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| 1 | Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors显示文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC. | Orsolya Galamb Barbara K Barták Alexandra Kalmár Zsófia B Nagy Krisztina A Szigeti Zsolt Tulassay Peter Igaz Béla Molnár | 2019 | World Journal of Gastroenterology2019，25，34： | 18 |
| 2 | Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon显示文摘Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions are well established biological events which have an important role in not just normal tissue and organ development,but in the pathogenesis of diseases.Increasing evidence has established their presence in the human colon during colorectal carcinogenesis and cancer invasion,chronic inflammation-related fibrosis and in the course of mucosal healing.A large body of evidence supports the role for transforming growth factor-β and its downstream Smad signaling,the phosphatidylinositol 3'-kinase/Akt/mTOR axis,the Ras-mitogen-activated protein kinase/Snail/Slug and FOXC2 pathway,and Hedgehog signaling and microRNAs in the development of colorectal cancers via epithelial-to-mesenchymal transition.C-met and Frizzled-7,among others,seem to be the principle effectors of mesenchymal-to-epithelial transition,hence have a role not just in mucosal regeneration but in the progression of colonic wall fibrosis.Here we discuss a role for these pathways in the initiation and development of the transition events.A better understanding of their induction and regulation may lead to the identification of pathways and factors that could be potent therapeutic targets.The inhibition of epithelial-to-mesenchymal transition using mTOR kinase inhibitors targeting the ATP binding pocket and which inhibit both mTORC1 and mTORC2,RNA aptamers or peptide mimetics,such as a Wnt5A-mimetic,may all be useful in both cancer treatment and delaying fibrosis,while the induction of mesenchymal-to-epithelial transition in induced pluripotent stem cells may enhance epithelial healing in the case of severe mucosal damage.The preliminary results of the current studies are promising,but more clinical investigations are needed to develop new and safe therapeutic strategies for diseases of the colon. | Ferenc Sipos Orsolya Galamb | 2012 | World Journal of Gastroenterology2012，18，7： | 13 |
| 3 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 4 | Elevated insulin-like growth factor 1 receptor, hepatocyte growth factor receptor and telomerase protein expression in mild ulcerative colitis显示文摘 | Ferenc Sipos Orsolya Galamb László Herszényi Béla Molnár Norbert Solymosi Tamás Zágoni Lajos Berczi Zsolt Tulassay | 2008 | Scandinavian Journal of Gastroenterology2008，，3： | 2 |
| 5 | mRNA expression, functional profiling and multivariate classification of colon biopsy specimen by cDNA overall glass microarray显示文摘AIM: To understand the local pathophysiological altera- tions and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic dis- eases. METHODS: Total RNA was extracted from frozen biop- sies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microar- ray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinomas (CRCs), and 6 inflammatory bowel diseases (IBDs). Multivariate statistical and cell functional analyses were performed. Real-time RT-PCR and immunohistochemistry were used for validation. RESULTS: Discriminant analysis of selected genes, could correctly reclassify all 22 samples using 4 parameters (heat shock transcription factor-1, bystin-like, calgranu- lin-A, TRAIL receptor 3). IBD samples were characterized by overregulated chemokine (C-X-C motif) ligand 13, replication protein A1, E74-like factor 2 and downregu- lated TNF receptor-associated factor 6, BCL2-interacting killer genes. In adenomas upregulation of TNF receptor- associated factor 6, replication protein A1, E74-like factor 2 and underexpression of BCL2-associated X protein, cal- granulin-A genes were found. CRC cases had significantly increased epidermal growth factor receptor, topoisomer- ase-1, v-jun, TNF receptor-associated factor 6 and TRAIL receptor 3, and decreased RAD51 and RAD52 DNA repair gene, protein phosphatase-2A and BCL2-interacting killer mRNA levels. Epidermal growth factor receptor RT-PCR and immunohistochemistry, topoisomerase-1 RT-PCRconfirmed the chip results. CONCLUSION: Different histological alterations can be reclassified by functional, multivariate analysis using cDNA microarrays. Further studies with expanded sample number are needed for subclassification of pathological alterations. | Orsolya Galamb Ferenc Sipos Elek Dinya Sandor Spisak Zsolt Tulassay Bela Molnar | 2006 | World Journal of Gastroenterology2006，12，43： | 2 |
| 6 | Evaluation of malignant and benign gastric biopsy specimens by mRNA expression profile and multivariate statistical methods 显示文摘 | Galamb O Sipos F Molnar B | 2007 | Cytometry B Clinical Cytometry2007，72，5： | 1 |
| 7 | The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer显示文摘 | Toth K Galamb O Spisak S | 2011 | Pathol Oncol Res2011，17，： | 1 |
| 8 | Matrix Metalloproteinase-9 Expression in the Normal Mucosa–Adenoma–Dysplasia–Adenocarcinoma Sequence of the Colon显示文摘 | László Herszényi Ferenc Sipos Orsolya Galamb Norbert Solymosi István Hritz Pál Miheller Lajos Berczi Béla Molnár Zsolt Tulassay | 2008 | Pathology & Oncology Research2008，，1： | 1 |
| 9 | Uterine anomalies in women with recurrent pregnancy loss 显示文摘 | Galamb A Pethi~ B Fekete D | 2015 | Orv Hetil2015，156，27： | 1 |
| 10 | Promoter hypermethylation- related reduced somatostatin production promotes uncontrolled cell proliferation in colorectal cancer 显示文摘 | Leiszter K Sipos F Galamb O | 2015 | PLoS One2015，10，01： | 1 |
| 11 | Matrix metalloproteinase-9 expression in the normal mucosa-adenoma-dysplasia-adenocarcinoma sequence of the colon 显示文摘 | Herszenyi L Sipos F Galamb O | 2005 | Pathol Oncol Res2005，14，1： | 1 |
| 12 | Stable alkylcohalt carbonyls:cobalt tetracarbonyl compounds显示文摘 | GALAMB V P(A)LYI G CSER F | 1981 | J Organomet Chem1981，209，2： | 1 |
| 13 | η1-andη3-benzylcobalt earbonyls显示文摘 | GALAMB V P(A)LYI G | 1982 | J Chem Soc:Chem Commun1982，，9： | 1 |
| 14 | Functional mRNA expression analysis and classification of colonic biopsy samples using overall cDNA microarray technique显示文摘 | Galamb O Sipos F Dinya E | 2008 | Orv Hetil2008，149，5： | 1 |
| 15 | The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer显示文摘 | T6thK Galamb O Spisdk S | 2011 | Pathoi Oncol Res2011，17，3： | 1 |
| 16 | Molecular pathogenesis of Helicobacter pylori infection:the role of bacterial virulence factors显示文摘 | Molnar B Galamb O Sipos F et a1 | 2010 | Dig Dis2010，28，45： | 1 |
| 17 | Uterine anomalies in women with recurrent pregnancy loss显示文摘 | Galamb PethB Fekete D | 2015 | Orv Hetil2015，156，27： | 1 |
| 18 | DNA chips for gene expression analysis and their application in diagnostics 显示文摘 | Galamb O Molnar B Tulassay Z | 2003 | Orv Hetil2003，144，1： | 1 |
| 19 | The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer显示文摘 | Toth K Galamb O Spiscik S | 2011 | Pathol Oncol Res2011，17，3： | 1 |
| 20 | Potential biomarkers of colorecta: adenoma-dysplasia-careinoma progression: mRNA expression profiling and in situ protein detection on TMAs reveal 15 sequentially upregulated and 2 downregulated genes 显示文摘 | Galamb O Sipos F Spisak S | 2009 | Cell 0neo12009，31，1： | 1 |
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