Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Neurogastroenterol Motil ; 23(11): 1020-8, e497, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21883699

RESUMO

BACKGROUND: The transient receptor potential vanilloid 4 (TRPV4), a thermo-sensitive stretch-activated cation channel, is expressed in the skin stratified squamous epithelium, contributing to the acquisition of barrier function. Similarly, functional TRPV4 may be located in the stratified squamous epithelial lining of the esophagus, being involved in the pathogenesis of gastroesophageal reflux disease (GERD). Here we investigated the expression of TRPV4 in the mouse esophageal epithelium. METHODS: TRPV4 expression at the mRNA and protein levels was examined by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. A calcium imaging technique and ATP assay were used to evaluate the functionality of TRPV4 in freshly isolated esophageal epithelial cells. KEY RESULTS: Transcripts and proteins encoding TRPV4 were colocalized in the basal and intermediate layers of the esophageal epithelium. Both 4α-phorbol 12,13- didecanoate (4α-PDD), a selective agonist for TRPV4, and hypo-osmolar solution (160 mOsm) elevated the intracellular calcium concentration ([Ca(2+) ](i) ) in a subset of the isolated cells (70%). These [Ca(2+) ](i) increases were potently inhibited by ruthenium red (RuR), a TRPV4 channel antagonist, and were suppressed by extracellular protons (pH 5.0). Finally, application of 4α-PDD evoked ATP release in primary esophageal epithelial cells. CONCLUSIONS & INFERENCES: Acid-sensitive TRPV4 channels were mainly expressed in the esophageal epithelial cells of the basal and intermediate layers. Direct exposure of TRPV4-expressing cells to gastric acid, as would occur in cases of GERD, could influence their cellular functions, possibly aggravating the disease state.


Assuntos
Ácidos/metabolismo , Cálcio/metabolismo , Células Epiteliais/fisiologia , Esôfago/citologia , Canais de Cátion TRPV/metabolismo , Animais , Células Epiteliais/citologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Canais de Cátion TRPV/genética
2.
Methods Find Exp Clin Pharmacol ; 32(4): 243-6, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20508872

RESUMO

Primary Helicobacter pylori eradication rate using triple therapy (a proton pump inhibitor [PPI] + amoxicillin [AMPC] + clarithromycin [CAM], over 7 days) is showing a declining trend. In this study we report recent eradication rates and have evaluated the usefulness of a pack preparation of three drugs. H. pylori eradication rate was 85.1% (57/67) in 2004 but then fell to 75.2% (79/105) in 2005, 70.1% (68/97) in 2006 and 69.9% (58/83) in 2007. With the introduction of packs (lansoprazole [LPZ] 60 mg, AMPC 1500 mg, CAM 400 mg) the eradication rate recovered to 78.0% (110/141) in 2008. A comparative study in 2008 delineated that the eradication rate in the pack group (88.4%, 38/43) was significantly higher than that of the conventional group (73.5%, 72/98). These results suggest that packs of eradication medicine are useful in increasing eradication success.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Adulto , Idoso , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Claritromicina/administração & dosagem , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos
3.
Br J Cancer ; 100(8): 1320-9, 2009 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-19337254

RESUMO

BCL6 is a transcriptional repressor that has important functions in lymphocyte differentiation and lymphomagenesis, but there have been no reports of BCL6 expression in gastric cancers. In the present study, we investigated the BCL6 function in gastric cancers. Treatment with TPA resulted in BCL6 degradation and cyclin D2 upregulation. This phenomenon was inhibited by the suppression of the nuclear translocation of HB-EGF-CTF (C-terminal fragment of pro-HB-EGF). The HB-EGF-CTF nuclear translocation leads to the interaction of BCL6 with HB-EGF-CTF and the nuclear export of BCL6, and after that BCL6 degradation was mediated by ubiquitin/proteasome pathway. Real-time RT-PCR and siRNA targeting BCL6 revealed that BCL6 suppresses cyclin D2 expression. Our data indicate that BCL6 interacts with nuclear-translocated HB-EGF-CTF and that the nuclear export and degradation of BCL6 induces cyclin D2 upregulation. We performed immunohistochemical analyses of BCL6, HB-EGF and cyclin D2 in human gastric cancers. The inverse correlation between BCL6 and cyclin D2 was also found in HB-EGF-positive human gastric cancers. BCL6 degradation caused by the HB-EGF-CTF also might induce cyclin D2 expression in human gastric cancers. Inhibition of HB-EGF-CTF nuclear translocation and maintenance of BCL6 function are important for the regulation of gastric cancer progression.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/genética , Idoso , Linhagem Celular Tumoral , Ciclina D2 , Ciclinas/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Fosforilação , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , RNA Neoplásico/genética , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/patologia , Supressão Genética
4.
Histol Histopathol ; 24(1): 31-40, 2009 01.
Artigo em Inglês | MEDLINE | ID: mdl-19012242

RESUMO

RUNX3 is a novel tumor suppressor in gastric carcinogenesis and an important factor for differentiation of chief cells in the normal gastric fundic mucosa. In this study, we confirmed RUNX3 immunolocalization in the fundic gland (bottom part) but minimum in surface mucous cell epithelium (top part) in the isolated gland from fundic mucosa. We also analyzed RUNX3 expression by immunohistochemistry in 102 gastric cancers and made a histological assessment of the expression of differentiation markers to evaluate interrelations. Among them, 45 and 57 cases were judged to be RUNX3 positive and negative, respectively, and 33 and 69 cases were pepsinogen I positive and negative, with no link to histological types. RUNX3 expression was significantly associated with that of pepsinogen I (P<0.001), but not mucins, including MUC5AC and MUC6, or the parietal or intestinal phenotypes. In conclusion, the present study showed, for the first time to our knowledge, a relation between RUNX3 and pepsinogen I expression in human gastric cancers. RUNX3 is strongly associated with chief cell phenotypic expression in human gastric cancers, as well as in normal gastric mucosa, and could be considered to play an important role in maintaining the chief cell phenotype.


Assuntos
Adenocarcinoma/metabolismo , Celulas Principais Gástricas/citologia , Celulas Principais Gástricas/metabolismo , Subunidade alfa 3 de Fator de Ligação ao Core/biossíntese , Neoplasias Gástricas/metabolismo , Idoso , Diferenciação Celular , Feminino , Imunofluorescência , Mucosa Gástrica/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucina-5AC/biossíntese , Mucina-6/biossíntese , Pepsinogênio A/biossíntese , RNA Mensageiro/análise
5.
Histol Histopathol ; 23(5): 593-9, 2008 05.
Artigo em Inglês | MEDLINE | ID: mdl-18283644

RESUMO

AIMS: The intake of salt and salty food is known as a risk factor for gastric cancer. We have previously demonstrated that a high-salt diet dose-dependently enhances Helicobacter pylori (H. pylori)-associated gastritis and stomach carcinogenesis in Mongolian gerbils. In this study, we focused on the influence of excessive salt intake on the expression of inflammatory mediators involved in progression of H. pylori-induced chronic gastritis. METHODS AND RESULTS: A total of 45 stomach samples from Mongolian gerbils were evaluated by immunohistochemistry. The animals were infected with H. pylori and fed basal (0.32%) or a high-salt (10%) diet, and sacrificed after 40 weeks. Proliferative activity and expression of cyclooxygenase-2 (COX-2) in gastric mucosa were significantly increased in H. pylori-infected gerbils. The additional high-salt diet significantly up-regulated the expression of inducible nitric oxide synthase (iNOS) and COX-2 in H. pylori-infected groups (P<0.01 and P<0.05, respectively), while no significant effects were noted in non-infected animals. There was significant synergistic interaction between H. pylori infection and 10% NaCl diet on the expression of iNOS (P<0.05) and also a tendency for enhanced COX-2 expression (P=0.0599). CONCLUSIONS: The present results suggest that a high-salt diet works synergistically with H. pylori infection to enhance iNOS and COX-2 expression in the gastric mucosa of Mongolian gerbils, and support the hypothesis that excessive salt intake may be associated with progression of H. pylori-induced gastritis.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Óxido Nítrico Sintase Tipo II/metabolismo , Cloreto de Sódio/administração & dosagem , Ração Animal , Animais , Bromodesoxiuridina/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Técnica Indireta de Fluorescência para Anticorpo , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Gerbillinae , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/patologia , Técnicas Imunoenzimáticas , Regulação para Cima
6.
Histol Histopathol ; 22(6): 641-9, 2007 06.
Artigo em Inglês | MEDLINE | ID: mdl-17357094

RESUMO

AIMS: We have previously demonstrated the importance of gastric and intestinal phenotypic expression for stomach carcinogenesis. In this study, we focused on Epstein-Barr virus (EBV)-associated stomach cancers, with special attention to Cdx2. METHODS AND RESULTS: We evaluated the expression of gastric and intestinal phenotypic markers by immunohistochemistry in 35 EBV-positive [EBV (+)] and 75 EBV-negative [EBV (-)] stomach cancers in Colombia. The lesions were divided phenotypically into gastric (G), gastric-and-intestinal mixed (GI), intestinal (I), and null (N) phenotypes. In the EBV (+) cases, the lesions were divided phenotypically into 9 G (25.7%), 1 GI (2.9%), 3 I (8.6%), and 22 N (62.9%) types. Similarly, the EBV (-) lesions were also classified phenotypically as 15 G (20.0%), 19 GI (25.3%), 24 I (32.0%), and 17 N (22.7%) types. The proportion of N type EBV (+) lesions was higher than for their EBV (-) counterparts (P<0.0001). The expression of Cdx2 and MUC2 was also found to be significantly lower in EBV (+) than in EBV (-) stomach cancers (P=0.0001; P<0.0001). Cdx2 expression in the intestinal metaplastic glands present in non-neoplastic mucosa surrounding EBV (+) lesions was also significantly lower than in EBV (-) tumors (P=0.016) despite no evidence of EBV infection. CONCLUSIONS: EBV (+) stomach cancers are characterized by low expression of intestinal phenotype markers, including Cdx2, and only occasional gastric phenotypic expression.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/virologia , Biomarcadores Tumorais/análise , Infecções por Vírus Epstein-Barr/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/virologia , Adenocarcinoma/patologia , Fator de Transcrição CDX2 , Regulação para Baixo , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4 , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Mucina-2 , Mucinas/metabolismo , Fenótipo , RNA Viral/metabolismo , Neoplasias Gástricas/patologia
7.
Oncogene ; 26(24): 3511-20, 2007 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-17160019

RESUMO

Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate beta-catenin/T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Here, we show that Wnt signaling can cause chromosomal instability (CIN). As an indicator of CIN, we scored anaphase bridge index (ABI) in mouse polyps and ES cells where Wnt signaling was activated by Apc or beta-catenin mutations. We found three to nine times higher ABI than in wild-type controls. Furthermore, karyotype analysis confirmed that the Wnt signal-activated ES cells produced new chromosomal aberrations at higher rates; hence CIN. Consistently, expression of dominant-negative TCFs in these cells reduced their ABI. We also found that Wnt signal activation increased phosphorylation of Cdc2 (Cdk1) that inhibited its activity, and suppressed apoptosis upon exposure of the cells to nocodazole or colcemid. The data suggest that Wnt signaling stimulates the cells to escape from mitotic arrest and apoptosis, resulting in CIN. In human gastric cancer tissues with nuclear beta-catenin, ABI was significantly higher than in those without. These results collectively indicate that beta-catenin/TCF-mediated transcription itself increases CIN through dysregulation of G2/M progression.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Instabilidade Cromossômica , Mutação , Fatores de Transcrição TCF/genética , beta Catenina/genética , Adenoma/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Animais , Divisão Celular/genética , Sobrevivência Celular/genética , Células Cultivadas , Aberrações Cromossômicas , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Células-Tronco Embrionárias , Fase G2/genética , Humanos , Neoplasias Intestinais/genética , Pólipos Intestinais/genética , Camundongos , Microtúbulos/metabolismo , Transdução de Sinais , Fatores de Transcrição TCF/metabolismo , Transcrição Gênica , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
8.
Histol Histopathol ; 22(3): 251-60, 2007 03.
Artigo em Inglês | MEDLINE | ID: mdl-17163399

RESUMO

AIMS: We have previously demonstrated links between clinicopathological findings and phenotypes using several gastric and intestinal phenotypic markers in stomach and pancreatic cancers. However, the clinicopathological significance of the phenotype and Cdx2 expression has hitherto remained unclear in colorectal carcinogenesis. METHODS AND RESULTS: We examined the correlation between gastric and intestinal phenotypic expression in 91 primary early carcinomas of the colon. MUC2 expression demonstrated a significant decrease from tubular/tubulovillous adenomas with moderate atypia, through intramucosal carcinomas, to cancers with submucosal invasion (P<0.0001). Intramucosal de novo carcinomas (flat type carcinomas without adenomatous components) exhibited a greater decrease of MUC2 than intramucosal lesions with adenomatous components. Expression of MUC5AC also decreased significantly with progression according to the tubular/tubulovillous adenoma-carcinoma sequence, carcinomas with villous adenomatous components having a higher level compared with their tubular adenomatous counterparts, suggesting differences in the pathway of malignant transformation. Cdx2 nuclear expression was maintained in all of the adenomas and early carcinomas examined. CONCLUSIONS: Our data suggest that the reduction of MUC2 expression may be associated with the occurrence and progression of colorectal carcinomas in both adenoma-carcinoma sequence pathway and de novo carcinogenesis. Tumor-suppressive effects of Cdx2 may be preserved during early stages of colorectal carcinogenesis.


Assuntos
Adenocarcinoma/metabolismo , Adenoma Viloso/metabolismo , Neoplasias Colorretais/metabolismo , Mucinas/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenoma Viloso/patologia , Adenoma Viloso/cirurgia , Biomarcadores Tumorais/metabolismo , Fator de Transcrição CDX2 , Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Progressão da Doença , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Técnicas Imunoenzimáticas , Masculino , Proteínas dos Microfilamentos/metabolismo , Mucina-5AC , Mucina-2 , Mucina-6
9.
Histol Histopathol ; 22(3): 273-84, 2007 03.
Artigo em Inglês | MEDLINE | ID: mdl-17163401

RESUMO

We have previously suggested that an origin of a stomach cancer is from a progenitor cell specializing toward exocrine cell (Exo-cell) lineages. To clarify whether our hypothesis is correct or not, we analyzed the expression of Exo-cell and endocrine cell (End-cell) markers in a series of lesions for comparison. We evaluated chromogranin A (CgA) expression in 37 early and 73 advanced stomach cancers, in 30 stomach adenomas, in 8 carcinoid tumors, and in 4 endocrine cell carcinomas (ECCs) with assessment of gastric and/or intestinal (G/I) phenotypes in both Exo-cell and End-cell by immunohistochemistry. CgA expression was observed in 10.8% of the early and 16.4% of the advanced stomach cancers, respectively. The End-cell G/I phenotypes were in line with the Exo-cell counterparts in the CgA-positive stomach cancerous areas, and there was strong association between Cdx2 expression and the intestinal End-cell markers. All of the adenoma cases had the intestinal Exo-cell phenotypic expression, with the positive link between Exo-cell and End-cell G/I phenotypes. All stomach carcinoids had CgA expression but no expression of Exo-cell markers. In conclusion, most stomach cancers might develop from a progenitor cell specializing towards Exo-cell lineages, but some cases possessed both Exo-cell and End-cell markers with maturely differentiated phenotypes. In such cases, Exo-cell and End-cell phenotypes were found to correlate strongly, suggesting the possibility of histogenesis from "cancer stem cells".


Assuntos
Adenocarcinoma/secundário , Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Tumor Carcinoide/patologia , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Tumor Carcinoide/metabolismo , Contagem de Células , Cromogranina A/metabolismo , Glândulas Endócrinas/metabolismo , Glândulas Endócrinas/patologia , Glândulas Exócrinas/metabolismo , Glândulas Exócrinas/patologia , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/metabolismo
10.
Histopathology ; 49(6): 612-21, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17163846

RESUMO

AIMS: Abnormal localization of beta-catenin is frequently observed in human gastric cancers. The aim of the present study was to evaluate relationships among gastrointestinal differentiation phenotypes, beta-catenin localization and mutations of Wnt signalling genes. METHODS AND RESULTS: Seventy-seven regions in 39 gastric adenocarcinomas were classified according to beta-catenin localization and gastric and intestinal phenotypes. Cases with membranous beta-catenin localization showed a gradual decrease from gastric (G) (55% = 6/11) and gastric-and-intestinal-mixed (GI) (17% = 5/29) to intestinal (I) (0% = 0/21) phenotypes, while those with nuclear localization showed a concomitant increase: 18% (2/11), 41% (12/29), 95% (20/21) and 63% (10/16) for G, GI, I and null type (N), respectively (P < 0.001, membranous versus nuclear localization in G, GI through I). Mutations in exon 3 of the beta-catenin gene were found in G (50% = 1/2), GI (67% = 8/12), I (45% = 9/20) and N (0% = 0/10) regions with nuclear beta-catenin localization (GI versus N, P < 0.01; I versus N, P < 0.05). Adenomatous polyposis coli (APC) gene mutations were demonstrated only in GI, I and N types, irrespective of beta-catenin localization. Molecular analysis of these genes revealed 10 tumours to be heterogeneous out of 16 informative cases (62.5%). CONCLUSION: Intestinal phenotypic expression is accompanied by a shift from membranous to cytoplasmic/nuclear accumulation of beta-catenin. In contrast, N-type regions may progress along a different pathway.


Assuntos
Adenocarcinoma/genética , Núcleo Celular/metabolismo , Mucosa Intestinal/metabolismo , Mutação , Neoplasias Gástricas/genética , beta Catenina/genética , beta Catenina/metabolismo , Adenocarcinoma/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Núcleo Celular/patologia , Citoplasma/genética , Citoplasma/metabolismo , Citoplasma/patologia , Análise Mutacional de DNA , DNA de Neoplasias/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias Gástricas/patologia
12.
Histopathology ; 46(6): 649-58, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15910596

RESUMO

AIMS: Other than ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, the molecular mechanisms underlying gastric and intestinal phenotypes of human stomach adenocarcinomas have yet to be clarified in detail. We have reported that Sox2, an HMG-box gastric transcription factor, is expressed in normal gastric mucosa and down-regulated in intestinal metaplasia. METHODS AND RESULTS: We analysed mRNA levels of Sox2 and other differentiation markers in 50 surgically resected stomach adenocarcinomas, immunohistochemically classified into gastric (G), gastric-and-intestinal (GI)-mixed, solely intestinal (I), and null (N) types. Sox2 was found to be transcribed in G and GI-mixed type adenocarcinomas in accordance with MUC5AC and MUC6 expression, while Cdx1 and Cdx2 were up-regulated in GI-mixed and I types along with the expression of MUC2 and villin. In the N type, both gastric and intestinal transcription factors were suppressed. Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2. A stomach adenocarcinoma cell line, KATOIII, demonstrated both MUC5AC and Sox2, although MUC5AC mRNA was not detected in the Sox2+ AGS cell line. CONCLUSIONS: Sox2 may play an important role in maintaining a gastric phenotype in stomach cancers as well as in normal tissue, in cooperation with other cofactor(s).


Assuntos
Adenocarcinoma/patologia , Proteínas HMGB/genética , Neoplasias Intestinais/patologia , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Fator de Transcrição CDX2 , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas HMGB/análise , Proteínas de Homeodomínio/análise , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/metabolismo , Proteínas dos Microfilamentos/análise , Proteínas dos Microfilamentos/genética , Mucina-5AC , Mucina-6 , Mucinas/análise , Mucinas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOXB1 , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/análise
13.
Gastric Cancer ; 4(4): 185-91, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11846061

RESUMO

BACKGROUND: The caudal-type homeobox genes, Cdx1 and Cdx2, are candidates for directing intestinal development, differentiation, and maintenance of the intestinal phenotype. The aims of this study were: (1) to assess the normal tissue expression patterns of Cdx1 and Cdx2 in the human gastrointestinal tract and (2) to ascertain levels in intestinal metaplasia (IM) of the stomach associated with gastritis. METHODS: Fresh human tissues were collected by surgical resection from 39 patients after informed consent had been received. RNAs were extracted from 11 distinct sites in the gastrointestinal mucosa (gastric body, gastric antrum, duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), and Northern hybridization was performed for Cdr1 and Cdx2 mRNAs. In addition, RNAs were also extracted from normal gastric mucosa, and gastric mucosa with mild to severe IM, confirmed histopathologically. Reverse-transcriptase polymerase chain reaction (RT-PCR) was then carried out for Cdx1 and Cdx2. RESULTS: The expression of Cdx1 mRNA increased gradually from the duodenum to the distal colon, with no expression detected in the stomach. Compared with the distribution of Cdx1 mRNA in the mouse gastrointestinal tract, the expression of Cdr1 mRNA in the human gastrointestinal tract showed greater predominance in the jejunum and ileum. The expression of Cdx2 mRNA increased gradually from the duodenum to the proximal colon and decreased from the ascending colon to the rectum. Compared with the expression pattern of Cdx2 mRNA in the mouse gastrointestinal tract, the expression of Cdx2 mRNA in the human gastrointestinal tract showed greater predominance in the ileum. By RT-PCR, both Cdx1 and Cdx2 mRNAs were detected in the mild and severe types of IM. However, neither of these mRNAs was identified in normal gastric mucosa without IM. CONCLUSIONS: Cdr1 and Cdx2 mRNAs are widely present in the human intestinal and colonic mucosae, but not in the gastric mucosa, suggesting that their expression may contribute to the intestinal phenotype. The high levels of these mRNAs in IM mucosa associated with chronic atrophic gastritis point to an association with this phenotypic shift in the gastric mucosa.


Assuntos
Neoplasias Gastrointestinais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Mucosa Intestinal/patologia , RNA Mensageiro/biossíntese , Estômago/patologia , Adulto , Idoso , Northern Blotting , Fator de Transcrição CDX2 , Diferenciação Celular , Primers do DNA/química , Feminino , Mucosa Gástrica/metabolismo , Gastrite Atrófica/genética , Neoplasias Gastrointestinais/patologia , Proteínas de Homeodomínio/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Metaplasia , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...