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Find video protocols related to scientific articles indexed in Pubmed.
Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome.
BMC Cancer
PUBLISHED: 05-21-2014
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Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer.
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Differential expression of galectin-1 and galectin-3 in canine non-malignant and malignant mammary tissues and in progression to metastases in mammary tumors.
Anticancer Res.
PUBLISHED: 04-30-2014
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Galectin-1 and galectin-3 are carbohydrate-binding proteins that have been implicated in the pathobiology of several types of cancer. The aim of the present study was to investigate the expression pattern of both these galectins in canine non-neoplastic mammary tissues and mammary tumors (CMT).
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Differentiation reprogramming in gastric intestinal metaplasia and dysplasia: role of SOX2 and CDX2.
Histopathology
PUBLISHED: 04-14-2014
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Intestinal metaplasia (IM), which results from de-novo expression of CDX2, and dysplasia are precursor lesions of gastric cancer that are associated with an increased risk for cancer development. There is much evidence suggesting a role for the transcription factor SOX2 in gastric differentiation. The aim of this study was to attempt to establish the relationship of SOX2 with CDX2 and with the differentiation reprogramming that characterizes gastric carcinogenesis, to assess their involvement in IM and dysplasia.
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Sociodemographic determinants of prevalence and incidence of Helicobacter pylori infection in Portuguese adults.
Helicobacter
PUBLISHED: 06-03-2013
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Understanding the determinants of Helicobacter pylori infection in adults is essential to predict the burden of H. pylori-related diseases. We aimed to estimate the prevalence and incidence of H. pylori infection and to identify its major sociodemographic correlates in an urban population from the North of Portugal.
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CDX2 regulation by the RNA-binding protein MEX3A: impact on intestinal differentiation and stemness.
Nucleic Acids Res.
PUBLISHED: 02-13-2013
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The homeobox transcription factor CDX2 plays a crucial role in intestinal cell fate specification, both during normal development and in tumorigenic processes involving intestinal reprogramming. The CDX2 regulatory network is intricate, but it has not yet been fully uncovered. Through genome-wide screening of a 3D culture system, the RNA-binding protein MEX3A was identified as putatively involved in CDX2 regulation; therefore, its biological relevance was addressed by setting up cell-based assays together with expression studies in murine intestine. We demonstrate here that MEX3A has a repressive function by controlling CDX2 levels in gastric and colorectal cellular models. This is dependent on the interaction with a specific binding determinant present in CDX2 mRNA 3untranslated region. We have further determined that MEX3A impairs intestinal differentiation and cellular polarization, affects cell cycle progression and promotes increased expression of intestinal stem cell markers, namely LGR5, BMI1 and MSI1. Finally, we show that MEX3A is expressed in mouse intestine, supporting an in vivo context for interaction with CDX2 and modulation of stem cell properties. Therefore, we describe a novel CDX2 post-transcriptional regulatory mechanism, through the RNA-binding protein MEX3A, with a major impact in intestinal differentiation, polarity and stemness, likely contributing to intestinal homeostasis and carcinogenesis.
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Is cardia cancer aetiologically different from distal stomach cancer?
Eur. J. Cancer Prev.
PUBLISHED: 05-04-2011
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The coexistence of two aetiologically distinct types of cardia cancer, with distinctive histological characteristics of the neoplastic and nonneoplastic gastric mucosa, may explain the heterogeneous evidence of its association with Helicobacter pylori infection. We compared gastric cardia and noncardia cancers with regard to the frequency of H. pylori infection, the histological characteristics of the nonneoplastic gastric mucosa and the tumour histological type. We evaluated 41 cardia and 339 noncardia cancer cases undergoing gastrectomy, and 380 community controls. H. pylori infection and CagA infection status were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Histological characteristics of the neoplastic and nonneoplastic mucosa were obtained from pathology reports. The association between infection and cancers with different location was quantified in a case-control analysis and cardia and noncardia cancers were further compared. No positive relation was found for H. pylori infection, but CagA-positive strains were associated with an increased risk of noncardia cancer (odds ratio=1.60, 95% confidence interval=1.17-2.18). Twenty-seven (65.8%) cardia cancer cases, predominantly of the intestinal type (66.7%), had nonneoplastic atrophic mucosa and 208 (61.4%) noncardia cancers (56.7% of the intestinal type). Among the cases occurring in nonatrophic patients, the proportion of cancers of the Lauréns intestinal type was 71.4% for cardia and 54.2% for noncardia gastric cancers. Cardia and noncardia cancers were similar with regard to the relation with infection, histological type and condition of the nonneoplastic mucosa, supporting the predominance of cardia cancers determined by H. pylori infection in this European high-risk setting.
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CDX2 autoregulation in human intestinal metaplasia of the stomach: impact on the stability of the phenotype.
Gut
PUBLISHED: 12-09-2010
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Intestinal metaplasia (IM) is a gastric preneoplastic lesion that appears following Helicobacter pylori infection and confers an increased risk for development of cancer. It is induced by gastric expression of the intestine-specific transcription factor CDX2. The regulatory mechanisms involved in triggering and maintaining gastric CDX2 expression have not been fully elucidated. The Cdx2(+/-) mouse develops intestinal polyps with gastric differentiation and total loss of Cdx2 expression in the absence of structural loss of the second allele, suggesting a regulatory defect. This putative haplo-insufficiency, together with the apparent stability of IM, led to the hypothesis that CDX2 regulates its own expression through an autoregulatory loop in both contexts.
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DFNB1-associated deafness in Portuguese cochlear implant users: prevalence and impact on oral outcome.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 04-20-2010
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Hearing loss is a condition that interferes with the development of the child at a cognitive and language level. Therefore, early diagnosis of deafness is important for (re)habilitation, namely through the use of cochlear implant (CI). The present study aimed at screening CI Portuguese individuals for the presence of mutations in the genes GJB2 and GJB6 (DFNB1 locus), and searching a possible correlation between the genotype and the oral habilitation outcome following implantation.
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Relevance of high virulence Helicobacter pylori strains and futility of CDX2 expression for predicting intestinal metaplasia after eradication of infection.
Scand. J. Gastroenterol.
PUBLISHED: 04-07-2010
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Different Helicobacter pylori genotypes are associated with distinct inflammatory responses and consequent development of pre-neoplastic lesions, namely intestinal metaplasia (IM), which is dependent on the expression of CDX2. We aimed to evaluate IM progression/regression in the context of H. pylori eradication, bringing into play the effect of the virulence of infecting H. pylori strains and the hypothesis that CDX2 expression might be a marker for later development of IM.
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Factors contributing to the underestimation of Helicobacter pylori-associated gastric cancer risk in a high-prevalence population.
Cancer Causes Control
PUBLISHED: 03-23-2010
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This study aimed to identify sources of underestimation of the association between Helicobacter pylori infection and non-cardia gastric cancer, in a high-risk European population.
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Pathophysiology of intestinal metaplasia of the stomach: emphasis on CDX2 regulation.
Biochem. Soc. Trans.
PUBLISHED: 03-20-2010
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IM (intestinal metaplasia) of the stomach is a pre-neoplastic lesion that usually follows Helicobacter pylori infection and that confers increased risk for gastric cancer development. After setting the role played by CDX2 (Caudal-type homeobox 2) in the establishment of gastric IM, it became of foremost importance to unravel the regulatory mechanisms behind its de novo expression in the stomach. In the present paper, we review the basic pathology of gastric IM as well as the current knowledge on molecular pathways involved in CDX2 regulation in the gastric context.
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Juvenile polyps have gastric differentiation with MUC5AC expression and downregulation of CDX2 and SMAD4.
Histochem. Cell Biol.
PUBLISHED: 02-12-2009
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CDX2 is a homeobox transcription factor that works as a master gene in intestinal differentiation, both in the colon and in aberrant locations such as intestinal metaplasia (IM) of the stomach. Transgenic mice with Cdx2 expression in the stomach develop IM and Cdx2(+/-) mice develop hamartomatous polyps in the colon presenting gastric differentiation. We previously observed regulation of CDX2 by the BMP/SMAD pathway in the gastric context. Here, we hypothesized that juvenile polyps, which are hamartomatous polyps caused by mutations in members of the BMP/SMAD pathway, might recapitulate the gastric differentiation observed in Cdx2(+/-) mice due to SMAD4 and CDX2 downregulation. We characterized SMAD4 and CDX2 expression in a series of 18 solitary juvenile polyps and 2 polyps from juvenile polyposis (JP) patients, one with a germline SMAD4 mutation and one with a germline BMPRIA mutation, as well as the expression of an intestinal differentiation marker, MUC2 (by immunohistochemistry and in situ hybridization), and gastric differentiation markers, MUC5AC and MUC6 (by immunohistochemistry). We observed that juvenile polyps have a heterogeneous expression of CDX2, MUC2 and SMAD4, with negative areas, and 15 of the 18 solitary polyps and the JP case with SMAD4 mutation exhibit de novo expression of MUC5AC but not MUC6. In conclusion, juvenile polyps have gastric transdifferentiation associated with downregulation of CDX2 and SMAD4, lending support to the role of the BMP/SMAD pathway in CDX2 regulation.
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Microalgal compounds modulate carcinogenesis in the gastrointestinal tract.
Trends Biotechnol.
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Gastrointestinal cancers rank second in overall cancer-related deaths. Carotenoids, sulfated polysaccharides, and polyunsaturated fatty acids (PUFAs) from microalgae exhibit cancer chemopreventive features at different stages of carcinogenesis. For instance, sulfated polysaccharides bear a prophylactic potential via blocking adhesion of pathogens to the gastric surface, whereas carotenoids are effective against Helicobacter pylori infection. This effect is notable because H. pylori has been targeted as the primary cause of gastric cancer. Recent results on antitumor and antibacterial compounds synthesized by microalgae are reviewed here, with an emphasis on their impact upon H. pylori infection and derived pathologies accompanying the progression of gastric carcinogenesis.
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Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors.
Dev. Cell
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How dermal papilla (DP) niche cells regulate hair follicle progenitors to control hair growth remains unclear. Using Tbx18(Cre) to target embryonic DP precursors, we ablate the transcription factor Sox2 early and efficiently, resulting in diminished hair shaft outgrowth. We find that DP niche expression of Sox2 controls the migration speed of differentiating hair shaft progenitors. Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased BMP inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we identify upregulated BMP signaling in knockout hair shaft progenitors and demonstrate that Bmp6 inhibits cell migration, an effect that can be attenuated by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and shows reduced migration and increased BMP activity of hair shaft progenitors. Collectively, our data identify Sox2 as a key regulator of hair growth that controls progenitor migration by fine-tuning BMP-mediated mesenchymal-epithelial crosstalk.
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Gastric intestinal metaplasia revisited: function and regulation of CDX2.
Trends Mol Med
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Intestinal metaplasia of the stomach is a preneoplastic lesion that appears following Helicobacter pylori infection and confers increased risk for gastric cancer development. However, the molecular networks connecting infection to lesion formation and the cellular origin of this lesion remain largely unknown. A more comprehensive understanding of how intestinal metaplasia arises and is maintained will be a major breakthrough towards developing novel therapeutic interventions. Furthermore, after ascertaining the pivotal role of CDX2 in establishing and maintaining intestinal metaplasia, it becomes important to decipher the upstream molecular pathways leading to its ectopic expression. Here, we review the pathophysiology of intestinal metaplasia in the context of the molecular network involved in its establishment and maintenance, with emphasis on CDX2 function and regulation.
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Helicobacter pylori and the BMP pathway regulate CDX2 and SOX2 expression in gastric cells.
Carcinogenesis
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Helicobacter pylori infection is the main risk factor for intestinal metaplasia (IM) and gastric cancer development. IM is a pre-neoplastic lesion, induced by the transcription factor CDX2, where the gastric mucosa is converted to an intestinal phenotype. We previously demonstrated that key elements of the bone morphogenetic protein (BMP) pathway co-localize with CDX2 in IM and upregulate CDX2 expression in gastric cell lines. These observations, together with the hypothesis that CDX2 could be repressed by SOX2, led us to test whether H. pylori, through BMPs, SOX2 and CDX2 could participate in a molecular network critical for the development of IM. AGS cells with and without SMAD4 knock-down were co-cultured with H. pylori or BMP2 to assess the expression of BMP pathway members as well as CDX2 and SOX2 by qPCR and western blot. Proximity ligation assay (PLA) was also performed to evaluate SMAD proteins interaction. Immunohistochemistry and western blot were performed in gastric samples from mice infected with Helicobacter spp. to measure Smad4, pSmad1/5/8, Cdx2 and Sox2 expression in vivo. Increased expression and activity of the BMP pathway accompanied by CDX2 upregulation and SOX2 downregulation were observed in AGS cells co-cultured with H. pylori or BMP2. These effects were impaired by downregulation of the BMP pathway. Finally, infected mice present BMP pathway upregulation, focal Cdx2 expression and decreased Sox2. These results provide a novel link between H. pylori infection and the BMP pathway in the regulation of intestinal and gastric-specific genes that might be relevant for gastric IM.
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Determinants of gastric CDX2 expression: a study in Mozambique.
Eur. J. Cancer Prev.
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As CDX2 expression precedes the occurrence of gastric preneoplastic lesions in the intestinal differentiation pathway, study of these steps of gastric carcinogenesis may contribute toward understanding the early effects of gastric cancer determinants. Our aim was to quantify the association between Helicobacter pylori infection and other environmental factors and the gastric expression of CDX2. Dyspeptic patients undergoing an upper digestive endoscopy (Gastroenterology Department, Maputo Central Hospital) were consecutively invited to participate in this study and classified as having normal stomach/chronic nonatrophic gastritis (NS/CNAG), chronic atrophic gastritis (CAG), or intestinal metaplasia (IM). For all patients with CAG or IM and a subsample of NS/CNAG patients (sex-matched and age-matched, 1 : 2), H. pylori infection and CDX2 gene expression were assessed by histology and PCR and by immunohistochemistry, respectively. Age-adjusted, sex-adjusted, education-adjusted, and H. pylori infection-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were computed. CDX2 expression was observed in 56 NS/CNAG (49.1%), 39 CAG (86.7%), and all IM patients (n=12). It was more frequent among the H. pylori-infected patients (OR=2.26, 95% CI: 1.00-5.15). Infection with high-virulence strains was associated with CDX2 expression in patients with CAG (cagA, OR=3.20, 95% CI: 1.35-7.52) and IM (vacA m1, OR=5.86, 95% CI: 1.08-31.62). Patients with a lower frequency of vegetable consumption had a higher risk of marked CDX2 expression (OR=3.64, 95% CI: 1.02-12.95). The virulence of the infecting strains and vegetable consumption were associated with CDX2 expression and may play a role in the progression to more advanced lesions.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.