• Title/Summary/Keyword: Reverse cycle

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H9 Inhibits Tumor Growth and Induces Apoptosis via Intrinsic and Extrinsic Signaling Pathway in Human Non-Small Cell Lung Cancer Xenografts

  • Kim, Min-Je;Kwon, Sae-Bom;Ham, Seung Hoon;Jeong, Eui-Suk;Choi, Yang-Kyu;Choi, Kang Duk;Hong, Jin Tae;Jung, Seung Hyun;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.25 no.5
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    • pp.648-657
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    • 2015
  • H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

Differential Expressions of Adhesion Receptor Genes in the Rat Uterus Associated with Ovarian Steroid Hormone (흰쥐 자궁에서 난소 스테로이드 호르몬에 의한 Adhesion 수용체 유전자 발현조절에 대한 연구)

  • Kang Han Seung;Lee Chae Kwan;Moon Deog Hwan;Kang Sung Goo
    • Development and Reproduction
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    • v.7 no.1
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    • pp.41-48
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    • 2003
  • This report aimed at investigating the differential gene expressions of the adhesion receptors between ovariectomized (OVX) and estrus stage rat uteri (OVX vs. estrus pair) using the cDNA expression away analysis. In addition, this report aimed at confirming of the differential gene expressions of the adhesion receptors between OVX and progesterone (P$_4$) injected OVX rat uteri (OVX vs. OVX+P$_4$ pair). RNA samples were extracted from the uterus and reverse-transcribed in the presence of [$\alpha$$^{32}$ P]-dATP. Membrane sets of Rat Atlas array 1.2 II (Clontech) were hybridized with CDNA probe sets. RT-PCR was employed to validate the relative gene expression patterns obtained by the cDNA array. The results were well consistent to cDNA array analysis data except the fold changes of gene expression. Among a total of 1176 cDNAs, 5 genes of adhesion receotor including embigin protein, activated leukocyte cell adhesion molecule, afadin, neuroligin 2, semaphorin Z showed significant (more than 2-fold) changes in the OVX vs. late estrus pair. All of these genes were up regulated in estrus stage than OVX rat uterus. In the OVX vs. OVX+P$_4$ pair, 4 genes including osteonectin, afadin, neuroligin 2, semaphorin Z showed significant changes. All of these genes were also up regulated in OVX+P$_4$ injected rat uterus than OVX control. Three genes including afadin, neuroligin 2, semaphorin Z which were up regulated in estrus and OVX+P$_4$ injected rat uteri of both experimental pairs than OVX rat uteri. These genes seem to be under the control of P$_4$.

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Cucurbitacin-I, a Naturally Occurring Triterpenoid, Inhibits the CD44 Expression in Human Ovarian Cancer Cells (난소암 세포주의 CD44 발현에 미치는 Cucurbitacin-I의 효과)

  • Seo, Hee Won;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.28 no.6
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    • pp.733-737
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    • 2018
  • Cucurbitacin-I, a natural triterpenoid derived from Cucurbitaceae family plants, exhibits a number of potentially useful pharmacological and biological activities. Indeed, the previous study demonstrated that cucurbitacin-I reduced the proliferation of colon cancer cells by enhancing apoptosis and causing cell cycle arrest at the G2/M phase. CD44, a type I transmembrane protein with the function of adhering to cells, mediates between the extracellular matrix and other cells through hyaluronic acid. Recent studies have demonstrated that an overexpression of the CD44 membrane receptor results in tumor initiation and growth, specific behaviors of cancer stem cells, the development of drug resistance, and metastasis. The aim was to examine the effect of cucurbitacin-I on CD44 expression human ovarian cancer cells because the effect of cucurbitacin-I on CD44 expression has not been reported. The expressions of CD44 mRNA and protein were detected using a quantitative real-time reverse-transcription polymerase chain reaction and a Western blot analysis, respectively. Treatment with cucurbitacin-I inhibited the expression of CD44 mRNA and protein. A subsequent analysis revealed that cucurbitacin-I blocked the phosphorylation of activator protein-1 (AP-1) and nuclear factor kappa-B ($NF-{\kappa}B$), which are key regulators of CD44 expression. Taken together, the data demonstrate that cucurbitacin-I regulates the AP-1 and $NF-{\kappa}B$ signaling pathways, leading to decreased CD44 expression.

Transcriptome Profiling of Kidney Tissue from FGS/kist Mice, the Korean Animal Model of Focal Segmental Glomerulosclerosis (국소성 분절성 사구체 신병증의 동물 모델 (FGS/kist 생쥐) 신 조직의 유전자 발현 양상)

  • Kang, Hee-Gyung;Lee, Byong-Sop;Lee, Chul-Ho;Ha, Il-Soo;Cheong, Hae-Il;Choi, Yong
    • Childhood Kidney Diseases
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    • v.15 no.1
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    • pp.38-48
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    • 2011
  • Purpose: Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy causing pediatric renal failure. Since specific treatment targeting the etiology and pathophysiology of primary FSGS is yet elusive, the authors explored the pathophysiology of FSGS by transcriptome analysis of the disease using an animal model. Methods: FGS/kist strain, a mouse model of primary FSGS, and RFM/kist strain, as control and the parent strain of FGS/kist, were used. Kidney tissues were harvested and isolated renal cortex was used to extract mRNA, which was run on AB 1700 mouse microarray chip after reverse transcription to get the transcriptome profile. Results: Sixty two genes were differentially expressed in FGS/kist kidney tissue compared to the control. Those genes were related to cell cycle/cell death, immune reaction, and lipid metabolism/vasculopathy, and the key molecules of their networks were TNF, IL-6/4, IFN${\gamma}$, TP53, and PPAR${\gamma}$. Conclusion: This study confirmed that renal cell death, immune system activation with subsequent fibrosis, and lipid metabolism-related early vasculopathy were involved in the pathophysiology of FSGS. In addition, the relevance of methodology used in this study, namely transcriptome profiling, and Korean animal model of FGS/kist was validated. Further study would reveal novel pathophysiology of FSGS for new therapeutic targets.

A Study on the Application of Ion Crystallization Technology to the APR 1400 Liquid Waste Management System (핵종 이온 광물화 처리기술의 APR 1400 발전소 액체방사성폐기물관리계통 적용 위치에 대한 고찰)

  • Go, Kyung-Min;Kim, Chang-Lak
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.17 no.4
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    • pp.419-427
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    • 2019
  • The application of ion crystallization technology was considered as a way to increase the operating efficiency and improve the operating performance of a liquid waste management system (LWMS) in the Advanced Power Reactor 1400 (APR 1400). Although ion crystallization technology has not been practically applied to Nuclear Power Plants (NPPs) until now, a previous experimental study demonstrated that it is possible to selectively remove at least 95% of various nuclide ions present in the liquid radioactive waste of NPPs. We reviewed the possibility of applying ion crystallization technology to the existing LWMS by applying the nuclide removal rate of ion crystallization technology and prepared a way to improve the existing LWMS in the APR 1400. Furthermore, we determined the optimized application location of ion crystallization technology in the existing LWMS by considering decontamination characteristics of the ion crystallization technology and the existing LWMS design features and operating experiences. The application of ion crystallization technology to the liquid waste collection tank, where liquid radioactive materials are collected, will have the least impact on the existing design while providing the greatest improvement. It is expected that the application of ion crystallization technology to the current APR 1400 or new NPPs would increase the operating efficiency of the LWMS and result in an improvement of system performance.

Detection of Differentially Expressed Genes in Glioblastoma by Suppression Subtractive Hybridization

  • Yu, Na-Mi;Ahn, Jung-Yong;Choi, Eun-Jin;Hong, Yong-Kil;Kim, Tai-Gyu;Kim, Chang-Hyun;Lee, Kyu-Sung;Kim, Dong-Seok;Kim, Jin-Kyeoung
    • Journal of Korean Neurosurgical Society
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    • v.37 no.6
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    • pp.443-448
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    • 2005
  • Objective: A variety of genetic alterations in human glioblastoma comprises signal transduction and cell cycle arrest control of cellular processes. Subtractive hybridization is potentially a faster method for identifying differentially expressed genes associated with a particular disease state. Using the technique of subtraction, we isolated novel genes that are overexpressed in glioblastoma tissue as compared to normal brain tissue. Methods: We evaluated the differential expression of genes in each of hybridizing tester and driver cDNAs to digested 130 clones. After sequencing of 130 clones and homology search, this study performed to determine mRNA expression of the unknown gene, "clone 47", in brain tissue, glioblasoma, and several cancer cell lines by reverse transcription-polymerase chain reaction (RT-PCR). To test the time course for Go-phase arrest, serum stimulation and expression at various times for RT-PCR performed. Results: We identified 23 novel genes by BLAST of the digested 130 clones. The expressions of "clone 47" mRNA of glioblastoma and several cancer lines were significantly higher than normal brain tissues and several normal cell lines. We confirmed the mRNA expression of "clone 47" was up-regulation for $0.5{\sim}1hr$ of WI-38 cell differentiation. Conclusion: The novel gene, "Clone 47" is upregulated in glioblastoma tissue and several cancer cell lines. This gene is time dependent activation during time course of serum stimulation. This result suggests that "clone 47" playa role in brain tumorigenesis and the activation of this "clone 47" may be necessary for the development of cancer.

Diagnostic Techniques for SARS-CoV-2 Detection (SARS-CoV-2의 진단기술)

  • Kim, Jong-Sik;Kang, Na-Kyung;Park, Seon-Mi;Lee, Eun-Joo;Chung, Kyung Tae
    • Journal of Life Science
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    • v.30 no.8
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    • pp.731-741
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    • 2020
  • Coronavirus disease 19 (COVID-19) is caused by SARS-CoV-2 (Severe Acute Respiratory SyndromeCoronavirus 2). To date, seven coronaviruses that can infect humans were reported. Among them, infections with four coronavirus strains (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1) resulted in mild symptoms such as common cold, whereas SARS-CoV and MERS-CoV caused severe symptoms and epidemics in 2002 and 2012, respectively. In the most recent, SARS-CoV-2 was first reported in Wuhan, China in December 2019 and became a notorious cause of the ongoing global pandemics. To diagnose, treat, and prevent COVID-19, the development of rapid and accurate diagnostic tools, specific therapeutic drugs, and safe vaccines essentially are required. In order to develop these powerful tools, it is prerequisite to understand a phenotype, a genotype, and life cycle of SARS-CoV-2. Diagnostic techniques have been developing rapidly around world and many countries take the fast track system to accelerate approval. Approved diagnostic devices are rapidly growing facing to urgent demand to identify carriers. Currently developed commercial diagnostic devices are divided into mainly two categories: molecular assay and serological & immunological assay. Molecular assays begins the reverse transcription step following polymerase chain reaction or isothermal amplification. Immunological assay targets SARS-CoV-2 antigen or anti-SARS-CoV-2 antibody of samples. In this review, we summarize the phenotype, genome structure and gene expression of SARS-CoV-2 and provide the knowledge on various diagnostic techniques for SARS-CoV-2.

Anti-proliferative Effects of Atractylis lancea (Thunb.) DC. via Down-regulation of the c-myc/hTERT/Telomerase Pathway in Hep-G2 Cells

  • Guo, Wei-Qiang;Li, Liang-Zhi;He, Zhuo-Yang;Zhang, Qi;Liu, Jia;Hu, Cui-Ying;Qin, Fen-Ju;Wang, Tao-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6363-6367
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    • 2013
  • Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentrationand time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the $IC_{50}$ was about 72.1 ${\mu}g/mL$. Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/telomerase pathway.

Expressions of Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptor Gene in the Rat Uterus (흰쥐 자궁에서 Pituitary Adenylate Cyclase-Activating Polypeptide와 수용체 유전자의 발현)

  • 이성호
    • Development and Reproduction
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    • v.2 no.1
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    • pp.21-27
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    • 1998
  • The present study was performed to analyze the gene expressions of pituitary adenylate cyclase-activating polypeptide(PACAP) and its receptor in the rat uterus, a candidate for novel extrahypothalamic source and target. The PACAP cDNA fragments corresponding to the common exon region which is found in both the rat hypothalamus and testis were produced from all tissue samples including the rat uterus by reverse transcriptionpolymerase chain reaction (RT-PCR). No PCR product was amplified from the rat hypothalamic, pituitary, ovarian and uterine samples when the 5' primer corresponding to the testis-specific exon 1 region was used, while the predicted size of product was detected from the testis sample. RT-PCR using the uterine RNA and specific primers for the PACAP receptor yielded products with predicted sizes. Transcripts for the rat uterine PACAP receptor were identified as type I isoforms with hip-hop and hip- or hop-type inserts. After pregnant mare's serum gonadotropin (15 IU) treatment of immature rats (day 25), the level of PACAP mRNA was increased in 24 h and 48 h group, and was declined to the lowest in 72 h group. The present study shows the presence of transcripts for PACAP and its receptor isoform in the rat uterus. These finding ssuggest that the uterine PACAP ight act as a novel autocrine and/or paracrine factor via its specific receptors on the reglulation of rat uterine function and physiology during the reproductive cycle.

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CCNG2 Suppressor Biological Effects on Thyroid Cancer Cell through Promotion of CDK2 Degradation

  • Li, Wei-Juan;Liu, Ge-Ling;Yu, Fang;Xiang, Xiu-Xiu;Lu, Yi-Fang;Xiao, Hong-Zhen;Shi, Yan-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6165-6171
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    • 2013
  • This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.