• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.35-47
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• 2006

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) are well known as the most toxic environmental compound in these days. Many researches are reported that dioxin produces multiple toxic effects, such as endocrine toxicity, reproductive toxicity, immunotoxicity and cancer. In this study, we carried to discover novel evidence for previously unknown gene expression patterns in human exposed to dioxin by using radioactive cDNA microarray. 548 workers who were divided into experimental and control groups according to their urinary Naphthol levels were enrolled in our study. Blood mRNA in human was isolated, and the gene expression profiles were analyzed by cDNA microarray. Gene expression analysis identified 52 genes which exhibited a significant change. In our study, most notably, genes involved in cell cycle, cell proliferation, signal transduction and apoptosis in human exposed to dioxin, such as CCND3, TSHR, and EFRN5, were up-regulated. In the current study, we observed gene expression of people that are exposed to dioxin using radioactive cDNA microarray. Through these results, we suggest when objects are exposed to toxic compounds, such as dioxin, the radioactive cDNA microarray may be using in sensitively detecting of cancerous change.

• 대한핵의학회지
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• 제37권1호
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• pp.43-52
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• 2003

Microarray technology allows the simultaneous analysis of gene expression patterns of thousands of genes, in a systematic fashion, under a similar set of experimental conditions, thus making the data highly comparable. In some cases arrays are used simply as a primary screen loading to downstream molecular characterization of individual gene candidates. In other cases, the goal of expression profiling is to begin to identify complex regulatory networks underlying developmental processes and disease states. Microarrays were originally used with ceil lines or other simple model systems. More recently, microarrays have been used in the analysis of more complex biological tissues including neural systems and the brain. The application of cDNA arrays in neuropsychiatry has lagged behind other fields for a number of reasons. These include a requirement for a large amount of input probe RNA In fluorescent-glass based array systems and the cellular complexity introduced by multicellular brain and neural tissues. An additional factor that impacts the general use of microarrays in neuropsychiatry is the lack of availability of sequenced clone sets from model systems. While human cDNA clones have been widely available, high qualify rat, mouse, and drosophilae, among others are just becoming widely available. A final factor in the application of cDNA microarrays in neuropsychiatry is cost of commercial arrays. As academic microarray facilitates become more commonplace custom made arrays will become more widely available at a lower cost allowing more widespread applications. in summary, microarray technology is rapidly having an impact on many areas of biomedical research. Radioisotope-nylon based microarrays offer alternatives that may in some cases be more sensitive, flexible, inexpensive, and universal as compared to other array formats, such as fluorescent-glass arrays. In some situations of limited RNA or exotic species, radioactive membrane microarrays may be the most practical experimental approach in studying psychiatric and neurodegenerative disorders, and other complex questions in the brain.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 2003년도 추계학술대회 및 총회
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• pp.32.1-32.1
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• 2003

• 한국유전체학회:학술대회논문집
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• 한국유전체학회 2005년도 The 14th Korea Genome Conference
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• pp.65-65
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• 2005

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 2001년도 제40차 추계학술대회 및 총회
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• pp.28.1-28.1
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• 2001

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2001년도 추계학술대회 및 정기총회
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• pp.12-21
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• 2001

To identify genes implicated in the control of pluripotency as well as characteristics of stem cells, we analyzed expression profiles of genes derived from mouse morulas, blastocysts, embryonic stem cells, mesenchymal stem cells, and uterus tissue using cDNA microarray. Comparative analyses of their expression profiles identified putative clones that expressed specifically in specific samples or not in a specific sample. The expression pattern of these condidate clones was analyzed using RT-PCR and non-radioactive in situ hybridization. Functional annotation of these clones on pluripotency and stem cell plasticity is in ongoing. These studies may further our understanding on the nature of the stem cells and molecular mechanisms underlying many facets of mammalian development and differentiation.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 발생공학 국제심포지움 및 학술대회 발표자료집
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• pp.18-24
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• 2001

To identify genes implicated in the control of pluripotency as well as characteristics of stem cells, we analyzed expression profiles of genes derived from mouse morulas, blastocysts, embryonic stem cells, mesenchymal stem cells, and uterus tissue using cDNA microarray. Comparative analyses of their expression profiles identified putative clones that expressed specifically in specific samples or not in a specific sample. The expression pattern of these candidate clones was analyzed using RT-PCR and non-radioactive in situ hybridization. Functional annotation of these clones on pluripotency and stem cell plasticity is in ongoing. These studies may further our understanding on the nature of the stem cells and molecular mechanisms underlying many facets of mammalian development and differentiation.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2001년도 발생공학 국제심포지움 및 학술대회 발표자료집
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• pp.18-24
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• 2001

To identify genes implicated in the control of pluripotency as well as characteristics of stem cells, we analyzed expression profiles of genes derived from mouse morulas, blastocysts, embryonic stem cells, mesenchymal stem cells, and uterus tissue cDNA microarray. Comparative analyses of their expression profiles identified putative clones that expressed specifically in specific samples or not in a specific sample. The expression pattern of these candidate clones was analyzed using RT-PCR and non-radioactive in situ hybridization. Functional annotation of these clones on pluripotency and stem cells and molecular mechanisms underlying many facets of mammalian development and differentiation.

• Radiation Oncology Journal
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• 제21권1호
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• pp.54-65
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• 2003

목적 : 동시에 대량으로 유전자발현 양상을 검사할 수 있는 cDNA microarray 기법을 이용하여 자궁경부암에서 특징적으로 나타나는 유전자발현 양상을 알아보고, 방사선치료 및 방사선 항암화학요법 병용치료시의 유전자발현 변화양상을 파악하고자 하였다. 대상 및 방법 :자궁경부 편평상피암으로 확진된 후 근치목적 방사선치료를 단독으로 시행한 8명과 항암화학요법을 병행한 8명에서 채취한 종양조직을 대상으로 하고, 정상 자궁경부 3례를 대조군으로 하였다 조직 생검은 치료 전과 외부 방사선치료 16.2$\~$27 Gy에 두 번하였다. 항암화학요법을 병용한 경우, 5-FU 1,000 mg/m$^{2}$을 제 1일부터 5일까지 정주하고, clsplatin 60 mg/m$^{2}$을 제 1일에 정주하였다. cDNA microarray는 종양조직에서 추출한 total RNA를 역전사(reverse transcription)방법을 이용하여 (P-33)을 표지한 cDNAS를 제작, nylon membrane에 hybridization하였다. 이후 membrane을 phosphor-imager screens에 옮겨 1$\~$5일 동안 노출시킨 후 이미지를 스캔하였다. 유전자의 발현정도는 각 스팟(spot)들의 방사능 강도로 나타나는데, 각 스팟의 픽셀(pixel)을 Arrayguage를 사용하여 산출한 후 엑셀파일로 저장하였다. 유전자의 발현정도 비교는 원 자료(original data)를 Z-변환을 통해 보정(normalized)한 후 Z-ratio값을 산출하여 시행하였다. 결과 : 대조군에 비해 자궁경부암에서 Z-ratio 2.0 이상으로 유의한 발현증가를 보인 유전자들은 integrin-linked kinase, CDC28 protein kinase 2, Spry 2, ERK 3 등 15개로 주로 세포성장과 증식, 세포주기, 신호전달 등에 관련된 유전자들이었으며, Z-ratio -2.0 이하의 유의한 발현감소는 G protein-coupled receptor kinase 6외 6개였다. 방사선 단독치료를 시행한 후 Z-ratio 2.0 이상 발현이 증가한 것은 cyclic nucleotlde gated channel외 3개의 Expressed sequence tags (EST)들이었고, Z-ratio -2.0 이하의 발현감소를 보인 것들에는 치료전 종양세포에서 발현이 증가되었던 세포성장과 증식, 세포주기, 신호전달 등에 관련된 유전자들이 포함되었다 방사선치료와 항암화학요법을 병용했을 때는 방사선 단독치료에 비하여 세포성장과 증식 및 신호전달 관련 유전자들이 상대적으로 높게 발현되었으며, 이외에도 혈관형성(angiopoietin-2), 면역반응(formyl peptide receptor-like 1), DNA 손상회복에 관련된 유전자(CAMP phosphodiesterase)의 발현은 증가되고 세포고사(death associated protein kinase)에 관련된 유전자는 발현 감소를 보였다. 결론 : 자궁경부암에서분열과 증식 및 신호전달에 관여하는 여러 종류의 유전자들 발현이 동시다발적으로 증가되어 있다는 것과 방사선치료를 시행하면 이들 유전자의 발현이 감소하여 종양세포의 분열과 증식이 저해된다는 것을 확인하였다. 방사선 단독치료와 항암화학요법 병용치료를 비교하면 그 유전자 발현양상이 다르므로 향후 이번연구에서 나타난 유전자들에 대한 추가 연구가 필요하며, 이는 개별화된 맞춤형 치료법을 개발하는데 기초자료로 사용될 수 있을 것으로 기대된다.

• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.62-71
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• 2005

For toxicity model in the kidney, renal cell carcinoma (RCC) is one of the most important model to assess the structural and functional alterations. Most RCCs are sporadic, and environmental agents are suspected to play a role in the etiology of the disease. In this study, we discovered novel evidence for previously unknown gene expression patterns related to progression according to cancer stage in RCC. Four clear cell RCC tissue samples along with five corresponding patient-matched normal kidney tissue samples were obtained from patients undergoing partial or radical nephrectomy. To examine the difference of gene expression profile in clear cell RCC, radioactive cDNA microarrays were used to evaluate changes in the expression of 1,152 genes in a total. Using $^{33}P-labeled$ probes, this method provided highly sensitive gene expression profiles including drug metabolism, and cellular signaling. 29 genes were identified with expression levels that differed by more than 2.0 value of z-ratio, compared with that in control. Whereas expression of 38 genes were decreased by less than-2.0 value of z-ratio. In conclusion, this study has identified 67 gene expression alterations in clear-cell type of RCC. Most notably, genes involved in cell growth were up-regulated in stage I more than stage III whereas genes involved in signal transduction were down-regulated in which both stage I and stage III. The identified alteraions of gene expression will likely give in sight in to clear cell RCC and tumor progression.