• 제목/요약/키워드: Lung development

Search Result 788, Processing Time 0.034 seconds

GOLPH3, a Good Prognostic Indicator in Early-stage NSCLC Related to Tumor Angiogenesis

  • Lu, Ming;Tian, Yu;Yue, Wei-Ming;Li, Lin;Li, Shu-Hai;Qi, Lei;Hu, Wen-Si;Gao, Cun;Si, Li-Bo;Tian, Hui
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.14
    • /
    • pp.5793-5798
    • /
    • 2014
  • Background: Golgi phosphoprotein-3 (GOLPH3) is implicated in cancer development and progression. The aim of this study was to evaluate the prognostic significance of GOLPH3 protein and its association with tumor angiogenesis in patients with early-stage NSCLC. Materials and Methods: Immunohistochemistry was performed to determine GOLPH3 protein expression and allow assessment of intratumoral microvessel density (MVD) by counting CD-34 positive immunostained endothelial cells. Correlations of expression with MVD, clinicopathologic features and clinical prognosis were analyzed. Results: A notably higher level of GOLPH3 expression was found in early-stage NSCC tissues at the protein level. However, we do not find any correlation between GOLPH3 expression and clinicopathologic features (p>0.05), although higher MVD was positively associated with GOLPH3 overexpression (p<0.001). Expression of GOLPH3 was found to be an independent prognostic factor in early-stage NSCLC patients, those expressing high levels of GOLPH3 exhibiting a substantially lower 5-year overall survival than GOLPH3-negative patients (adjusted HR =1.899, 95% CI: 1.021-3.532, p=0.043). Conclusions: High expression of the GOLPH3 protein is common in early-stage NSCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. We conclude a possibility of its use as a diagnostic and prognostic marker in early-stage NSCC patients.

Fluorometric Detection of Low-Abundance EGFR Exon 19 Deletion Mutation Using Tandem Gene Amplification

  • Kim, Dong-Min;Zhang, Shichen;Kim, Minhee;Kim, Dong-Eun
    • Journal of Microbiology and Biotechnology
    • /
    • v.30 no.5
    • /
    • pp.662-667
    • /
    • 2020
  • Epidermal growth factor receptor (EGFR) mutations are not only genetic markers for diagnosis but also biomarkers of clinical-response against tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Among the EGFR mutations, the in-frame deletion mutation in EGFR exon 19 kinase domain (EGFR exon 19-del) is the most frequent mutation, accounting for about 45% of EGFR mutations in NSCLCs. Development of sensitive method for detecting the EGFR mutation is highly required to make a better screening for drug-response in the treatment of NSCLC patients. Here, we developed a fluorometric tandem gene amplification assay for sensitive detection of low-abundance EGFR exon 19-del mutant genomic DNA. The method consists of pre-amplification with PCR, thermal cycling of ligation by Taq ligase, and subsequent rolling circle amplification (RCA). PCR-amplified DNA from genomic DNA samples was used as splint DNA to conjugate both ends of linear padlock DNA, generating circular padlock DNA template for RCA. Long stretches of ssDNA harboring multiple copies of G-quadruplex structure was generated in RCA and detected by thioflavin T (ThT) fluorescence, which is specifically intercalated into the G-quadruplex, emitting strong fluorescence. Sensitivity of tandem gene amplification assay for detection of the EGFR exon 19-del from gDNA was as low as 3.6 pg, and mutant gDNA present in the pooled normal plasma was readily detected as low as 1% fraction. Hence, fluorometric detection of low-abundance EGFR exon 19 deletion mutation using tandem gene amplification may be applicable to clinical diagnosis of NSCLC patients with appropriate TKI treatment.

Development of Source Profiles for Asbestos and Non-asbestos Fibers by SEM/EDX (SEM/EDX를 이용한 석면 및 비석명의 오염원분류표 개발)

  • Choi, Young-A;Lee, Tae-Jung;Kim, Dong-Sool
    • Journal of Korean Society for Atmospheric Environment
    • /
    • v.23 no.6
    • /
    • pp.718-726
    • /
    • 2007
  • There are many varieties of asbestos: chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophylite. These are widely used in construction materials, brake lining, textile, and so on. Even though non-asbestos fibers such as glassfiber and rockwool have manufactured because asbestos causes asbestosis, lung cancer, mesothelioma, etc., some bad effects of non-asbestos have been also reported. PCM (phase contrast microscopy) and PLM (polarized light microscopy) have been used to qualitatively analyze asbestoses. These techniques have serious drawbacks when identifying and separating various asbestoses. Recently scanning electron microscopy (SEM) equipped with energy dispersive X-ray analysis (EDX) has been known as an useful tool to analyze airborne particle since it provides physical and chemical information simultaneously. The purpose of the study was to classify both asbestos and non-asbestos fibers and finally to develop their source profiles by using the SEM/EDX. The source profiles characterized by 6 different types of asbestos fibers and 2 types of non-asbestos fibers had been developed by analyzing a total of 380 fibers. Analytical parameters used in this study were length, width, aspect ratio, and shape as physical information, and Na, Mg, Al, Si, K, Ca, Cr, Mn, Fe, and Cu as chemical information. All the parameters were intensively reviewed.

Screening of Anti-cancer Compounds Originated from Filamentous Fungi (Monascus sp.) (사상성 곰팡이 (Monascus sp.) 유래 항암 물질의 탐색)

  • Sin, Yeong-Min;Park, Hae-Ryoun;An, Won-Gun
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.19 no.3
    • /
    • pp.671-676
    • /
    • 2005
  • In this study, we investigated the antioxidant effect of extract from Monascus pillosus, on the human wild-type p53 and p21 expressing A549 lung epithelial cell line and MCF-7 mammary adenocarcinoma cell line stimulated by NO. $P21^{waf/cip1}$ was identified as a gene induced in senescent cells. It is a cyclin-dependent kinase inhibitor and has been shown to cause cell cycle arrest and apoptosis. While p53-regulated stimulation of p21 appears to be central for the permanent growth-arrest, the role of p21 in p53-triggered cell death is unclear. Low dose of sodium nitroprusside (SNP) induced the development of senescence associated with increased expression of p53 and p21 in A549 cells. Inhibition of p21 transactivating activity requires high level correlates with the amount of p53 necessary to cause cell death. Association of p21 and p53 results in inhibition of p21-stimulated transcription. This requires a higher p53 level than is necessary for transcriptional activation of endogenous p53-responsive gene but correlates well with the level of p53 necessary to cause cell death. Exposure to W-1 inhibited oxidative stresses-induced senescence-like arrest, resulting in a significant reduction in p53 and p21 steady state levels. These results suggest that p53 and p21 play a central role in the onset of senescence. Thus, it is important to emphasize control of oxidative balance in tumor prevention and aging.

Experimental development of caprine enterotoxaemia with Clostridium perfringens type D whole culture in natural host and its treatments

  • Islam, Kbms;Rahman, Md Sidiqur;Ershaduzzaman, Md.;Taimur, Mjfa;Song, Hee-Jong
    • Korean Journal of Veterinary Service
    • /
    • v.30 no.2
    • /
    • pp.219-231
    • /
    • 2007
  • The effects of intraduodenal administration of Clostridium perfringens type D whole culture in goats were evaluated to develop a reliable experimental model of enterotoxemia in this species and the eventual evaluation of treatment with different drug preparations was also carried out. A total of 28 conventionally reared healthy unvaccinated black bangle goat kids of 6-12 months of age were dosed intraduodenally with whole cultures of C peliringens type D. Four kids were used as controls and received sterile, nontoxic culture medium intraduodenally. All animals received starch solution into the abomasum. The clinical signs developed within 12 hours of post inoculation that were similar to those observed in naturally occurring cases. Among the clinical signs, diarrhea was most common (96.43%) followed by dyspnea (53.57%) and central nervous system (CNS) signs (25.0%). The most striking postmortem findings consisted of necrotizing pseudomembranous colitis (100.0%), lung edema (69.23%) and fluid filled intestines (61.53%). The protocol thus provided a reasonable model of naturally occurring enterotoxemia in goats, producing a range of clinical signs and postmortem changes similar to those observed in the natural disease. Beside this, treatment trial with different drug preparations showed penicillin combined with antitoxin was most effective (100.0%), followed by combination of oxytetracyclin with antitoxin, and combined preparation of antitoxin and sulfur drugs both showed 75% recovery rate. On the other hand, treatment with antitoxin, penicillin and oxytetracycline singly could protect goat enterotoxaemia only 25.0%, 50.0% and 50.0%, respectively. Thus in the present study, it eas observed that antisera in combination of antibiotics gave better recovery rate than the antitoxin or antibiotics alone.

Detection of atypical porcine pestivirus (APPV) from a case of congenital tremor in Korea (포유자돈 선천성 진전증 증례에서 atypical porcine pestivirus (APPV) 검출)

  • Kim, Seung-Chai;Jeong, Chang-Gi;Yoon, Seung-Min;Lee, Ki-Ho;Yang, Myoun-Sik;Kim, Bumseok;Lee, Seung-Yoon;Kang, Seog-Jin;Kim, Won-Il
    • Korean Journal of Veterinary Service
    • /
    • v.40 no.3
    • /
    • pp.209-213
    • /
    • 2017
  • Congenital tremor (CT) is a sporadic neurodegenerative disease reported in suckling piglets worldwide. Since atypical porcine pestivirus (APPV) was first identified in US in 2015, it has also subsequently detected in Europe and China as a causative pathogen for CT in suckling piglets. Three new-born piglets died from severe tremor was submitted to Chonbuk National University-Veterinary Diagnostic Center (CBNU-VDC) and various tissues (lung, lymph node, brain, intestine) were tested with panpestivirus RT-PCR and APPV NS5B-specific RT-PCR. All of the samples were positive by both of the PCR tests and the partial NS5B sequences of APPV were confirmed by sequencing on the PCR products of APPV NS5B-specific RT-PCR. Therefore, we report the first identification of APPV from a case of CT in suckling piglets in Korea.

Genotoxicity Study on Khal, a Halocidin Derivative, in Bacterial and Mammalian Cells

  • Kim, Youn-Jung;Kim, Mi-Soon;Jeon, Hee-Kyoung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
    • /
    • v.2 no.3
    • /
    • pp.151-158
    • /
    • 2006
  • Khal was a synthetic congener of halocidin, a heterodimeric peptide consisting of 19 and 15 amino acid residues detected in Halocynthia aurantium. This compound was considered a candidate for the development of a novel peptide antibiotic. The genotoxicity of Khal was subjected to high throughput toxicity screening (HTTS) because they revealed strong antibacterial effects. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay and chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of Khal was determined the concentration of $25.51\;{\mu}/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, Khal was not induced DNA damage in mouse lymphoma cell line. Also, the mutation frequencies in the Khal-treated cultures were similar to the vehicle controls. It is suggests that Khal is non-mutagenic in MOLY assay. And no clastogenicity was observed in Khal-treated Chinese hamster lung cells. The results of this battery of assays indicate that Khal has no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that Khal, as the optimal candidates with both no genotoxic potential and antibacterial effects must be chosen.

Construction of an Exposure Risk Map and Spatial Knowledge Base for Asbestos in Korea (석면 공간지식베이스 구축을 통한 석면 노출위험도 작성)

  • Hwang, Jae-Hong;Lee, Byung-Joo
    • The Journal of Engineering Geology
    • /
    • v.21 no.4
    • /
    • pp.393-402
    • /
    • 2011
  • Asbestos is a toxic material that can lead to lung cancer and other diseases. There is no information regarding areas in Korea that contain asbestos in nature; consequently we need to manage such areas with care. The purpose of this study was to construct a local graded map of asbestos exposure risk based on the natural occurrence of asbestos in rocks. We first developed a means of evaluating the asbestos exposure risk and produced thematic maps based on a field survey. In addition, we constructed a knowledge base for asbestos through analysis, representation and processes about asbestos data and prepare for the development of an evaluation model for asbestos exposure risk. The spatial analysis of asbestos exposure risk is based on a weighted-overlay analysis using expert opinion and the literature, and a fuzzy-overlay analysis using the uncertainty in the data. The map of asbestos exposure risk, compiled according to the weighted and fuzzy operations, is expected to be used to ensure safety and to reduce the risk of exposure to asbestos.

Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells

  • Do, Nam Yong;Shin, Hyun-Jae;Lee, Ji-Eun
    • Nutrition Research and Practice
    • /
    • v.11 no.2
    • /
    • pp.83-89
    • /
    • 2017
  • BACKGROUND/OBJECTIVES: Epithelial-mesenchymal transition (EMT) is involved in not only cancer development and metastasis but also non-cancerous conditions. Hypoxia is one of the proposed critical factors contributing to formation of chronic rhinosinusitis or nasal polyposis. Wheatgrass (Triticum aestivum) has antioxidant, anti-aging, and anti-inflammatory effects. In this study, we analyzed whether wheatgrass has an inhibitory effect on the EMT process in airway epithelial cells. MATERIALS/METHODS: A549 human lung adenocarcinoma cells were incubated in hypoxic conditions ($CO_2$ 5%/$O_2$ 1%) for 24 h in the presence of different concentrations of wheatgrass extract (50, 75, 100, and $150{\mu}g/mL$) and changes in expression of epithelial or mesenchymal markers were evaluated by immunoblotting and immunofluorescence. Accordingly, associated EMT-related transcriptional factors, Snail and Smad, were also evaluated. RESULTS: Hypoxia increased expression of N-cadherin and reduced expression of E-cadherin. Mechanistically, E-cadherin levels were recovered during hypoxia by silencing hypoxia inducible factor (HIF)-$1{\alpha}$ or administering wheatgrass extract. Wheatgrass inhibited the hypoxia-mediated EMT by reducing the expression of phosphorylated Smad3 (pSmad3) and Snail. It suppressed the hypoxia-mediated EMT processes of airway epithelial cells via HIF-$1{\alpha}$ and the pSmad3 signaling pathway. CONCLUSION: These results suggest that wheatgrass has potential as a therapeutic or supplementary agent for HIF-1-related diseases.

The Effect of Tumor Necrosis Factor (TNF) on Gene Expression of Surfactant Protein A, B, and C (Tumor Necrosis Factor가 Surfactant Protein A, B, C의 유전자 발현에 미치는 영향에 관한 실험적 연구)

  • Choi, Jin-Won;Sohn, Jang-Won;Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo
    • Tuberculosis and Respiratory Diseases
    • /
    • v.48 no.4
    • /
    • pp.513-521
    • /
    • 2000
  • Background : TNF may play an important role(central mediator) in the development of an acute respiratory distress syndrome. Since TNF induced lung injury in the acute respiratory distress syndrome and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of TNF on the regulation of surfactant protein A, B and C mRNA accumulation. Methods : The effects of TNF on gene expression of surfactant protein A, B, and C were analyzed using filter hybridization, 12 and 24 hours after intravenous injection of TNF in rats. Results : 1. The accumulation of SP-A mRNA in the TNF treated group (12 and 24 hours after TNF injection) was significantly decreased by 22.9% and 27.4%, respectively, compared to the control group (P<.025, P<.025). 2. The accumulation of SP-B mRNA in 24 hours after TNF treated group was significantly decreased by 20.5% compared to that of the control group(P<.01). 3. The accumulation of SP-C mRNA in 12 hours after TNF treated group was significantly decreased by 31% the compared to that of the control group(P<.01). Conclusions : These findings indicate the marked inhibitory effects of tumor necrosis factor on surfactant proteins expression in vivo. This finding. in turn, supports the idea of inhibitory effects of tumor necrosis factor on surfactant proteins expression as it relates to pathogenesis of acute respiratory distress syndrome.

  • PDF