• Title/Summary/Keyword: Tissue microarray

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Gene Expression Profiling of Non-Hodgkin Lymphomas

  • Zekri, Abdel-Rahman Nabawy;Hassan, Zeinab Korany;Bahnassy, Abeer Ahmed;Eldahshan, Dina Hassan;El-Rouby, Mahmoud Nour Eldin;Kamel, Mahmoud Mohamed;Hafez, Mohamed Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4393-4398
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    • 2013
  • Background: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach. Materials and Methods: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer. Results: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3. Conclusions: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development.

Application of Bioinformatics for the Functional Genomics Analysis of Prostate Cancer Therapy

  • Mousses, Spyro
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2000.11a
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    • pp.74-82
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    • 2000
  • Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

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cDNA Microarray Analysis of the Gene Expression Profile of Swine Muscle

  • Kim, Chul Wook;Chang, Kyu Tae;Hong, Yeon Hee;Jung, Won Yong;Kwon, Eun Jung;Cho, Kwang Keun;Chung, Ki Hwa;Kim, Byeong Woo;Lee, Jung Gyu;Yeo, Jung Sou;Kang, Yang Su;Joo, Young Kuk
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.8
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    • pp.1080-1087
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    • 2005
  • By screening specific genes related to the muscle growth of swine using cDNA microarray technology, a total of 5 novel genes (GF (growth factor) I, II, III, IV and V) were identified. Results of southern blotting to investigate the number of copies of these genes in the genome of swine indicated that GF I, GF III, and GF V existed as one copy and GF II, and GF IV existed as more than two copies. It was suggested that there are many isoforms of these genes in the genome of swine. Also, results of northern blotting to investigate whether these genes were expressed in grown muscle, using GF I, III, and V indicated that all the genes were much more expressed in the muscle of swine with body weight of 90 kg. Expression patterns of these genes in other organs, namely muscle and propagation and fat tissues, were investigated by extracting RNA from the tissues. These genes were not expressed in the propagation and fat tissues, but were expressed in the muscle tissue. To determine the mechanism of muscle growth, further studies should be preceded using the 3 specific genes related to muscle growth, that is GF I, III, and V.

Dysregulation of Cannabinoid CB1 Receptor Expression in Subcutaneous Adipocytes of Obese Individuals

  • Lee, Yong-Ho;Tharp, William G.;Dixon, Anne E.;Spaulding, Laurie;Trost, Susanne;Nair, Saraswathy;Permana, Paska A.;Pratley, Ridhard E.
    • Animal cells and systems
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    • v.13 no.4
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    • pp.371-379
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    • 2009
  • The endocannabinoid system (ECS) plays a key role in the regulation of appetite, body weight and metabolism. We undertook the present study to further clarify the regulation of the cannabinoid CB1 receptor (CB1, CNR1) in human adipose tissue in obesity. CB1 receptor mRNA expression was ~1.6-fold (p<0.004) and 1.9-fold higher (P<0.05) in subcutaneous adipocytes from obese compared to non-obese subjects in microarray and quantitative real-time PCR studies, respectively. Higher CB1 receptor mRNA expression levels in both adipose tissue (~1.2 fold, P<0.05) and adipocytes (~2 fold, P<0.01) were observed in samples from visceral compared to subcutaneous depots collected from 22 obese individuals. Immunofluorescence confocal microscopy demonstrated the presence of CB1 receptor on adipocytes and also adipose tissue macrophages. These data indicate that adipocyte CB1 receptor is up-regulated in human obesity and visceral adipose tissue and also suggest a potential role for the ECS in modulating immune/inflammation as well as fat metabolism in adipose tissue.

Microarray-Based Gene Expression Profiling to Elucidate the Effectiveness of Woowhangchongshim-won on ICH Model in Rats (Microarray 분석법 활용을 통한 뇌출혈 흰쥐에서의 우황청심원 효능 평가)

  • Kim, Hyung-Woo;Cho, Su-Jin;Kim, Bu-Yeo;Jeong, Byeong-Han;Bong, Sung-Jeon;Kim, Yong-Seong;Lee, Jang-Sik;Kwon, Jeong-Nam;Kim, Young-Kyun;Cho, Su-In
    • The Korea Journal of Herbology
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    • v.22 no.4
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    • pp.253-260
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    • 2007
  • Objectives : Intracerebral hemorrhage (ICH) is characterized by breakdown of blood vessels within the brain parenchyma. Fundamental therapeutic strategies for ICH, particularly those aimed at neuroprotection, have to be established. So in this experiment, the effects of Woowhangchongshim-won, a traditional prescription formula for treating Cerebral Apoplexy in Asian countries, were investigated. Methods : After intraperitoneal injection of chloralhydrate, rats were placed in a stereotaxic frame. ICH was induced by injection of 1 U collagenase type IV and drug was administered orally for 10 days. The molecular profile of cerebral hemorrhage in rat brain tissue was measured using micro array technique to identify up- or down- regulated genes in brain tissue. These genes induced by brain damage were mainly concerned with general metabolic process such as primary metabolic process, cellular metabolic process, macromolecule metabolic process, and biosynthetic process. Results : The number of genes increased in control and not-changed in experiment was 374, and decreased in control and not-changed in experiment was 527. We are concerned with genes that can be recovered by treatment with medicine, it is especially interesting to above types of genes. Conclusions : Upon medicine treatment to the rat having cerebral hemorrhage, expressions of some genes were restored to normal level. Further analysis using protein interaction database identified some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future.

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Effect of Banhahoobak-tang (Banxiahoupo-tang) Extract (BHTe) on Psychological Stress (반하후박탕(半夏厚朴湯)이 생쥐의 심리적 스트레스에 미치는 영향과 유전자 분석)

  • Choi, Geum-Ae;Cho, Su-In;Kim, Kyeong-Su;Choi, Chang-Won;Wei, Tung-Shuen;Yang, Seung-Joung;Park, Soo-Yeon;Kim, Kyeong-Ok
    • Journal of Oriental Neuropsychiatry
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    • v.26 no.2
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    • pp.117-130
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    • 2015
  • Objectives: Banhahoobak-tang has been used to treat plum-pit qi, chest and hypochondriac distension, moist or greasy tongue coat, and wiry slow or wiry slippery pulse. It might be used to control coughing and vomiting. We observed that Banhahoobak-tang extract (BHTe) had anti-psychological stress effect. The objective of this study was to determine the effect of BHTe on restoring the transcriptional regulation of genes related to psychological stress. Methods: After giving psychological stress to mice, BHTe was orally administered at 100 mg/kg/day for five days. After extracting whole brain tissue from the mice, the gene expression changes were determined by microarray. Transcription factor binding site (TFBS) analysis showed up- and down-regulated genes related to psychological stress were protected by BHTe and segregated according to the structure of TFBS. We performed text based Pubmed search to select significant target genes involved in psychological stress affected by BHTe. Results: 1. Serum corticosterone level was decreased in the BHTe administered group, although the psychological stress was increased. 2. The BHTe administered group had no significant change in noradrenaline content in brain tissue, but the psychological stress group had decreased level. 3. The BHTe administered group had increased time of staying at open-arm than the psychological stress group. 4. Microarray revealed that TANK and RARA genes were up-regulated genes while AES, CDC42, FOS, NCL, and PVR were down-regulated genes by psychological stress but restored by BHTe.

Analysis of the Gene Expression by Laser Capture Microdissection (III) -Microarray Analysis of the Gene Expression at the Mouse Uterine Luminal Epithelium of the Implantation Sites during Apposition Period- (Laser Capture Microdissection을 이용한 유전자 발현 연구 (III) -생쥐 착상 부위 자궁 내강상피 조직에서 배아 병치 기간 동안 일어나는 유전자 발현에 관한 Microarray 분석-)

  • Yoon, Se-Jin;Jeon, Eun-Hyun;Park, Chang-Eun;Ko, Jung-Jae;Choi, Dong-Hee;Cha, Kwang-Yul;Kim, Se-Nyun;Lee, Kyung-Ah
    • Clinical and Experimental Reproductive Medicine
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    • v.29 no.4
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    • pp.323-335
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    • 2002
  • Object: The present study was accomplished to obtain a gene expression profile of the luminal epithelium during embryo apposition in comparison of implantation (1M) and interimplantation (INTER) sites. Material and Method: The mouse uterine luminal epithelium from IM and INTER sites were sampled on day 4.5 (Day of vaginal plug = day 0.5) by Laser Captured Microdissection (LCM). RNA was extracted from LCM captured epithelium, amplified, labeled and hybridized to microarrays. Results from microarray hybridization were analyzed by Significance Analysis of Microarrays (SAM) method. Differential expression of some genes was confirmed by LCM followed by RT-PCR. Results: Comparison of IM and INTER sites by SAM identified 73 genes most highly ranked at IM, while 13 genes at the INTER sites, within the estimated false discovery rate (FDR) of 0.163. Among 73 genes at IM, 20 were EST/unknown function, and the remain 53 were categorized to the structural, cell cycle, gene/protein expression, immune reaction, invasion, metabolism, oxidative stress, and signal transduction. Of the 24 structural genes, 14 were related especially to extracellular matrix and tissue remodeling. Meanwhile, among 13 genes up-regulated at INTER, 8 genes were EST/unknown function, and the rest 5 were related to metabolism, signal transduction, and gene/protein expression. Among these 58 (53+5) genes with known functions, 13 genes (22.4%) were related with $Ca^{2+}$ for their function. Conclusions: Results of the present study suggest that 1) active tissue remodeling is occurring at the IM sites during embryo apposition, 2) the INTER sites are relatively quiescent than IM sites, and 3) the $Ca^{2+}$ may be a crucial for apposition. Search for human homologue of those genes expressed in the mouse luminal epithelium during apposition will help to understand the implantation process and/or implantation failure in humans.

Analysis of Gene Expression in Helicobacter pylori-associated Nodular Gastritis in Children Using Microarray (소아의 Helicobacter pylori 감염에 의한 결절성 위염의 유전자 발현 양상 분석)

  • Yang, Hye-Ran;Ko, Jae-Sung;Seo, Jeong-Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.13 no.1
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    • pp.7-22
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    • 2010
  • Purpose: Nodular gastritis is a characteristic finding of Helicobacter pylori infection in children. The aim of this study was to evaluate the difference in gene expression in the gastric mucosa of H. pylori-infected and non-infected children, and to analyze the difference in gene expression using cDNA microarray analysis of nodular gastritis caused by H. pylori infection. Methods: Twelve children (6 boys and 6 girls; mean age 9.8 years) who underwent upper gastrointestinal endoscopy and biopsy at Seoul National University Bundang Hospital were included in the study. The subjects were divided into three groups according to the presence of H. pylori infection and nodular gastritis on endoscopic examination. Gastric mucosa tissue was kept at $-70^{\circ}C$ and RNA was extracted to perform cDNA microarray analysis in each patient. Results: cDNA microarray analysis in children revealed a clear distinction between H. pylori-infected and non-infected gastric mucosa. Specifically, 182 over-expressed genes and 29 under-expressed genes were identified in H. pylori-infected gastric mucosa compared to non-infected mucosa. H. pylori-infected nodular gastritis revealed different gene expression patterns from H. pylori-infected normal gastric mucosa; five genes were over-expressed and five genes were under-expressed. Conclusion: In the presence of H. pylori infection, gastric mucosa shows distinct differences in gene expression, and nodular gastritis with H. pylori infection in children may be associated with over- or under-expression of some genes. Further studies are required to clarify the host response and the pathogenesis of nodular gastritis in children.

Effects of Angelicae Gigantis Radix on Gene Expression of Ovarian Tissue in Polycystic Ovary Syndrome Rats (당귀(當歸)가 다낭성난소증후군이 유발된 흰쥐 난소조직의 유전자 발현에 미치는 영향)

  • Ryu, Ki-Jun;Cho, Sung-Hee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.24 no.3
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    • pp.28-47
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    • 2011
  • Objectives: This study was performed to investigate the effects of Angelicae gigantis Radix (AGR) which is one of the most useful herbal-drug to treat patients with Polycystic Ovary Syndrome (PCOS) in Oriental medicine on gene expression of ovary tissue. Methods: The effects of AGR on gene expression of ovary tissue resected from PCOS induced rats using single injection of $\ss$-Estradiol 17-valerate (EV) was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 2,812 genes were up-regulated or down-regulated, 1,421 genes were up-regulated, 1,391 genes were down-regulated by induction of PCOS. Up-regulated genes were mainly involved in biological function such as cell signalling pathways and inflammatory response. Expression levels of 1,442 genes were restored to those of naive animals by administration of AGR. 558 genes were restored to those of naive animals, which were lowered by induction of PCOS. 884 genes were lowered to naive levels, which were elevated by induction of PCOS. The functions of restored genes were partially involved in the restoration of expression levels, which were changed by induction of PCOS. Especially, up-regulated gene by induction of PCOS were mainly involved in these changes. These results mean restorative effects of AGR on damaged functions by induction of PCOS. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as IRS2, MCM10, ORC2L related in up-regulated genes, CTBP2, CD44, RHOA, related in down-regulated genes that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: Restored genes by AGR were thought to have common pathways related in regulation of gene expressions. Especially, genes in restored expression levels by AGR, which were up-regulated by induction of PCOS, were regulated by 9 of common transcription factors, genes in restored expression levels by AGR, which were down-regulated by induction of PCOS, were involved in 25 of common transcription factors.

Effects of Pinelliae Rhizoma on Gene Expression of Lung Tissue from Asthma induced Mice (반하가 천식이 유발된 생쥐 폐조직의 유전자 발현에 미치는 영향)

  • Lee, Myung-Jin;Kim, Jong-Han;Choi, Jeong-Hwa;Park, Su-Yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.21 no.3
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    • pp.36-51
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    • 2008
  • Objective : This study investigated the effects of PR(Pinelliae Rhizoma) on gene expression of lung tissue resected from asthma induced mice using intra-nasal instillation. Methods : Gene expression levels were measured using a microarray technique, and a functional analysis on these genes was conducted. Results : A total of 3270 genes were up-regulated or down-regulated, 860 genes which were lowered by induction of asthma were restored to those of naive animals, Furthermore hand, 1235 genes were lowered to normal levels, which were elevated by induction of asthma. Most of changed genes were involved in signalling pathways. Genes in which expression levels were restored by oral administration of PR were involved in MAPK pathway, focal adhesion, and regulation of actin cytoskeleton etc. Genes of which expression levels were lowered by oral administration of PR were involved in rhodopsin-like receptor activity, zinc ion binding and ATP binding. These genes were also involved in neuroactive ligand receptor interaction, the JAK-STAT signaling pathway and also the T-cell receptor signaling pathway. Conclusion : These results demonstrate the strong possibility that the mechanisms of PR on asthma are involved in neuroactive ligand receptor interaction pathway or related molecules.

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