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Long Non-coding RNAs are Differentially Expressed in Hepatocellular Carcinoma Cell Lines with Differing Metastatic Potential

  • Fang, Ting-Ting;Sun, Xiao-Jing;Chen, Jie;Zhao, Yan;Sun, Rui-Xia;Ren, Ning;Liu, Bin-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10513-10524
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    • 2015
  • Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

Prognostic Value of CD44 Variant exon 6 Expression in Non-Small Cell Lung Cancer: a Meta-analysis

  • Zhao, Shuang;He, Jin-Lan;Qiu, Zhi-Xin;Chen, Nian-Yong;Luo, Zhuang;Chen, Bo-Jiang;Li, Wei-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6761-6766
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    • 2014
  • Background: CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta-analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. Materials and Methods: Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to estimate the effects. Results: A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95%CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95%CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95%CI=1.93-4.72, p<0.00001). Conclusions: Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.

Sperm-Associated Antigen 9 is a Promising marker for Early Diagnosis of Endometrial Cancer

  • Baser, Eralp;Togrul, Cihan;Ozgu, Emre;Ayhan, Sevgi;Caglar, Mete;Erkaya, Salim;Gungor, Tayfun
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7635-7638
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    • 2013
  • Background: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. Materials and Methods: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. Results: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was $58.7{\pm}1.1$. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). Conclusions: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.

Scutellaria Extract Decreases the Proportion of Side Population Cells in a Myeloma Cell Line by Down-regulating the Expression of ABCG2 Protein

  • Lin, Mei-Gui;Liu, Li-Ping;Li, Chen-Yin;Zhang, Meng;Chen, Yuling;Qin, Jian;Gu, Yue-Yu;Li, Zhi;Wu, Xin-Lin;Mo, Sui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7179-7186
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    • 2013
  • Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

Growth Factor Receptor Expression on Brain Tumor Cell Lines : Preliminary Study for in vitro and in vivo Experiments of Immunotoxin Therapy (뇌종양세포주에서의 성장인자수용체의 발현 : 면역독소 치료의 연구를 위한 예비실험)

  • im, Ki-Uk;Ni, Hsiao-Tzu;Low, Walter C.;Hall, Walter A.
    • Journal of Korean Neurosurgical Society
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    • v.29 no.6
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    • pp.731-737
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    • 2000
  • Objective : Growth factor receptors on the tumor cells are known to be expressed highly allowing the tumor cells to bind growth factors to stimulate cellular division. Immunotoxin therapy is one of the novel approaches to the primary malignant brain tumor, and expression of cell-surface receptor is essential for the immunotoxin to have specific anti-tumor activity. Despite promising cytotoxic activity of immunotoxin, tumor responses are not curative on clinical trials, and additional studies are needed regarding various factors influencing the efficacy of the immunotoxin. The purpose of this study is to detect the expression of various growth factor receptors on brain tumor cell lines which are going to be used in these studies. Materials and Methods : The authors detected transferrin receptor(TR), insulin-like growth factor-1 receptor(IGF-1R), and interleukin-4 receptor(IL-4R) on medulloblastoma cell line(Daoy) and glioblastoma cell lines(U373 MG and T98 G) by flow cytometric analysis. Results : TR was expressed on Daoy, U373 MG, and T98 G. IGF-1R was expressed on Daoy and U373 MG, but not on T98 G. IL-4R was expressed on all cell lines tested. Conclusion : The transferrin and interleukin-4 receptors might be good targets for immunotoxin therapy. The results should be considered in additional in vitro and in vivo studies regarding immunotoxin and in establishing the proper treatment model of the immunotoxin therapy including selection of the adequate immunotoxin.

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Estimated Soft Information based Most Probable Classification Scheme for Sorting Metal Scraps with Laser-induced Breakdown Spectroscopy (레이저유도 플라즈마 분광법을 이용한 폐금속 분류를 위한 추정 연성정보 기반의 최빈 분류 기술)

  • Kim, Eden;Jang, Hyemin;Shin, Sungho;Jeong, Sungho;Hwang, Euiseok
    • Resources Recycling
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    • v.27 no.1
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    • pp.84-91
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    • 2018
  • In this study, a novel soft information based most probable classification scheme is proposed for sorting recyclable metal alloys with laser induced breakdown spectroscopy (LIBS). Regression analysis with LIBS captured spectrums for estimating concentrations of common elements can be efficient for classifying unknown arbitrary metal alloys, even when that particular alloy is not included for training. Therefore, partial least square regression (PLSR) is employed in the proposed scheme, where spectrums of the certified reference materials (CRMs) are used for training. With the PLSR model, the concentrations of the test spectrum are estimated independently and are compared to those of CRMs for finding out the most probable class. Then, joint soft information can be obtained by assuming multi-variate normal (MVN) distribution, which enables to account the probability measure or a prior information and improves classification performance. For evaluating the proposed schemes, MVN soft information is evaluated based on PLSR of LIBS captured spectrums of 9 metal CRMs, and tested for classifying unknown metal alloys. Furthermore, the likelihood is evaluated with the radar chart to effectively visualize and search the most probable class among the candidates. By the leave-one-out cross validation tests, the proposed scheme is not only showing improved classification accuracies but also helpful for adaptive post-processing to correct the mis-classifications.

Development of the Novel Cosmetics Impregnation Material and Study on Makeup W/O Emulsions using It (새로운 화장료 함침재의 개발과 이를 활용한 메이크업 유중수형 에멀전에 관한 연구)

  • Kang, Sungsoo;Kim, Hyeon Jeong;Oh, Se Woong;Park, Sang Wook;Kim, Kyung Seob
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.1
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    • pp.27-33
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    • 2017
  • Up to now, better convenience and portability were important factors in the development of the cosmetics and achieved by immersing low viscosity makeup water-in-oil (W/O) emulsion into the impregnation material. Conventionally, polyurethane sponges having porous network structures and hard textures have been dominantly used. It has an advantage of easy to manufacture because of its good impregnation property due to its structural characteristics. However, it releases emulsion too much at first use, and shows unexpected dramatic decline during the period of usage. In this study, we studied on makeup W/O emulsion with various features and developed the new foaming sponge, which showed excellent formability and proper absorption and discharge ability of cosmetic composition through the combination of natural rubber (NR) and styrene butadiene rubber (SBR). This impregnation material is characterized by the softness of elasticity like a rubber, high elongation and uniform output. We confirmed that this material can be used to develop makeup products using various oils depending on polarity and controlling the viscosity of the makeup W/O emulsion. Thus, it is concluded that these results provide valuable information in developing new cosmetics impregnation materials.

A study on the Dioxin behavior in the process of representative pyrolysis/gasfication/melting plant (대표적인 열분해가스화 용융시설의 공정별 다이옥신 배출거동에 관한 연구)

  • Shin, Chan-Ki;Shin, Dae-Yun
    • Journal of environmental and Sanitary engineering
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    • v.22 no.1 s.63
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    • pp.1-16
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    • 2007
  • The incineration process has commonly used for wastes amount reduction and thermal treatments of pollutants as the technologies accumulated. However, the process is getting negative public images owing to matter of hazardous pollutants emission. Specially dioxins became a main issue and is mostly emitted from municipal solid wastes incineration. In this reason, pyrolysis/gasfication/melting process is presented as a alternative of incineration process. The pyrolysis/gasfication/melting process, a novel technology, is middle of verification of commercial plant and development of technologies in Korea. But the survey about the pollutant emission from the process, and background data in these facilities is necessary. So in this survey, it Is investigated that the behavior of dioxins in three pyrolysis/gasfication/melting plant (S, T, P) of pilot scale. In case of S plant, concentration of dioxins shows high at latter part of cogenerated boiler and stack which are operate on low temperature conditions than a latter parts of pyrolysis and melting furnace which are operate on high temperature condition. Concentration of gas phage dioxins had increased after combusted gas passed cogenerated boiler and this is attributed to react of precursor materials such as chlorobenzene and chlorophenol. Concentration of dioxins in T plant showed lower levels at latter part of cooling equipment which are operate with water spray type on low temperature conditions than a latter parts of gasfied melting furnace which are operate on high temperature condition. Removal efficiency of dioxins at gas treatment equipment was 78.8 %. Concentration of dioxins in P plant was low at latter part of SDA/BF which is operate at low temperature conditions than a latter parts of pyrolysis gasfied chamber which are operate at high temperature condition. Removal efficiency of dioxins of SDA/BF was 85.9 % and therefore, it showed high efficiency at those of stoker type incineration facility. However, concentration of dioxins which emitted at high temperature condition were low in three facilities and satisfied present standard emission level of dioxins. To consider the distribution ratio of dioxins, Particulate phase dioxins at S and P plants showed similar ratio with which shows in current stoker type for middle scale domestic waste incineration facility. It is necessary to continuos monitoring the ratio of distribution of dioxins in T plant in because ratio of gas phage dioxins showed high.

A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice

  • Saba, Evelyn;Lee, Yuan Yee;Kim, Minki;Hyun, Sun-Hee;Park, Chae-Kyu;Son, Eunjung;Kim, Dong-Seon;Kim, Sung-Dae;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.833-842
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    • 2020
  • Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer

  • Im, Jung Ho;Seong, Jinsil;Lee, Jeongshim;Kim, Yong Bae;Lee, Ik Jae;Park, Jun Sung;Yoon, Dong Sup;Kim, Kyung Sik;Lee, Woo Jung
    • Radiation Oncology Journal
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    • v.32 no.1
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    • pp.7-13
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    • 2014
  • Purpose: To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. Materials and Methods: Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). Results: The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (${\geq}50$ Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). Conclusion: In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.