HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression

Purpose To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma. Methods Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay. Result HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50% and the number of cells that migrated through the transwell insert was greatly decreased. The cell invasion rate was also significantly reduced. Moreover, typical markers of epithelial–mesenchymal transition such as E-cadherin, were increased, while vimentin and α–SMA were decreased after HIF-1α knockdown. In contrast, overexpression of DEC1 reversed the effects of HIF-1α knockdown. Cell proliferation, migration, and invasion were partially recovered. The level of E-cadherin was decreased, while the level of vimentin and α–SMA was increased. In addition, the level of β-catenin and LEF1 was downregulated after HIF-1α knockdown. The expression of MMP2 and MMP9 also declined. However, overexpression of DEC1 after HIF-1α knockdown partially reversed the expression pattern of these molecules. Conclusion HIF-1α contributed to EMT and metastasis through activation of canonical β-catenin signalling in choriocarcinoma and this process was dependent on DEC1. This study provides a new mechanism of HIF-1α in choriocarcinoma and suggests that intervention with DEC1 might be a promising therapeutic choice for choriocarcinoma (AU)

Resveratrol inhibits TGF-B1-induced EMT in gastric cancer cells through Hippo-YAP signaling pathway

To investigate the effects of resveratrol (RSVL) on epithelial-mesenchymal transition (EMT) and biological behaviors of gastric cancer cells.MethodsSGC-7901 cells were treated with RSVL, followed by TGF-β1 treatment for induction of EMT. Cell proliferation was tested by MTT assay, migration and invasion by Transwell and scratch assays, and Hippo-YAP signaling pathway activation by immunofluorescence. The RNA and protein expressions of E-cadherin, Vimentin, N-cadherin, and Snail were detected by qPCR and Western blot. A tumor model was constructed to examine the effect of RSVL on gastric tumor growth.ResultsRSVL inhibited the migration, invasion, and growth of gastric cancer cells in concentration- and time-dependent manners. RSVL inhibited TGF-β1-induced EMT of gastric cancer cells, which might relate to inactivation of the Hippo-YAP pathway. In the mouse tumor model, RSVL inhibited the EMT process by suppressing the Hippo-YAP pathway.ConclusionRSVL inhibited EMT of gastric cancer cells probably by weakening the Hippo-YAP signaling pathway. (AU)

Barrier proteins and eosinophilic esophagitis in children: the role of E-cadherin and filaggrin

This study aimed to assess the protein expression of E-cadherin and filaggrin (FLG) in the oesophagus of paediatric and adolescent patients diagnosed with eosinophilic esophagi-tis (EoE). It is a cross-sectional study conducted with 24 patients with EoE and 17 control patients, from June 2015 to June 2018. The histological analyses were performed by a trained pathologist. The protein expression of E-cadherin and FLG in oesophageal biopsy fragments was determined using an immunohistochemical technique. The epidemiological data were retrieved from medical records. There were no statistical differences in age and sex between case-patients and control patients. Food allergy was significantly higher in patients with EoE, as was the number of eosinophils present in the oesophageal biopsy materials. The immu-nohistochemical studies did not indicate FLG expression in any patient from the two groups. E-cadherin showed significantly reduced expression in patients with EoE. We concluded that FLG did not seem to play an important role in the mucosal alteration in EoE and that E-cadherin under expression could be a promising marker of epithelial damage in these patients.© 2022 Codon Publications. Published by Codon Publications (AU)

Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Background: To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patientswith oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredictable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax,E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition.Material and Methods: A cross-sectional study using genomic DNA and biopsy samples extracted from the oralmucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, UniversidadNacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test wasapplied to analyze immunostaining between controls/cases (p <0.05 was set for statistical significance).Results: GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation toCC “healthy” genotype (p=0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis(p=0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherinmarkers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, andBax immunomarker was diminished in OSCC.Conclusions: We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, whichmodifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G ofGJA1rs12197797 could be at risk of developing OSCC. (AU)

Knockdown of long non-coding RNA RP11-297P16.3 inhibits the migration and invasion of laryngeal squamous carcinoma cells

Purpose Laryngeal cancer has a poor prognosis when progressing to an advanced stage with limited treatment options. Therefore, understanding the underlying mechanisms is important to identify novel treatment targets. Long non-coding RNAs (lncRNAs) have been shown to play oncogenic roles in cancer, including in laryngeal cancer. We previously discovered that the lncRNA RP11-297P16.3 is overexpressed in laryngeal squamous cell carcinoma (LSCC) based on RNA-sequencing data. Therefore, the aim of the present study was to investigate the effects of knockdown of RP11-297P16.3 on the migration and invasion of LSCC cells, and the significance of these effects. Methods Six methods were employed to assess the function of RP11-297P16.3 including gene silencing, RT-PCR, the 5-Ethynyl-20-deoxyuridine (EdU) staining assay, Scratch wound-healing assay, transwell assay, and Western blot. Results The results show that the expression of RP11-297P16.3 in the si-lncRNA group was significantly decreased compared with those in the BC (blank control) and NC (negative control) groups. Moreover, knockdown of RP11-297P16.3 significantly inhibited the migration and invasion of LSCC cells but had no effect on cell proliferation. The protein expression of N-cadherin and vimentin was notably decreased after RP11-297P16.3 knockdown; whereas, the protein expression of cadherin was significantly increased Conclusion These results suggested that RP11-297P16.3 may inhibit the migration and invasion of LSCC cells by regulating the epithelial–mesenchymal transition process, suggesting that RP11-297P16.3 is a potential new target for treating LSCC (AU)

COL4A1, negatively regulated by XPD and miR-29a-3p, promotes cell proliferation, migration, invasion and epithelial–mesenchymal transition in liver cancer cells

Objective Collagen type IV alpha 1 (COL4A1) exerts tumor-promoting functions in several tumors. However, its role in liver cancer remains not fully understood. Hence, this study aims to investigate the role of COL4A1 in regulating liver cancer cell behaviors and to validate its upstream regulatory mechanism. Methods Expression of xeroderma pigmentosum D (XPD) and COL4A1 was examined by qRT-PCR and western blot. Cell proliferation, migration, and invasion were evaluated. The protein levels of N-cadherin, vimentin, and E-cadherin were determined by western blot to evaluate epithelial–mesenchymal transition (EMT). The interaction between miR-29a-3p and COL4A1 was analyzed by luciferase reporter assay. Results COL4A1 overexpression significantly promoted cell proliferation, migration, invasion, and EMT in Hep3B cells. In contrast, COL4A1 silencing yielded the opposite effects in HepG2 cells. Expression of COL4A1 was increased, whereas expression of XPD and miR-29a-3p was decreased in HCC tissues compared to controls. COL4A1 mRNA level was negatively correlated with expression of XPD and miR-29a-3p in HCC tissues. Furthermore, XPD silencing-mediated up-regulation of COL4A1 expression was attenuated by miR-29a-3p mimic. Moreover, miR-29a-3p mimic inhibited Hep3B cell proliferation, migration, and invasion by directly targeting COL4A1. Conclusion COL4A1 is negatively regulated by XPD-miR-29a-3p axis and promotes liver cancer progression in vitro (AU)

TWIST1 upregulation affects E-cadherin expression in brain metastases

Purpose E-cadherin is a calcium-dependent glycoprotein whose main role is cell–cell adhesion. Its transcriptional repressor TWIST1 is a basic helix–loop–helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial–mesenchymal transition (EMT)—a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites—breast and lung. Methods The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin–horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations. Results Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p = 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p = 0.034). Conclusion This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment (AU)

Cadherina E y GATA-3 son útiles para confirmar la presencia de conducto deferente en muestras de vasectomía / E-Cadherine and GATA-3 are useful in the confirmation of the vas deferens in vasectomy specimens

INTRODUCCIÓN Y OBJETIVOS: Con frecuencia los urólogos remiten el tejido resecado durante las vasectomías para estudio anatomopatológico con el fin de confirmar la presencia de conducto deferente. El estudio microscópico es sencillo y se suele hacer con hematoxilina-eosina. En ocasiones, se ve dificultado por artefactos de la muestra y la inmunohistoquímica puede ayudar a reconocer la presencia de deferente. MATERIALES Y MÉTODOS: Hemos investigado la utilidad de la determinación inmunohistoquímica de cadherina E y GATA-3 para confirmar epitelio del deferente en 110 secciones de vasectomías con diferentes artefactos, utilizando anticuerpos monoclonales y técnica de multímero conjugado con peroxidasa; 5 arterias y 5 venas renales fueron controles negativos. RESULTADOS: Con cadherina E se observó tinción de membrana moderada (2,7%) o intensa (97,3%) en el epitelio del deferente en todos los casos: 35 sin artefacto, 7 con epitelio denudado, 56 con epitelio comprimido o distorsionado, 8 con epitelio desprendido y 4 con epitelio desplazado. GATA-3 mostró positividad nuclear moderada (31%) o intensa (69%) en todos los casos, incluyendo los 76 con los artefactos señalados. Las arterias y venas fueron negativas para ambos marcadores en el endotelio, con positividad para GATA-3 en ocasionales linfocitos de la pared. CONCLUSIONES: La inmunohistoquímica puede ayudar a reconocer la presencia de epitelio del deferente en vasectomías artefactadas con positividad de membrana para cadherina E y expresión nuclear de GATA-3. El endotelio vascular, por el contrario, es negativo para ambos marcadores. No se debe malinterpretar como positividad la posible tinción para GATA-3 de linfocitos de la pared

INTRODUCTION AND OBJECTIVES: Urologists often submit the resected tissue from vasectomies for histopathological examination in order to confirm the presence of the vas deferens. Microscopy is simple and based on haematoxylin-eosin staining; however, sample artefacts can sometimes cause confusion and immunohistochemistry can be used to identify the vas deferens. MATERIALS AND METHODS: We investigated the utility of immunohistochemical analysis using E-cadherin and GATA-3 to confirm the presence of vas deferens epithelium in 110 vasectomy sections with different artefacts, using monoclonal antibodies and a multimer conjugated with peroxidase based technique; 5 renal arteries and 5 renal veins were stained as negative controls. RESULTS: Membrane staining was observed for E-cadherin, which was moderate (2.7%) or strong (97.3%) in the vas deferens epithelium in all cases: 35 without artefacts, 7 with denuded epithelium, 56 with compressed/distorted epithelium, 8 with detached epithelium and 4 with displaced epithelium. GATA-3 showed moderate (31%) or strong (69%) nuclear staining in all cases, including the 76 with artefacts. In the control group, arteries and veins were negative for both markers in the endothelium, but GATA-3 occasionally stained lymphocytes in the blood vessel wall. CONCLUSIONS: E-cadherin membrane positivity and GATA-3 nuclear expression are useful for the identification of the vas deferens in vasectomy samples containing artefacts. Vascular endothelium is negative for both markers and any possible GATA-3 staining of the lymphocytes in the blood vessel wall should not be misinterpreted

Expresión de E-cadherina y beta-catenina en carcinomas de células escamosas de laringe e hipofaringe / Expression of E-cadherin and Beta-catenin in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

INTRODUCCIÓN Y OBJETIVOS: La disfunción del complejo E-cadherina/catenina está relacionada directamente con la carcinogénesis y el desarrollo de metástasis. El objetivo de este trabajo es investigar el significado pronóstico de la expresión de E-cadherina y beta-catenina en carcinomas de células escamosas de laringe e hipofaringe tratados quirúrgicamente. MATERIAL Y MÉTODOS: Se obtuvieron muestras de tejido tumoral de 133 pacientes consecutivos con carcinomas escamosos de cabeza y cuello (68 de laringe y 65 carcinomas de hipofaringe), que fueron sometidos a tratamiento quirúrgico en nuestro hospital entre 2000 y 2005. La expresión de E-cadherina y beta-catenina se analizó mediante inmunohistoquímica, cuantificando el porcentaje de células teñidas y la intensidad de la tinción. RESULTADOS: La expresión de E-cadherina y beta-catenina fue evaluable en 59 muestras de carcinomas de laringe y en 58 de hipofaringe. En tumores de laringe se observó una asociación significativa entre la baja expresión de beta-catenina de membrana y tumores avanzados T4 y la recidiva tumoral. A nivel de hipofaringe se encontró una asociación significativa de la expresión positiva de Beta-catenina nuclear con pobre diferenciación histológica (p = 0,02). En el análisis multivariante solo la presencia de metástasis ganglionares era factor predictor independiente de disminución de la supervivencia específica para enfermedad en carcinoma de células escamosas de laringe. CONCLUSIONES: La expresión de E-cadherina y beta-catenina no parece tener utilidad pronóstica superior al TNM en los carcinomas epidermoides de laringe e hipofaringe

INTRODUCTION AND OBJECTIVES: Dysfunction of the E-cadherin/catenin complex is directly related to carcinogenesis and metastases development. The aim of this paper is to investigate the prognostic significance of E-cadherin and Beta-catenin expression in surgically treated laryngeal and hypopharyngeal squamous cell carcinomas. MATERIAL AND METHODS: Tumour tissue samples were obtained from 133 consecutive patients with squamous cell carcinomas of the head and neck: 68 of the larynx and 65 hypopharyngeal carcinomas, who underwent surgical treatment in our hospital between 2000 and 2005. E-cadherin and beta-catenin expression was analysed by immunohistochemistry, quantifying the percentage of stained cells and the intensity of staining. RESULTS: E-cadherin and beta-catenin expression was evaluable in 59 laryngeal carcinomas and in 58 cases of hypopharyngeal carcinomas. In the laryngeal tumours, a significant association was found between the low expression of membrane Beta-catenin with T4 tumours and tumour recurrence. In the hypopharynx there was a significant association between positive expression of nuclear beta-catenin and poor histological differentiation (P = .02). In the multivariate analysis, only the presence of lymph node metastases was an independent predictive factor of decreased disease-specific survival in laryngeal squamous cell carcinomas. CONCLUSIONS: The expression of E-cadherin and beta-catenin does not show prognostic significance in laryngeal and hypopharyngeal squamous cell carcinomas over the TNM classification

E-Cadherin gene expression in oral cancer: Clinical and prospective data

Background: Low protein expression of E-cadherin in oral squamous cell carcinoma (OSCC) has been associated with clinical and histopathological traits such as metastases, recurrence, low survival and poor tumor differentiation, and it is considered a high-risk marker of malignancy. However, it is still unknown whether low expression of E-cadherin is also present at the mRNA level in OSCC cases. Objective: The aim of this study was to compare E-cadherin mRNA expression in OSCC patients and controls and to correlate the expression with clinical and prospective characteristics. Material and Methods: Forty patients and 40 controls were enrolled. E-cadherin mRNA expression was evaluated by quantitative real-time polymerase chain reaction using TaqMan probes. Results: E-cadherin mRNA expression was significantly decreased in OSCC patients compared to that of controls (p < 0.001). Whereas no significant association between clinical parameters and E-cadherin expression levels was observed, we noted lower E-cadherin expression levels in patients with positive lymph node metastasis. Conclusions: E-cadherin mRNA expression was markedly diminished in OSCC, in agreement with previous re-sults that examined E-cadherin expression at the protein level. E-cadherin is downregulated in the early clinical stages of OSCC, and its mRNA levels do not change significantly in the advanced stages, suggesting that there is limited usefulness of this parameter for predicting disease progression

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¿Está indicada la gastrectomía profiláctica en pacientes sanos portadores del gen CDH1 para el cáncer gástrico difuso hereditario? / Is prophylactic gastrectomy indicated for healthy carriers of CDH1 gene mutations associated with hereditary diffuse gastric cancer?

Introducción: el cáncer gástrico difuso hereditario (CGDH) constituye uno de los síndromes de cáncer hereditario recientemente comunicados. Aquellos pacientes con sospecha de CGDH deben ser vigilados con endoscopia y toma múltiples de biopsias. Como alternativa, algunos autores proponen la realización de gastrectomía profiláctica (GP) en los portadores de la enfermedad. El objetivo de este trabajo es presentar nuestra experiencia con una familia portadora de la mutación CDH1 a los que se realizó una GP. Pacientes y métodos: nuestro caso índice corresponde a una mujer de 34 años que se diagnosticó de un adenocarcinoma gástrico difuso con carcinomatosis masiva. Presentaba antecedentes familiares de adenocarcinoma gástrico en siete ascendientes. Se realizó un estudio genético mediante secuenciación de CDH1, en el cual se encontró la mutación c1577G>A en el exón 11 del gen CDH1. Resultados: esta mutación estaba también presente en otros seis familiares de la paciente, a los que se les realizó una gastrectomía profiláctica. La anatomía patológica de los estómagos de estos pacientes informó de múltiples focos microscópicos de adenocarcinoma en cinco de ellos, a pesar de que en las numerosas endoscopias realizadas antes de la cirugía no fueron detectados. Conclusiones: recomendamos realizar una gastrectomía profiláctica en los pacientes portadores del gen CDH1 a pesar de ausencia de lesiones tumorales en el screening endoscópico

Introduction: hereditary diffuse gastric cancer (HDGC) is a recently reported hereditary cancer syndrome. Patients with suspected HDGC must be under surveillance via endoscopy and multiple biopsies. As an alternative, some studies suggest prophylactic gastrectomy (PG) for disease carriers. The goal of this article was to report our experience with a CDH1 mutation positive family who underwent PG. Patients and methods: the index case was a 34-year-old female diagnosed with diffuse gastric adenocarcinoma and massive carcinomatosis. There was a family history of gastric adenocarcinoma in seven family members. A genetic study identified the c.1577G>A mutation, in exon 11 of the CDH1 gene via sequencing analysis. Results: this mutation was also present in other six family members, who subsequently underwent prophylactic gastrectomy. The pathology study of resected gastric segments revealed multiple microscopic foci of adenocarcinoma in five of these individuals. These foci were not detected in the multiple endoscopies performed before surgery. Conclusions: we recommend prophylactic gastrectomy for CDH1 mutation carriers even in the absence of lesions during endoscopic screening

Patients with advanced oral squamous cell carcinoma have high levels of soluble E-cadherin in the saliva

Background: The objective of this study was to assess the potential clinical value of the concentration of soluble salivary E-cadherin (sE-cadherin) compared with the clinical value of the presence of membranous E-cadherin (mE-cadherin) in oral squamous cell carcinoma tumor tissues. Material and Methods: Data regarding patient demographics, clinical stage, saliva and tumor tissue samples were collected. The saliva was analyzed for sE-cadherin protein levels and was compared to the mE-cadherin immunohistochemical expression levels in tumor tissues, which were assessed via the HercepTest(R) method. Patients without cancer were included in the study as a control group for comparisons of the sE-cadherin levels. Results: sE-cadherin levels in the saliva of patients without cancer were lower than those in patients with cancer, and the difference was statistically significant (p=0.031). Low mE-cadherin expression was statistically significantly associated with lymph node positivity (p=0.015) and advanced clinical stage (p=0.001). The inverse relationship between mE-cadherin and sE-cadherin was significant in terms of lymph node positivity (p=0.014) and advanced clinical stage (p=0.037). Conclusions: The results suggest that sE-cadherin levels are significantly increased in patients with oral cancer and that its low expression within the membrane as well as the progression of the disease appear to be inversely associated with levels of sE-cadherin in the saliva (AU)

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IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1+/-, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage (AU)

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Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas

BACKGROUND: This study aimed to compare the histological and immunohistochemical characteristics of ameloblastomas (AM) and ameloblastic carcinomas (AC). MATERIAL AND METHODS: Fifteen cases of AM and 9 AC were submitted to hematoxilin and eosin (H&E) and immunohistochemical analysis with the following antibodies: cytokeratins 5,7,8,14 and 19, Ki-67, p53, p63 and the cellular adhesion molecules CD138 (Syndecan-1), E-cadherin and β-catenin. The mean score of the expression of Ki-67 and p53 labelling index (LIs) were compared between the groups using the t test. A value of p < 0.05 was considered to be statistically significant. RESULTS: All cases were positive for CKs 5, 14 and 19, but negative for CKs 7 and 8. CKs 5 and 19 were positive mainly in the central regions of the ameloblastic islands, while the expression in AC was variable in intensity and localization. CK14 was also variably expressed in both AM and AC. Ki-67 (P=.001) and p53 (P=.004) immunoexpression was higher in AC. All cases were positive for p63, but values were higher in AC. CD138 was mainly expressed in peripheral cells of AM, with a weak positivity in the central areas, while it was positive in most areas of ACs, except in less differentiated regions, where expression was decreased or lost. E-cadherin and β-catenin were weakly positive in both AM and AC. CONCLUSIONS: These results shows that Ki-67, p53 and p63 expression was higher in AC as compared to AM, suggesting that these markers can be useful when considering diagnosis of malignancy, and perhaps could play a role in malignant transformation of AM. Pattern of expression of CKs 5 and 19 in AC were different to those found in AM, suggesting genetic alterations of these proteins in malignant cells. It was confirmed that CK19 is a good marker for benign odontogenic tumors, such as AM, but it is variably expressed in malignant cases

La expresión de microARN-133 inhibe la transición epitelio-mesenquimatosa en las células del cáncer de pulmón apuntando directamente al FOXQ1 / Expression of microRNA-133 inhibits epithelial-mesenchymal transition in lung cancer cells by directly targeting FOXQ1

Introducción: El microARN (miR) se ha relacionado con la génesis tumoral en muchos tipos de cáncer, pero ningún estudio ha examinado el rol exacto del miR-133 en el cáncer de pulmón. Métodos: Identificamos el miR-133 como posible regulador de la expresión de la FOXQ1 e investigamos la posible implicación del miR-133 en la migración y la invasión de células de cáncer de pulmón, y el mecanismo molecular subyacente. Resultados: El miR-133 se dirigió directamente y redujo la expresión de la FOXQ1, que a su vez redujo la concentración de TGF-β. El miR-133 disminuyó en líneas celulares de cáncer de pulmón A549 y HCC827, y su reexpresión inhibió significativamente la migración y la invasión de células de cáncer de pulmón. Investigaciones subsiguientes revelaron que dicha inhibición estaba provocada por una inversión de la transición epitelio-mesenquimatosa, constatada por una elevación del marcador epitelial E-cadherina inducida por el miR-133 y una reducción del marcador vimentina. Conclusiones: Nuestro estudio es el primero que ha identificado el miR-133 como biomarcador del cáncer de pulmón. Su función es reducir la FOXQ1 e inhibir la transición epitelio-mesenquimatosa, la cual antagoniza la génesis tumoral en el cáncer de pulmón. Por consiguiente, nuestros datos respaldan el papel del miR-133 como posible instrumento terapéutico molecular en el tratamiento del cáncer de pulmón

Introduction: MicroRNA (miR) was implicated in the tumorigenesis of many types of cancer, but no study was conducted on the exact role of miR-133 in lung cancer. Methods: We have identified miR-133 as a putative regulator of FOXQ1 expression, and investigated the potential involvement of miR-133 in the migration and invasion of lung cancer cells, as well as the underlying molecular mechanism. Results: MiR-133 directly targeted and down-regulated FOXQ1 expression, which in turn reduced TGF-β level. MiR-133 was down-regulated in lung cancer cell lines A549 and HCC827, and its re-expression significantly inhibited the migration and invasion of the lung cancer cells. Further investigation revealed that this inhibition was caused by reversing the epithelial-mesenchymal transition, evidenced by miR-133 induced elevation of epithelial marker E-cadherin, and reduction of mesenchymal marker Vimentin. Conclusions: Our study is the first to identify miR-133 as a biomarker for lung cancer. It functions to down-regulate FOXQ1, and inhibit epithelial mesenchymal transition, which antagonizes lung cancer tumorigenesis. Therefore our data support the role of miR-133 as a potential molecular therapeutic tool in treating lung cancer

Acantholytic squamous cell carcinoma arising in actinic keratoacanthoma: Two cases with E-cadherin expression supporting a potentially different prognosis / Carcinoma de células escamosas acantolítico originado en queratoacantoma actínico: dos casos con expresión de E-cadherina indicando un pronóstico diferente

Among crateriform squamous proliferation, keratoacanthoma is considered as a squamous cell carcinoma or as a non-malignant, self-healing lesion that frequently becomes malignant. To date, published cases of neoplasms originating from keratoacanthoma are always conventional squamous cell carcinomas. Acantholytic squamous cell carcinoma arising in keratoacanthomas has not been previously reported. We present two crater-shaped nodular lesions on the face of elderly patients with clinical and histopathological features of keratoacanthoma with transformation areas to acantholytic squamous cell carcinoma. In the immunohistochemical study, Ki-67 and p63 immunostaining supports the diagnosis of acantholytic squamous cell carcinoma ex-keratoacanthoma. We suggest that E-cadherin expression and vimentin negativity could probably be related with less aggressive behaviour and a better prognosis (AU)

Dentro de las proliferaciones escamosas crateriformes, el queratoacantoma se considera como un carcinoma escamoso o como una lesión benigna autocurativa que frecuentemente se vuelve maligna. Las neoplasias descritas que se originan del queratoacantoma son siempre carcinomas escamosos convencionales. Carcinomas escamosos acantolíticos originados en queratoacantomas no se han descrito en la literatura. Presentamos 2 nódulos crateriformes en la cara de ancianos con características clínicas e histopatológicas de queratoacantoma con áreas de transformación a carcinoma escamoso acantolítico. En el estudio inmunohistoquímico, la expresión de Ki-67 y p63 apoya el diagnóstico de carcinoma escamoso acantolítico ex-queratoacantoma. Nosotros hipotetizamos que la expresión de E-cadherina y la negatividad de vimentina están probablemente relacionadas con menor agresividad y excelente pronóstico en estos pacientes (AU)

MicroRNA-10b indicates a poor prognosis of non-small cell lung cancer and targets E-cadherin

Background. MicroRNA-10b(miR-10b) has been reported to be dysregulated in some types of cancer and to play an important role in invasion and metastasis. It was previously found to be a tumor enhancer in NSCLC; however, its clinical significance in NSCLC has not been evaluated. Methods. We compared the expression levels of miR-10b in 73 pairs of NSCLC tissues and the corresponding noncancerous tissues, as well as in human lung cancer cell line A549 and NHBE cell line by qRT-PCR. Expression of E-cadherin (E-cad) was detected using RT-PCR and Western blot analysis. The disease-specific survival (DSS) was analyzed by log-rank test, and survival curves were plotted according to Kaplan–Meier. Results. MiR-10b was significantly upregulated in NSCLC tissues as well as in A549 cell line. The relative miR-10b expression levels were significantly positively correlated with TNM stage (p = 0.01) and regional lymph node involvement (p < 0.001). Kaplan–Meier analysis showed that patients with higher levels of miR-10b had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year DSS of 29.5 and 63.8 %, respectively (p = 0.003). The E-cad mRNA and protein were overexpressed in miR-10b-suppressed cells compared with controls. Conclusion. Our results indicated that miR-10b expression was an independent prognostic factor in NSCLC patients. Furthermore, miR-10b might be necessary for driving the expression of E-cad in NSCLC (AU)

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Tumor necrosis factor-alpha-induced microvascular endothelial cell hyperpermeability: role of intrinsic apoptotic signaling

Tumor necrosis factor-alfa (TNF-alfa), a pro-apoptotic cytokine, is involved in vascular hyperpermeability, tissue edema, and inflammation. We hypothesized that TNF-alfa induces microvascular hyperpermeability through the mitochondria-mediated intrinsic apoptotic signaling pathway. Rat lung microvascular endothelial cells grown on Transwell inserts, chamber slides, or dishes were treated with recombinant TNF-alfa (10 ng/ml) in the presence or absence of a caspase-3 inhibitor, Z-DEVD-FMK (100 μM). Fluorescein isothiocyanate (FITC)-albumin (5 mg/ml) was used as a marker of monolayer permeability. Mitochondrial reactive oxygen species (ROS) was determined using dihydrorhodamine 123 and mitochondrial transmembrane potential using JC-1. The adherens junction integrity and actin cytoskeletal organization were studied using β-catenin immunofluorescence and rhodamine phalloidin, respectively. Caspase-3 activity was measured fluorometrically. The pretreatment with Z-DEVD-FMK (100 μM) attenuated TNF-alfa-induced (10 ng/ml) disruption of the adherens junctions, actin stress fiber formation, increased caspase-3 activity, and monolayer hyperpermeability (p < 0.05). TNF-alfa (10 ng/ml) treatment resulted in increased mitochondrial ROS formation and decreased mitochondrial transmembrane potential. Intrinsic apoptotic signaling-mediated caspase-3 activation plays an important role in regulating TNF-α-induced endothelial cell hyperpermeability

Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal junction adenocarcinoma

PURPOSE: The poor prognosis of gastroesophageal junction (GEJ) adenocarcinoma is largely associated with metastasis. We here report the first study to investigate the expression of epithelial-mesenchymal transition (EMT) markers Snail1 and E-cadherin in GEJ adenocarcinoma. METHODS: Snail1 and E-cadherin were detected by immunohistochemistry in a cohort of 128 patients with surgically resected GEJ adenocarcinoma. We assessed the pathologic and prognostic relevance in all patients and within clinically different preserved E-cadherin and reduced E-cadherin-expressing sub-groups. RESULTS: Immunoreactivity for Snail1 and E-cadherin was positive in 68 and 43 % of tumors, respectively. Snail1-positive tumors had more frequent lymph node metastasis and advanced tumor stage. E-cadherin expression was highly associated with histological differentiation, tumor size, advanced stage, presence of lymph node metastasis and distant metastasis. Patients with positive E-cadherin expression or negative Snail1 expression had significantly favorable overall survival rate. In E-cadherin-preserved tumors, the expression of Snail1 was related to lymph node metastasis, advanced stage and poor patient outcome. However, Snail1 expression had no statistically significant relationship with clinicopathologic parameters or prognosis in the reduced E-cadherin-expressing sub-group. Multivariate survival analysis identified that tumor stage [hazard ratio (HR) 2.440; 95 % confidence interval (CI) 1.216-4.896; P = 0.012], lymph node metastasis (HR 2.404; 95 % CI 1.188-4.867; P = 0.015) and gender (HR 3.244; 95 % CI 1.568-6.714; P = 0.002) were independent prognostic markers for overall survival. CONCLUSIONS: Snail1 may act more critically in E-cadherin-positive tumors. Evaluation of Snail1 and E-cadherin in GEJ adenocarcinoma may help in assessing malignant properties and stratifying patients (AU)

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