European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 2014
Early molecular detection of the colorectal dysplasia-carcinoma transition may augment the accura... more Early molecular detection of the colorectal dysplasia-carcinoma transition may augment the accuracy of diagnosis in case of biopsy orientation errors. The combination of high-throughput microarray-based biomarker screening with tissue microarray-based prospective protein biomarker expression analysis could represent an additional test in routine automated diagnostic procedures. Our aim was to test and select protein markers to identify protein expression profile alterations, focusing on the dysplasia-carcinoma transition in sporadic colorectal tumors. Dysplasia-carcinoma transition-specific transcript sets were previously identified using HGU133plus2 microarrays and Taqman RT-PCR cards. Here, 26 potential dysplasia-carcinoma transition-specific markers were tested by immunohistochemistry at the protein level using tissue microarrays in a total of 168 independent colonic biopsy samples. A set of 26 transcripts [including matrix metalloproteinase-3 (MMP3) and chemokine (C-X-C motif) l...
Background and aims: Though histopathology is still the gold standard for differentiating stages ... more Background and aims: Though histopathology is still the gold standard for differentiating stages of colorectal disease progression, the cut slide may represent only a fragment of the whole sample and disease features, such as dysplastic areas of flat adenomas, may remain hidden due to inappropriate sampling or tissue orientation. The early molecular detection of the colorectal dysplasia-carcinoma transition may enhance the strenght of diagnosis from colonic biopsies. Using high-throughput microarray-based biomarker screening low cost diagnostic array real-time PCR panels may be developed. We aimed to determine molecular markers for enhancing the differentiation of high-grade dysplasia from colorectal carcinoma (CRC) and to analyze the applicability of FFPE tissue samples. Material and Methods: Discriminatory transcript set was identified using HGU133plus2 microarrays (Affymetrix Inc.) on 53 biopsy samples (22 CRC, 20 adenoma, 11 normal). For testing the classificatory power of the discriminatory genes, 94 independent biopsies (27 CRC, 29 adenoma, 38 normal) were analyzed on microarrays. Array real-time PCR validation was done on 68 independent samples (24 CRC, 24 adenoma, 20 normal) using LightCycler®480 system (Roche) and RealTime ready assays. Reverse transcription was done using Transcriptor First Strand cDNA Synthesis Kit (Roche). For testing the applicability of FFPE tissues, total RNA was isolated from 10um-thick slides of 5 CRC and 2 adjacent normal samples using High Pure RNA Paraffin Kit (Roche). The same cDNA synthesis and real-time PCR conditions were applied as in case of fresh frozen samples. Results: A set of 11 transcripts was determined which could correctly discriminate between not only the normal, adenoma and CRC samples, but between high-grade dysplastic adenoma and CRC samples by 100% sensitivity and 88.9% specificity. The discriminatory power of the marker set was proved to be high on independent fresh frozen biopsy samples in both microarray and RT-PCR analyses. 95.6% of original and 94.1% of cross-validated samples were correctly classified in discriminant analysis. According to the RT-PCR results for the set of 11 markers, tumorous and normal FFPE tissue samples could be distinguished by 100% sensitivity and specificity. Conclusion: The identified transcripts could correctly characterize the dysplasia-carcinoma transition in colonic tissue samples, also on a large independent sample set and on FFPE tissue samples. These markers can establish the basis of gene expression based diagnostic classification of colorectal cancer. Diagnostic panels can become part of the automated routine procedure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1155. doi:1538-7445.AM2012-1155
World journal of gastroenterology : WJG, Jan 28, 2015
To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived gro... more To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor (HGFR)-expressing cells in active ulcerative colitis (UC). On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected. After preparing tissue microarrays and blood smears HGFR, caudal type homeobox 2 (CDX2), prominin-1 (CD133) and Musashi-1 conventional and double fluorescent immunolabelings were performed. Immunostained samples were digitalized using high-resolution Mirax Desk instrument, and analyzed with the Mirax TMA Module software. For semiquantitative counting of immunopositive lamina propria (LP) cells 5 fields of view were counted at magnification × 200 in each sample core, then mean ± SD were determined. In case of peripheral blood smears, 30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells ...
Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA... more Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples s...
World journal of gastroenterology : WJG, Jan 14, 2009
Peutz-Jeghers syndrome (PJS), a rare autosomal dominant inherited disorder, is characterized by h... more Peutz-Jeghers syndrome (PJS), a rare autosomal dominant inherited disorder, is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. Patients with this syndrome have a predisposition to a variety of cancers in multiple organs. Mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a major cause of PJS. Here we present the clinical and molecular findings of two unrelated Thai individuals with PJS. Mutation analysis by Polymerase Chain Reaction-sequencing of the entire coding region of STK11 revealed two potentially pathogenic mutations. One harbored a single nucleotide deletion (c.182delG) in exon 1 resulting in a frameshift leading to premature termination at codon 63 (p.Gly61AlafsX63). The other carried an in-frame 9-base-pair (bp) deletion in exon 7, c.907_915del9 (p.Ile303_Gln305del). Both deletions were de novo and have never been previously described. This study has expanded the genotypic spectrum of the STK11 gene.
The pathogenesis of inflammatory bowel diseases is still unknown, but is accessible from several ... more The pathogenesis of inflammatory bowel diseases is still unknown, but is accessible from several ways. One possibility is the immunohistochemical analysis of cellular changes in the intestinal mucosa. The increased epithelial cell turnover is connected with false immunological pathways in the subepithelial layer. Behind these disturbances which can lead to chronic remitting inflammatory processes the imbalance of apoptosis and proliferation plays a key role. Of this study is to summarize our current knowledge of the cell kinetical alterations considering histological activity of disease. On the basis of current understanding it is known that the apoptosis and proliferation of epithelial cells increase in active inflammation compare to normal, although an uniform standpoint of evaluating is still missing. Some alterations of apoptosis and antigen presentation are described in the mononuclear cells of the subepithelial layer. Getting acquainted with and describing the changes of cell ...
The imbalance of epithelial cell kinetics in ulcerative colitis can lead to several gastrointesti... more The imbalance of epithelial cell kinetics in ulcerative colitis can lead to several gastrointestinal disorders such as ulcers or neoplasias. The changes of epithelial cell kinetics caused by the inflammatory process have not been fully and uniformly described. Aim of the study was to compare the rate of epithelial cell apoptosis and proliferation within colonic crypts considering the histological activity of ulcerative colitis. Formalin fixed paraffin embedded biopsy specimens from mild, moderate, and severe active inflammation of ulcerative colitis and from normal colonic tissue were observed. Number of cases (apoptosis/proliferation): normal: 8/10; mild UC: 8/10; moderate: 8/8; severe: 12/8. For detecting apoptosis the TUNEL-POD-DAB method, and for proliferation the PCNA (PC-10)-Biotin-Streptavidin-AEC method were used, constrained with haematoxylin. Using light microscope, at least 500 crypt epithelial cells were encountered axially in whole, well-orientated colonic crypts per ea...
The molecular biological analysis of rare cell samples has become increasingly important in medic... more The molecular biological analysis of rare cell samples has become increasingly important in medical research and applications. Using laser microdissection and special macromolecule isolation techniques allows us to understand the biological information even in a single cell and to examine the genetical and proteomical features of biologically homogenous cell populations. There are several type of laser microdissectors which have a very user-friendly actuation. In practice the most difficult parts are the sample preparation and the macromolecule extraction from rare cell samples. The aims of this study are to summarize current practical experiences and to foreshow the application possibilities of this quite new technique in clinical practice.
The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative coli... more The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative colitis. The changes of such regenerative and immortalizing pathways caused by the inflammatory process that are proved to be carcinogenic in other human tissues have not been fully and uniformly described. Aim of the study was to describe the expression alterations of regenerative signal receptors and cell aging inhibitory systems within colonic crypts considering the histological activity of the disease. I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue. In mild inflammation all observed parameter showed significantly elevated protein expression ...
World journal of gastroenterology : WJG, Jan 7, 2007
To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9)... more To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett's metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with reflux esophagitis (n = 7), Barrett's metaplasia (n = 14), Barrett and esophagitis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant. GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett's metaplasia and the other groups. No major changes were observed between Barrett, es...
World journal of gastroenterology : WJG, Jan 21, 2015
Epithelial layer of the intestine relies upon stem cells for maintaining homeostasis and regenera... more Epithelial layer of the intestine relies upon stem cells for maintaining homeostasis and regeneration. Two types of stem cells are currently defined in intestinal crypts: the cycling crypt base columnar cells and quiescent cells. Though several candidate markers and regulators of rapidly cycling and quiescent stem cells have been identified so far, the exact nature of quiescent cells is still questionable since investigations mainly focused on candidate markers rather than the label-retaining population itself. Recent results, however, have strengthened the argument for functional plasticity. Using a lineage tracing strategy label-retaining cells (LRCs) of the intestinal epithelium were marked, then followed by a pulse-chase analysis it was found that during homeostasis, LRCs were Lgr5-positive and were destined to become Paneth and neuroendocrine cells. Nevertheless, it was demonstrated that LRCs are capable of clonogenic growth by recall to the self-renewing pool of stem cells in ...
Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and... more Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line. Colonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n3 = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n1 = 6; n2 = 6; n3 = 6) and independent samples ((n1 = 6; n2 = 6; n3 = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n1 = 14; n2 = 20; n3 = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n1 = 5; n2 = 5; n3 = 9) was defined us...
In the intestine a balance between proinflammatory and repair signals of the immune system is ess... more In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;largely antitumorigenic&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;largely pro-tumorigenic&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.
Background: The circulating tumor cells of solid tumors, especially in colorectal cancer has been... more Background: The circulating tumor cells of solid tumors, especially in colorectal cancer has been of great interest in medical research in the last and new century. Methods: A literature review of recent data for the preparation of a proposal for clinical applications. Results: Starting with the detection of circulating cancer cells in histological sections, lymph nodes, bone marrow and peripheral
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 2014
Early molecular detection of the colorectal dysplasia-carcinoma transition may augment the accura... more Early molecular detection of the colorectal dysplasia-carcinoma transition may augment the accuracy of diagnosis in case of biopsy orientation errors. The combination of high-throughput microarray-based biomarker screening with tissue microarray-based prospective protein biomarker expression analysis could represent an additional test in routine automated diagnostic procedures. Our aim was to test and select protein markers to identify protein expression profile alterations, focusing on the dysplasia-carcinoma transition in sporadic colorectal tumors. Dysplasia-carcinoma transition-specific transcript sets were previously identified using HGU133plus2 microarrays and Taqman RT-PCR cards. Here, 26 potential dysplasia-carcinoma transition-specific markers were tested by immunohistochemistry at the protein level using tissue microarrays in a total of 168 independent colonic biopsy samples. A set of 26 transcripts [including matrix metalloproteinase-3 (MMP3) and chemokine (C-X-C motif) l...
Background and aims: Though histopathology is still the gold standard for differentiating stages ... more Background and aims: Though histopathology is still the gold standard for differentiating stages of colorectal disease progression, the cut slide may represent only a fragment of the whole sample and disease features, such as dysplastic areas of flat adenomas, may remain hidden due to inappropriate sampling or tissue orientation. The early molecular detection of the colorectal dysplasia-carcinoma transition may enhance the strenght of diagnosis from colonic biopsies. Using high-throughput microarray-based biomarker screening low cost diagnostic array real-time PCR panels may be developed. We aimed to determine molecular markers for enhancing the differentiation of high-grade dysplasia from colorectal carcinoma (CRC) and to analyze the applicability of FFPE tissue samples. Material and Methods: Discriminatory transcript set was identified using HGU133plus2 microarrays (Affymetrix Inc.) on 53 biopsy samples (22 CRC, 20 adenoma, 11 normal). For testing the classificatory power of the discriminatory genes, 94 independent biopsies (27 CRC, 29 adenoma, 38 normal) were analyzed on microarrays. Array real-time PCR validation was done on 68 independent samples (24 CRC, 24 adenoma, 20 normal) using LightCycler®480 system (Roche) and RealTime ready assays. Reverse transcription was done using Transcriptor First Strand cDNA Synthesis Kit (Roche). For testing the applicability of FFPE tissues, total RNA was isolated from 10um-thick slides of 5 CRC and 2 adjacent normal samples using High Pure RNA Paraffin Kit (Roche). The same cDNA synthesis and real-time PCR conditions were applied as in case of fresh frozen samples. Results: A set of 11 transcripts was determined which could correctly discriminate between not only the normal, adenoma and CRC samples, but between high-grade dysplastic adenoma and CRC samples by 100% sensitivity and 88.9% specificity. The discriminatory power of the marker set was proved to be high on independent fresh frozen biopsy samples in both microarray and RT-PCR analyses. 95.6% of original and 94.1% of cross-validated samples were correctly classified in discriminant analysis. According to the RT-PCR results for the set of 11 markers, tumorous and normal FFPE tissue samples could be distinguished by 100% sensitivity and specificity. Conclusion: The identified transcripts could correctly characterize the dysplasia-carcinoma transition in colonic tissue samples, also on a large independent sample set and on FFPE tissue samples. These markers can establish the basis of gene expression based diagnostic classification of colorectal cancer. Diagnostic panels can become part of the automated routine procedure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1155. doi:1538-7445.AM2012-1155
World journal of gastroenterology : WJG, Jan 28, 2015
To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived gro... more To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor (HGFR)-expressing cells in active ulcerative colitis (UC). On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected. After preparing tissue microarrays and blood smears HGFR, caudal type homeobox 2 (CDX2), prominin-1 (CD133) and Musashi-1 conventional and double fluorescent immunolabelings were performed. Immunostained samples were digitalized using high-resolution Mirax Desk instrument, and analyzed with the Mirax TMA Module software. For semiquantitative counting of immunopositive lamina propria (LP) cells 5 fields of view were counted at magnification × 200 in each sample core, then mean ± SD were determined. In case of peripheral blood smears, 30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells ...
Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA... more Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples s...
World journal of gastroenterology : WJG, Jan 14, 2009
Peutz-Jeghers syndrome (PJS), a rare autosomal dominant inherited disorder, is characterized by h... more Peutz-Jeghers syndrome (PJS), a rare autosomal dominant inherited disorder, is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. Patients with this syndrome have a predisposition to a variety of cancers in multiple organs. Mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a major cause of PJS. Here we present the clinical and molecular findings of two unrelated Thai individuals with PJS. Mutation analysis by Polymerase Chain Reaction-sequencing of the entire coding region of STK11 revealed two potentially pathogenic mutations. One harbored a single nucleotide deletion (c.182delG) in exon 1 resulting in a frameshift leading to premature termination at codon 63 (p.Gly61AlafsX63). The other carried an in-frame 9-base-pair (bp) deletion in exon 7, c.907_915del9 (p.Ile303_Gln305del). Both deletions were de novo and have never been previously described. This study has expanded the genotypic spectrum of the STK11 gene.
The pathogenesis of inflammatory bowel diseases is still unknown, but is accessible from several ... more The pathogenesis of inflammatory bowel diseases is still unknown, but is accessible from several ways. One possibility is the immunohistochemical analysis of cellular changes in the intestinal mucosa. The increased epithelial cell turnover is connected with false immunological pathways in the subepithelial layer. Behind these disturbances which can lead to chronic remitting inflammatory processes the imbalance of apoptosis and proliferation plays a key role. Of this study is to summarize our current knowledge of the cell kinetical alterations considering histological activity of disease. On the basis of current understanding it is known that the apoptosis and proliferation of epithelial cells increase in active inflammation compare to normal, although an uniform standpoint of evaluating is still missing. Some alterations of apoptosis and antigen presentation are described in the mononuclear cells of the subepithelial layer. Getting acquainted with and describing the changes of cell ...
The imbalance of epithelial cell kinetics in ulcerative colitis can lead to several gastrointesti... more The imbalance of epithelial cell kinetics in ulcerative colitis can lead to several gastrointestinal disorders such as ulcers or neoplasias. The changes of epithelial cell kinetics caused by the inflammatory process have not been fully and uniformly described. Aim of the study was to compare the rate of epithelial cell apoptosis and proliferation within colonic crypts considering the histological activity of ulcerative colitis. Formalin fixed paraffin embedded biopsy specimens from mild, moderate, and severe active inflammation of ulcerative colitis and from normal colonic tissue were observed. Number of cases (apoptosis/proliferation): normal: 8/10; mild UC: 8/10; moderate: 8/8; severe: 12/8. For detecting apoptosis the TUNEL-POD-DAB method, and for proliferation the PCNA (PC-10)-Biotin-Streptavidin-AEC method were used, constrained with haematoxylin. Using light microscope, at least 500 crypt epithelial cells were encountered axially in whole, well-orientated colonic crypts per ea...
The molecular biological analysis of rare cell samples has become increasingly important in medic... more The molecular biological analysis of rare cell samples has become increasingly important in medical research and applications. Using laser microdissection and special macromolecule isolation techniques allows us to understand the biological information even in a single cell and to examine the genetical and proteomical features of biologically homogenous cell populations. There are several type of laser microdissectors which have a very user-friendly actuation. In practice the most difficult parts are the sample preparation and the macromolecule extraction from rare cell samples. The aims of this study are to summarize current practical experiences and to foreshow the application possibilities of this quite new technique in clinical practice.
The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative coli... more The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative colitis. The changes of such regenerative and immortalizing pathways caused by the inflammatory process that are proved to be carcinogenic in other human tissues have not been fully and uniformly described. Aim of the study was to describe the expression alterations of regenerative signal receptors and cell aging inhibitory systems within colonic crypts considering the histological activity of the disease. I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue. In mild inflammation all observed parameter showed significantly elevated protein expression ...
World journal of gastroenterology : WJG, Jan 7, 2007
To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9)... more To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett's metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with reflux esophagitis (n = 7), Barrett's metaplasia (n = 14), Barrett and esophagitis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant. GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett's metaplasia and the other groups. No major changes were observed between Barrett, es...
World journal of gastroenterology : WJG, Jan 21, 2015
Epithelial layer of the intestine relies upon stem cells for maintaining homeostasis and regenera... more Epithelial layer of the intestine relies upon stem cells for maintaining homeostasis and regeneration. Two types of stem cells are currently defined in intestinal crypts: the cycling crypt base columnar cells and quiescent cells. Though several candidate markers and regulators of rapidly cycling and quiescent stem cells have been identified so far, the exact nature of quiescent cells is still questionable since investigations mainly focused on candidate markers rather than the label-retaining population itself. Recent results, however, have strengthened the argument for functional plasticity. Using a lineage tracing strategy label-retaining cells (LRCs) of the intestinal epithelium were marked, then followed by a pulse-chase analysis it was found that during homeostasis, LRCs were Lgr5-positive and were destined to become Paneth and neuroendocrine cells. Nevertheless, it was demonstrated that LRCs are capable of clonogenic growth by recall to the self-renewing pool of stem cells in ...
Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and... more Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line. Colonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n3 = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n1 = 6; n2 = 6; n3 = 6) and independent samples ((n1 = 6; n2 = 6; n3 = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n1 = 14; n2 = 20; n3 = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n1 = 5; n2 = 5; n3 = 9) was defined us...
In the intestine a balance between proinflammatory and repair signals of the immune system is ess... more In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;largely antitumorigenic&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;largely pro-tumorigenic&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.
Background: The circulating tumor cells of solid tumors, especially in colorectal cancer has been... more Background: The circulating tumor cells of solid tumors, especially in colorectal cancer has been of great interest in medical research in the last and new century. Methods: A literature review of recent data for the preparation of a proposal for clinical applications. Results: Starting with the detection of circulating cancer cells in histological sections, lymph nodes, bone marrow and peripheral
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