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Yeonjoo Jung,
Pora Kim,
Yeonhwa Jung,
Juhee Keum, Soon-Nam Kim,
Yong Soo Choi,
In-Gu Do,
Jinseon Lee,
So-Jung Choi,
Sujin Kim,
Jong-Eun Lee,
Jhingook Kim,
Sanghyuk Lee,
Jaesang Kim
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ABSTRACT: An increasing number of chromosomal aberrations is being identified in solid tumors providing novel biomarkers for various types of cancer and new insights into the mechanisms of carcinogenesis. We applied next generation sequencing technique to analyze the transcriptome of the non-small cell lung carcinoma (NSCLC) cell line H2228 and discovered a fusion transcript composed of multiple exons of ALK (anaplastic lymphoma receptor tyrosine kinase) and PTPN3 (protein tyrosine phosphatase, nonreceptor Type 3). Detailed analysis of the genomic structure revealed that a portion of genomic region encompassing Exons 10 and 11 of ALK has been translocated into the intronic region between Exons 2 and 3 of PTPN3. The key net result appears to be the null mutation of one allele of PTPN3, a gene with tumor suppressor activity. Consistently, ectopic expression of PTPN3 in NSCLC cell lines led to inhibition of colony formation. Our study confirms the utility of next generation sequencing as a tool for the discovery of somatic mutations and has led to the identification of a novel mutation in NSCLC that may be of diagnostic, prognostic, and therapeutic importance.
Genes Chromosomes and Cancer 02/2012; 51(6):590-7. · 3.31 Impact Factor
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Yeonjoo Jung,
Sanghyuk Lee,
Hyung-Seok Choi, Soon-Nam Kim,
Eunyoung Lee,
Youngah Shin,
Jihae Seo,
Bumjin Kim,
Yeonhwa Jung,
Wan Kyu Kim,
Ho-Kyung Chun,
Woo Yong Lee,
Jaesang Kim
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ABSTRACT: Identification of novel biomarkers of cancer is important for improved diagnosis, prognosis, and therapeutic intervention. This study aimed to identify marker genes of colorectal cancer (CRC) by combining bioinformatics analysis of gene expression data and validation experiments using patient samples and to examine the potential connection between validated markers and the established oncogenes such as c-Myc and K-ras.
Publicly available data from GenBank and Oncomine were meta-analyzed leading to 34 candidate marker genes of CRC. Multiple case-matched normal and tumor tissues were examined by RT-PCR for differential expression, and 9 genes were validated as CRC biomarkers. Statistical analyses for correlation with major clinical parameters were carried out, and RNA interference was used to examine connection with major oncogenes.
We show with high confidence that 9 (ECT2, ETV4, DDX21, RAN, S100A11, RPS4X, HSPD1, CKS2, and C9orf140) of the 34 candidate genes are expressed at significantly elevated levels in CRC tissues compared to normal tissues. Furthermore, high-level expression of RPS4X was associated with nonmucinous cancer cell type and that of ECT2 with lack of lymphatic invasion while upregulation of CKS2 was correlated with early tumor stage and lack of family history of CRC. We also demonstrate that RPS4X and DDX21 are regulatory targets of c-Myc and ETV4 is downstream to K-ras signaling.
We have identified multiple novel biomarkers of CRC. Further analyses of their function and connection to signaling pathways may reveal potential value of these biomarkers in diagnosis, prognosis, and treatment of CRC.
Clinical Cancer Research 02/2011; 17(4):700-9. · 7.74 Impact Factor
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Hye-Sung Jeong,
Jin-Ho Shin,
Jung-Yun Choi,
Young-Lim Kim,
Jei-Jun Bae,
Byoung-Guk Kim,
Seung-Rel Ryu, Soon-Nam Kim,
Hong-Ki Min,
Hong-Jin Kim,
Sue-Nie Park
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ABSTRACT: Biopharmaceutical products produced from cell cultures have a potential for viral contamination from cell sources or from adventitious introduction during production. The objective of this study was to assess viral clearance in the production of insect cell-derived recombinant human papillomavirus (HPV)-16 type L1 virus-like particles (VLPs). We selected Japanese encephalitis virus (JEV), bovine viral diarrhea virus (BVDV), and minute virus of mice (MVM) as relevant viruses to achieve the aim of this study. A downstream process for the production of purified HPV-16 L1 VLPs consisted of detergent lysis of harvested cells, sonication, sucrose cushion centrifugation, and cesium chloride (CsCl) equilibrium density centrifugation. The capacity of each purification/treatment step to clear viruses was expressed as reduction factor by measuring the difference in log virus infectivity of sample pools before and after each process. As a result, detergent treatment (0.5% v/v, Nonidet P-40/phosphate-buffered saline) was effective for inactivating enveloped viruses such as JEV and BVDV, but no significant reduction (< 1.0 log(10)) was observed in the non-enveloped MVM. The CsCl equilibrium density centrifugation was fairly effective for separating all three relevant adventitious viruses with different CsCl buoyant density from that of HPV-16 L1 VLPs (JEV, BVDV, and MVM = 4.30, 3.10, > or = 4.40 log(10) reductions). Given the study conditions we used, overall cumulative reduction factors for clearance of JEV, BVDV, and MVM were > or = 10.50, > or = 9.20, and > or = 6.40 log(10) in 150 ml of starting cell cultures, respectively.
Biologicals 01/2007; 34(4):273-9. · 1.70 Impact Factor
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ABSTRACT: Plasma-derived products are produced from plasma via fractionation and chromatography techniques, but can also be produced by other methods. In the performance of nucleic acid amplification tests (NAT) with plasma-derived products, it is necessary to include an internal control for the monitoring of all procedures. In order to avoid false negative results, we confirmed the usefulness of the bovine viral diarrhoea virus (BVDV) for use as an internal control in the detection of hepatitis C virus (HCV) RNA in plasma-derived products. These products, which were spiked with BVDV, were extracted and then NAT was performed. Specificity and sensitivity were determined via the adjustment of primer concentrations and annealing temperatures. BVDV detection allows for validation in the extraction, reverse transcription, and amplification techniques used for HCV detection in plasma-derived products.
The Journal of Microbiology 03/2006; 44(1):72-6. · 1.10 Impact Factor
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ABSTRACT: Six laboratories consisting of three manufacturers and three national control laboratories participated in a collaborative study to evaluate the suitability of a candidate material to serve as the first Korean National Standard for Antithrombin (AT) concentrate.
The potency of this candidate preparation was determined using the heparin cofactor chromogenic method. The method is described in the Minimum Requirements for Biological Products in Korea and in the European Pharmacopoeia. The candidate was calibrated against the second International Standard for AT concentrate, coded as 96/520.
The participants contributed data from a total of 90 independent assays and the results were accepted as statistically valid when the outcome of the analysis exhibited linear dose-response relationships and intersected at a common point at zero dose in the slope-ratio model. The combined potency estimates were obtained by taking the geometric means of results from all assays at each laboratory, and overall potency estimates were calculated as unweighted geometric means of results from all laboratories. The results were expressed in the form of histograms with 95% confidence intervals.
According to the results of the collaborative study, the candidate preparation showed excellent intra- and inter-laboratory correlations and is judged to be suitable to serve as the Korean National Standard for AT concentrate with the following potency: 51.9 IU/vial (95% confidence intervals=48.24 approximately 55.98 IU/vial).
Thrombosis Research 02/2006; 117(5):591-6. · 2.44 Impact Factor
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ABSTRACT: A collaborative study among five laboratories including three manufacturers and two national control laboratories was carried out to evaluate the suitability of a candidate to serve as a Korean Standard for factor VIII:C concentrate.
Two approaches were attempted to determine the potency of this candidate. The one is a one-stage clotting assay and the other is a chromogenic assay. To achieve acceptable precision and accuracy, the following recommendations by the International Society on Thrombosis and Haemostasis were adopted in the assays, e.g., pre-dilution of samples in factor VIII (FVIII)-deficient plasma, inclusion of 1% albumin in the dilution buffer and calibration against the sixth International Standard for the blood coagulation factor VIII:C concentrate, coded 97/616.
The data collected within each laboratory and among laboratories for both assays employed here were in good agreements in the calibration of the candidate preparation against the International Standard. The overall potencies by the one-stage clotting assay and the chromogenic assay, however, showed recognizable differences between them. Each differed from each other in that the potency obtained from chromogenic assay was approximately 17% lower than that from one-stage clotting assay. The estimated geometric mean value obtained from the one-stage clotting assay was 8.4 international units (IU)/vial and that from the chromogenic assay was 6.7 IU/vial.
Based on the results of this collaborative study, the candidate standard is judged to be suitable to serve as a Korean National Standard for factor VIII:C concentrate.
Thrombosis Research 02/2004; 113(3-4):261-7. · 2.44 Impact Factor
