kim, Se-Kyu;Ahn, Chul-Min;Kim, Sung-Kyu;Lee, Won-Young;Lee, Kyi-Beom
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.6
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    • pp.502-510
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    • 1992
  • Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

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Loss of the Retinoblastoma Gene in Non-Small Cell Lung Cancer (비소세포폐암에서의 망막모세포종유전자의 소실)

  • Lee, Choon-Taek;Kim, Chang-Min;Zo, Jae-Ill;Shim, Young-Mog;Hong, Weon-Seon;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.98-103
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    • 1993
  • Background: Inactivation of retinoblastoma gene (Rb) has been observed in a variety of human cancers. Loss of heterozygosity (LOH) of Rb which is a common mode of allelic inactivation of Rb, has been known as a frequent genetic event in small cell lung cancer but it has been detected less frequently in non-small cell lung cancer. To define the role of Rb deletion in lung cancer, we investigated the genomic DNAs of 43 non-small cell lung cancers and 1 small cell lung cancer paired with normal lung tissues obtained by thoracotomy. Methods: The genomic DNAs were obtained by the digestion with proteinase K followed by phenol-chloroform extraction method. The genomic DNAs were digested by restriction endonuclease (EcoRI), separated by agarose gel electrophoresis, transferred to nylon membrane by Southern blot transfer and then hybridized with labelled Rb 1 probe which contains. 1.4 kb sized DNA sequence containing N-terminal portion of Rb. Results: In 26 squamous cell lung cancers, 16 cases were informative after EcoRI digestion and LOH of Rb was found in 10 cases (62.5%). In 17 adenocarcinomas of lung, 11 cases were informative and LOH of Rb was found in five cases (45.4%). The analysis of clinical parameters revealed no significant differences between the two groups with or without LOH of Rb in the aspects of age, sex, degree of differentiation, stage and smoking amount. Conclusions: These results suggest that Rb inactivation is also significantly involved in the molecular pathogenesis of non-small cell lung cancer.

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Cell clusters in intervertebral disc degeneration: an attempted repair mechanism aborted via apoptosis

  • Polly Lama;Jerina Tiwari;Pulkit Mutreja;Sukirti Chauhan;Ian J Harding;Trish Dolan;Michael A Adams;Christine Le Maitre
    • Anatomy and Cell Biology
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    • v.56 no.3
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    • pp.382-393
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    • 2023
  • Cell clusters are a histological hallmark feature of intervertebral disc degeneration. Clusters arise from cell proliferation, are associated with replicative senescence, and remain metabolically, but their precise role in various stages of disc degeneration remain obscure. The aim of this study was therefore to investigate small, medium, and large size cell-clusters. For this purpose, human disc samples were collected from 55 subjects, aged 37-72 years, 21 patients had disc herniation, 10 had degenerated non-herniated discs, and 9 had degenerative scoliosis with spinal curvature <45°. 15 non-degenerated control discs were from cadavers. Clusters and matrix changes were investigated with histology, immunohistochemistry, and Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Data obtained were analyzed with spearman rank correlation and ANOVA. Results revealed, small and medium-sized clusters were positive for cell proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) in control and slightly degenerated human discs, while large cell clusters were typically more abundant in severely degenerated and herniated discs. Large clusters associated with matrix fissures, proteoglycan loss, matrix metalloproteinase-1 (MMP-1), and Caspase-3. Spatial association findings were reconfirmed with SDS-PAGE that showed presence to these target markers based on its molecular weight. Controls, slightly degenerated discs showed smaller clusters, less proteoglycan loss, MMP-1, and Caspase-3. In conclusion, cell clusters in the early stages of degeneration could be indicative of repair, however sustained loading increases large cell clusters especially around microscopic fissures that accelerates inflammatory catabolism and alters cellular metabolism, thus attempted repair process initiated by cell clusters fails and is aborted at least in part via apoptosis.

Preparation and Characteristics of a Matrix Retaining Electrolyte for a Phosphoric Acid Fuel Cell Using Non-volatile Solvent, NMP (비휘발성 용매(NMP)를 사용한 인산형 연료전지(PAFC)용 전해질 매트릭스 제조 및 특성)

  • 윤기현;양병덕
    • Journal of the Korean Ceramic Society
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    • v.37 no.1
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    • pp.26-32
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    • 2000
  • Preparation and characteristics of a matrix retaining electrolyte using SiC whisker, PES binder, and NMP(n-methyl-2-pyrrolidone) as a non-volatile solvent for a phosphoric acid fuel cell were investigated. The conditions of binder and plasticizer, and the effects of substituting a volatile solvent by a non-volatile solvent were also studied. The minimum amount of the binder was about 17 wt% for the proper bubble pressure and surrounding SiC whiskers. And the maximum amount of the plasticizer was about 10wt% to be fitted into the polymer chain of the binder. The matrix prepared by using a non-volatile solvent needed longer time to dry, and its pore size was smaller compared with that of the matrix prepared by using volatile solvent. The small pore size resulted in decrease of the overall pore volume. The ionic conductivity in the condition of the same thickness was decreased due to decrease of phosphoric acid absorbancy. As the internal resistance of the electrolyte increased, the fuel cell performance slightly decreased.

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Distributed Carrier Aggregation in Small Cell Networks: A Game-theoretic Approach

  • Zhang, Yuanhui;Kan, Chunrong;Xu, Kun;Xu, Yuhua
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.9 no.12
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    • pp.4799-4818
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    • 2015
  • In this paper, we investigate the problem of achieving global optimization for distributed carrier aggregation (CA) in small cell networks, using a game theoretic solution. To cope with the local interference and the distinct cost of intra-band and inter-band CA, we propose a non-cooperation game which is proved as an exact potential game. Furthermore, we propose a spatial adaptive play learning algorithm with heterogeneous learning parameters to converge towards NE of the game. In this algorithm, heterogeneous learning parameters are introduced to accelerate the convergence speed. It is shown that with the proposed game-theoretic approach, global optimization is achieved with local information exchange. Simulation results validate the effectivity of the proposed game-theoretic CA approach.

Thermal Convection Between Two Horizontal Plates with Small Amplitude Non-Uniform Temperatures (작은 진폭의 불균일 온도를 갖는 두 수평 평판 사이에서의 열 대류)

  • Yoo Joo-Sik;Kim Yong-Jin
    • Korean Journal of Air-Conditioning and Refrigeration Engineering
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    • v.16 no.11
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    • pp.999-1005
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    • 2004
  • Thermal convection between two horizontal walls kept at small amplitude nonuniform temperatures of the form, $T_L=T_1+a{\Delta}T$ sin kx and $T_U=T_2+b{\Delta}T\;sin(kx-{\beta})$ with a, $b{\ll}1$, is numerically investigated. When the Rayleigh number is small, an upright cell is formed between two walls at ${\beta}=0$; the cell is tilted at ${\beta}={\pi}/2$, and a flow with two-tier-structure cells occurs at ${\beta}={\pi}$. As the Rayleigh number is increased, Nusselt number increases smoothly for ${\beta}=0\;and\;{\pi}/2$, but increases rather steeply for ${\beta}={\pi}$ near the critical Rayleigh number ($Ra_c=1708$). When the wave number is small (k=0.5), multicellular convection occurs over one wave length, for all phase differences, and multiple solutions are found.

Plumbagin from Plumbago Zeylanica L Induces Apoptosis in Human Non-small Cell Lung Cancer Cell Lines through NF-κB Inactivation

  • Xu, Tong-Peng;Shen, Hua;Liu, Ling-Xiang;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2325-2331
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    • 2013
  • Objective: To detect effects of plumbagin on proliferation and apoptosis in non-small cell lung cancer cell lines, and investigate the underlying mechanisms. Materials and Methods: Human non-small cell lung cancer cell lines A549, H292 and H460 were treated with various concentrations of plumbagin. Cell proliferation rates was determined using both cell counting kit-8 (CCK-8) and clonogenic assays. Apoptosis was detected by annexin V/propidium iodide double-labeled flow cytometry and TUNEL assay. The levels of reactive oxygen species (ROS) were detected by flow cytometry. Activity of NF-${\kappa}B$ was examined by electrophoretic mobility shift assay (EMSA) and luciferase reporter assay. Western blotting was used to assess the expression of both NF-${\kappa}B$ regulated apoptotic-related gene and activation of p65 and $I{\kappa}B{\kappa}$. Results: Plumbagin dose-dependently inhibited proliferation of the lung cancer cells. The IC50 values of plumbagin in A549, H292, and H460 cells were 10.3 ${\mu}mol/L$, 7.3 ${\mu}mol/L$, and 6.1 ${\mu}mol/L$ for 12 hours, respectively. The compound concentration-dependently induced apoptosis of the three cell lines. Treatment with plumbagin increased the intracellular level of ROS, and inhibited the activation of NK-${\kappa}B$. In addition to inhibition of NF-${\kappa}B$/p65 nuclear translocation, the compound also suppressed the degradation of $I{\kappa}B{\kappa}$. ROS scavenger NAC highly reversed the effect of plumbagin on apoptosis and inactivation of NK-${\kappa}B$ in H460 cell line. Treatment with plumbagin also increased the activity of caspase-9 and caspase-3, downregulated the expression of Bcl-2, upregulated the expression of Bax, Bak, and CytC. Conclusions: Plumbagin inhibits cell growth and induces apoptosis in human lung cancer cells through an NF-${\kappa}B$-regulated mitochondrial-mediated pathway, involving activation of ROS.

Differences in the Prognostic Significance of the SUVmax between Patients with Resected Pulmonary Adenocarcinoma and Squamous Cell Carcinoma

  • Motono, Nozomu;Ueno, Masakatsu;Tanaka, Makoto;Machida, Yuichiro;Usuda, Katsuo;Sakuma, Tsutomu;Sagawa, Motoyasu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10171-10174
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    • 2015
  • Background: The purpose of this study was to determine the prognostic significance of the maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients undergoing surgical treatment for non-small cell lung cancer. Materials and Methods: Seventy-eight consecutive patients (58 with adenocarcinomas, 20 with squamous cell carcinomas) treated with potentially curative surgery were retrospectively reviewed. Results: The SUVmax was significantly higher in the patients with recurrent than with non-recurrent adenocarcinoma (p<0.01). However, among the patients with squamous cell carcinoma, there were no differences with or without recurrence (p=0.69). Multivariate analysis indicated that the SUVmax of adenocarcinoma lesions was a significant predictor of disease-free survival (p=0.04). In addition, an SUVmax of 6.19, the cut-off point based on ROC curve analysis of the patients with pathological IB or more advanced stage adenocarcinomas, was found to be a significant predictor of disease-free survival (p<0.01). Conclusions: SUVmax is a useful predictor of disease-free survival in patients with resected adenocarcinoma, but not squamous cell carcinoma. Patients with adenocarcinoma exhibiting an SUVmax above 6.19 are candidates for more intensive adjuvant therapy.