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Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas

  • Liu, Qiang;Dai, She-Jiao;Li, Hong;Dong, Lei;Peng, Yu-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8623-8629
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    • 2014
  • Background: As an important component of the NDC80 kinetochore complex, NUF2 is essential for kinetochore-microtubule attachment and chromosome segregation. Previous studies also suggested its involvement in development of various kinds of human cancers, however, its expression and functions in human hepatocellular carcinoma (HCC) are still unclear. Materials and Methods: In the present study, we aimed to test the hypothesis that NUF2 is aberrant in human HCCs and associated with cell growth. Results: Our results showed significantly elevated expression of NUF2 in human HCC tissues compared to adjacent normal tissues, and high expression of NUF2 in HCC cell lines. Using lentivirus-mediated silencing of NUF2 in HepG2 human HCC cells, we found that NUF2 depletion markedly suppressed proliferation and colony formation capacity in vitro, and dramatically hampered tumor growth of xenografts in vivo. Moreover, NUF2 silencing could induce cell cycle arrest and trigger cell apoptosis. Additionally, altered levels of cell cycle and apoptosis related proteins including cyclin B1, Cdc25A, Cdc2, Bad and Bax were also observed. Conclusions: In conclusion, these results demonstrate that NUF2 plays a critical role in the regulation of HCC cell proliferation and apoptosis, indicating that NUF2 may serve as a potential molecular target for therapeutic approaches.

Genetic Features of Lung Adenocarcinoma with Ground-Glass Opacity: What Causes the Invasiveness of Lung Adenocarcinoma?

  • Kim, Dohun;Lee, Jong-Young;Yoo, Jin Young;Cho, Jun Yeun
    • Journal of Chest Surgery
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    • v.53 no.5
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    • pp.250-257
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    • 2020
  • Background: Lung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD. Methods: LUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in nonGGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted. Results: Overall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation. Conclusion: In conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.

Luteolin attenuates migration and invasion of lung cancer cells via suppressing focal adhesion kinase and non-receptor tyrosine kinase signaling pathway

  • Masraksa, Wuttipong;Tanasawet, Supita;Hutamekalin, Pilaiwanwadee;Wongtawatchai, Tulaporn;Sukketsiri, Wanida
    • Nutrition Research and Practice
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    • v.14 no.2
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    • pp.127-133
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    • 2020
  • BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

Postdischarge growth assessment in very low birth weight infants

  • Park, Joon-Sik;Han, Jungho;Shin, Jeong Eun;Lee, Soon Min;Eun, Ho Seon;Park, Min-Soo;Park, Kook-In;Namgung, Ran
    • Clinical and Experimental Pediatrics
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    • v.60 no.3
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    • pp.64-69
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    • 2017
  • Purpose: The goal of nutritional support for very-low-birth-weight (VLBW) infants from birth to term is to match the in utero growth rates; however, this is rarely achieved. Methods: We evaluated postdischarge growth patterns and growth failure in 81 Korean VLBW infants through a retrospective study. Weight and height were measured and calculated based on age percentile distribution every 3 months until age 24 months. Growth failure was defined as weight and height below the 10th percentile at 24 months. For the subgroup analysis, small-for-gestational age (SGA) and extremely low birth weight (ELBW) infants were evaluated. The growth patterns based on the Korean, World Health Organization (WHO), or Centers for Disease Control and Prevention (CDC) standard were serially compared over time. Results: At postconception age (PCA) 40 weeks, 47 (58%) and 45 infants (55%) showed growth failure in terms of weight and height, respectively. At PCA 24 months, 20 infants (24%) showed growth failure for weight and 14 (18%) for height. Growth failure rates were higher for the SGA infants than for the appropriate-weight-for-gestational age infants at PCA 24 months (P=0.045 for weight and P=0.038 for height). Growth failure rates were higher for the ELBW infants than for the non-ELBW infants at PCA 24 months (P<0.001 for weight and P=0.003 for height). Significant differences were found among the WHO, CDC, and Korean standards (P<0.001). Conclusion: Advancements in neonatal care have improved the catch-up growth of VLBW infants, but this is insufficient. Careful observation and aggressive interventions, especially in SGA and ELBW infants, are needed.

Health Indicators Related to Disease, Death, and Reproduction

  • Choi, Jeoungbin;Ki, Moran;Kwon, Ho Jang;Park, Boyoung;Bae, Sanghyuk;Oh, Chang-Mo;Chun, Byung Chul;Oh, Gyung-Jae;Lee, Young Hoon;Lee, Tae-Yong;Cheong, Hae Kwan;Choi, Bo Youl;Park, Jung Han;Park, Sue K.
    • Journal of Preventive Medicine and Public Health
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    • v.52 no.1
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    • pp.14-20
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    • 2019
  • One of the primary goals of epidemiology is to quantify various aspects of a population's health, illness, and death status and the determinants (or risk factors) thereof by calculating health indicators that measure the magnitudes of various conditions. There has been some confusion regarding health indicators, with discrepancies in usage among organizations such as the World Health Organization the, Centers for Disease Control and Prevention (CDC), and the CDC of other countries, and the usage of the relevant terminology may vary across papers. Therefore, in this review, we would like to propose appropriate terminological definitions for health indicators based on the most commonly used meanings and/or the terms used by official agencies, in order to bring clarity to this area of confusion. We have used appropriate examples to make each health indicator easy for the reader to understand. We have included practical exercises for some health indicators to help readers understand the underlying concepts.

Licochalcone C Induces Autophagy in Gefitinib-sensitive or-resistant Human Non-small Cell Lung Cancer Cells (Gefitinib-민감성 또는 내성 비소세포폐암 세포에서 Licochalcone C에 의한 자가포식 유도)

  • Oh, Ha-Na;Yoon, Goo;Chae, Jung-Il;Shim, Jung-Hyun
    • Journal of Life Science
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    • v.29 no.12
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    • pp.1305-1313
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    • 2019
  • Licochalcone (LC), isolated from the roots of Glycyrrhiza inflata has multiple pharmacological effects including anti-inflammatory and anti-tumor activities. To date, Licochalcone C (LCC) has induced apoptosis and inhibited cell proliferation in oral and bladder cancer cells, but lung cancer has not yet been studied. In addition, no study reported LCC-induced autophagy in cancer until now. The present study was designed to investigate the effect of LCC on gefitinib-sensitive and -resistant lung cancer cells and elucidate the mechanism of its action. The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay data showed that LCC significantly inhibited cell viability in non-small cell lung cancer (NSCLC) HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) cell lines. Interestingly, Annexin V/7-aminoactinomycin D double staining and cell cycle analysis showed an apoptosis rate within about 20% at the highest concentration of LCC. LCC induced G2/M arrest by reducing the expression of the cell cycle G2/M related proteins cyclin B1 and cdc2 in NSCLC cell lines. Treatment of LCC also induced autophagy by increasing the expression of the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) and the protein autophagy-related gene 5 involved in the autophagy process. In addition, LCC increased the production of reactive oxygen species (ROS), and the cell viability was partially restored by treatment with the ROS inhibitor N-acetyl-L-cysteine. In western blotting analysis, the expression of cdc2 was increased and LC3 was decreased by the simultaneous treatment of NAC and LCC. These results indicate that LCC may contribute to anti-tumor effects by inducing ROS-dependent G2/M arrest and autophagy in NSCLC. In conclusion, LCC treatment may be useful as a potential therapeutic agent against NSCLC.

Monitoring Seasonal Influenza Epidemics in Korea through Query Search (인터넷 검색어를 활용한 계절적 유행성 독감 발생 감지)

  • Kwon, Chi-Myung;Hwang, Sung-Won;Jung, Jae-Un
    • Journal of the Korea Society for Simulation
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    • v.23 no.4
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    • pp.31-39
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    • 2014
  • Seasonal influenza epidemics cause 3 to 5 millions severe illness and 250,000 to 500,000 deaths worldwide each year. To prepare better controls on severe influenza epidemics, many studies have been proposed to achieve near real-time surveillance of the spread of influenza. Korea CDC publishes clinical data of influenza epidemics on a weekly basis typically with a 1-2-week reporting lag. To provide faster detection of epidemics, recently approaches using unofficial data such as news reports, social media, and search queries are suggested. Collection of such data is cheap in cost and is realized in near real-time. This research aims to develop regression models for early detecting the outbreak of the seasonal influenza epidemics in Korea with keyword query information provided from the Naver (Korean representative portal site) trend services for PC and mobile device. We selected 20 key words likely to have strong correlations with influenza-like illness (ILI) based on literature review and proposed a logistic regression model and a multiple regression model to predict the outbreak of ILI. With respect of model fitness, the multiple regression model shows better results than logistic regression model. Also we find that a mobile-based regression model is better than PC-based regression model in estimating ILI percentages.

Factors Related to Surgical Site Infections in Patients Undergoing General Surgery (일반외과 환자의 수술부위 감염 관련 요인 분석)

  • Ahn You-Jin;Sohng Kyeong-Yae
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.12 no.1
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    • pp.113-120
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    • 2005
  • Purpose: To identify risk factors for surgical site infections in patients undergoing general surgery, to analyze the prolonged hospital stay and extra cost for antibiotics, and to provide basic data for control of surgical site infections. Method: Surgical site infection was defined using the definition of the CDC and the data were analyzed by $x^2$-test and unpaired t-test. Results: The prevalence of surgical site infections was 9.7%, and it was related to wound class, duration of operation, number of operations, whether the operation was an emergency, trauma, drains, preoperative stays, presence of remote infection during operative period, and previous history of recent surgery. The mean duration for post-operative stay when a surgical site infection occurred was 9.5 days and in 56.9 % of the patients the surgical site infection appeared 7 days after the operation. Post-operative stays for infected patients were 20.3 days longer than that of uninfected patients. The mean cost of antibiotics for infected patients was higher than that for uninfected patients by 561,067 won per person. Conclusion: Surgical site infection results in an increased length of stay and extra-cost, thus, hospitals need to create strategies to reduce nosocomial infections through effective infection surveillance and by considering factors related to surgical site infections.

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Differential Gene Expression after Adenovirus-Mediated p16 Gene Transfer in Human Non-Small Cell Lung Cancer Cells (폐암세포주에서 아데노바이러스 매개 p16 유전자 전달로 인한 유전자 발현의 변화)

  • 박미선;김옥희;박현신;지승완;엄미옥;염태경;강호일
    • Toxicological Research
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    • v.20 no.2
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    • pp.109-116
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    • 2004
  • For the safety evaluation of adenovirus-mediated gene transfer, we investigated differential gene expressions after transfecting adenoviral vector containing p16 tumor suppressor gene (Ad5CMV-p16) into human non-small cell lung cancer cells. In the previous study, we showed adenovirus-mediated $p16^{INK4a}$ gene transfer resulted in significant inhibition of cancer cell growth. We investigated gene expression changes after transfecting Ad5CMV-p16, Ad5CMV (null type, a mock vector) into A549 cells by using cDNA chip and oligonucleotide microarray chip (1200 genes) which carries genes related with signal transduction pathways, cell cycle regulations, oncogenes and tumor suppressor genes. We found that $p16^{INK4a}$ gene transfer down regulated 5 genes (cdc2, cyclin D3, cyclin B, cyclin E, cdk2) among 26 genes involved in cell cycle regulations. Compared with serum-free medium treated cells, Ad5CMV-p16 changed 27 gene expressions, two fold or more on oligonucleotide chip. In addition, Ad5CMV-p16 did not seem to increase the tumorigenicity-related gene expression in A549 cells. Further studies will be needed to investigate the effect of Ad5CMV-p16 on normal human cells and tissues for safety evaluation.

Activation of MAP Kinase during Maturation in Porcine Ooctyes (돼지 미성숙란의 체외배양시 MAP Kinase의 활성)

  • 장규태;박미령;윤창현
    • Korean Journal of Animal Reproduction
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    • v.22 no.3
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    • pp.265-276
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    • 1998
  • In an attempt to evaluate the function of MAP kinase of porcine oocytes and to develop a method of assessment for kinase activity, we used MBP as a substrate to detect the MAP kinase activity of porcine oocytes matured in in vitro. The MAP kinase which had lower activity during the first 20 hours of culture started to show an increased amount of activity at 25 hours at which a collapse in nuclear membrane was induced. Significant (P<0.05) a, pp.ared at 30 hours of being cultured. The gel phosphorylation method, MBP which has been known to be a substrate for kinase such as cdc2 kinase, was phosphorylated at two positions corresponding to ERK 1 (44kDa) and ERK2 (42 kDa) which are known as mammalian MAP kinase. The existence of MARKK and MAP kinase were identified with western blotting at 0 hour culture of immature GV oocytes. The amount of those proteins did not increase during 40 hours of culture, which suggest that the increase of MAP kinase activity was caused by phosphorylaton rather than due to change in protein amount. MAPKK and MAP kinase were shown to be dephosporylated with deactivated at M 1 stage by inhibition of protein synthesis with cycloheximide added at the strat following the cultrue. We have reulsts that indicate the existedence of MAP kinase cascade which was activated simultaneously with start of porcine oocyte maturation (GVBD).

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