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1.
Proc Natl Acad Sci U S A ; 112(31): E4264-71, 2015 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-26195794

RESUMEN

Intestinal epithelial cells contribute to regulation of intestinal immunity in mammals, but the detailed molecular mechanisms of such regulation have remained largely unknown. Stomach-cancer-associated protein tyrosine phosphatase 1 (SAP-1, also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10-deficient mice, a model of inflammatory bowel disease, resulted in a marked increase in the severity of colitis in association with up-regulation of mRNAs for various cytokines and chemokines in the colon. Tyrosine phosphorylation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific transmembrane protein of the Ig superfamily, was greatly increased in the intestinal epithelium of the SAP-1-deficient animals, suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in cultured cells through the activation of nuclear factor-κB (NF-κB). In addition, SAP-1 and CEACAM20 were found to form a complex through interaction of their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through which the intestinal epithelium contributes to intestinal immunity.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Colitis/enzimología , Colitis/prevención & control , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Animales , Recuento de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Colitis/patología , Colon/patología , Femenino , Células Caliciformes/metabolismo , Células Caliciformes/patología , Células HEK293 , Humanos , Interleucina-10/deficiencia , Interleucina-10/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones , FN-kappa B/metabolismo , Fosforilación , Fosfotirosina/metabolismo , Unión Proteica , Transporte de Proteínas , Proteínas Tirosina Quinasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/deficiencia , Quinasa Syk , Dominios Homologos src , Familia-src Quinasas/metabolismo
2.
Cureus ; 16(7): e63873, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39100020

RESUMEN

OBJECTIVES: This study aimed to leverage Visually AcceSAble Rembrandt Images (VASARI) radiological features, extracted from magnetic resonance imaging (MRI) scans, and machine-learning techniques to predict glioma grade, isocitrate dehydrogenase (IDH) mutation status, and O6-methylguanine-DNA methyltransferase (MGMT) methylation. METHODOLOGY: A retrospective evaluation was undertaken, analyzing MRI and molecular data from 107 glioma patients treated at a tertiary hospital. Patients underwent MRI scans using established protocols and were evaluated based on VASARI criteria. Tissue samples were assessed for glioma grade and underwent molecular testing for IDH mutations and MGMT methylation. Four machine learning models, namely, Random Forest, Elastic-Net, multivariate adaptive regression spline (MARS), and eXtreme Gradient Boosting (XGBoost), were trained on 27 VASARI features using fivefold internal cross-validation. The models' predictive performances were assessed using the area under the curve (AUC), sensitivity, and specificity. RESULTS: For glioma grade prediction, XGBoost exhibited the highest AUC (0.978), sensitivity (0.879), and specificity (0.964), with f6 (proportion of non-enhancing) and f12 (definition of enhancing margin) as the most important predictors. In predicting IDH mutation status, XGBoost achieved an AUC of 0.806, sensitivity of 0.364, and specificity of 0.880, with f1 (tumor location), f12, and f30 (perpendicular diameter to f29) as primary predictors. For MGMT methylation, XGBoost displayed an AUC of 0.580, sensitivity of 0.372, and specificity of 0.759, highlighting f29 (longest diameter) as the key predictor. CONCLUSIONS: This study underscores the robust potential of combining VASARI radiological features with machine learning models in predicting glioma grade, IDH mutation status, and MGMT methylation. The best and most balanced performance was achieved using the XGBoost model. While the prediction of glioma grade showed promising results, the sensitivity in discerning IDH mutations and MGMT methylation still leaves room for improvement. Follow-up studies with larger datasets and more advanced artificial intelligence techniques can further refine our understanding and management of gliomas.

3.
BMJ Open ; 13(8): e071324, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37553193

RESUMEN

INTRODUCTION: The dentomaxillofacial (DMF) area, which includes the teeth, maxilla, mandible, zygomaticum, orbits and midface, plays a crucial role in the maintenance of the physiological functions despite its susceptibility to fractures, which are mostly caused by mechanical trauma. As a diagnostic tool, radiographic imaging helps clinicians establish a diagnosis and determine a treatment plan; however, the presence of human factors in image interpretation can result in missed detection of fractures. Therefore, an artificial intelligence (AI) computing system with the potential to help detect abnormalities on radiographic images is currently being developed. This scoping review summarises the literature and assesses the current status of AI in DMF fracture detection in diagnostic imaging. METHODS AND ANALYSIS: This proposed scoping review will be conducted using the framework of Arksey and O'Malley, with each step incorporating the recommendations of Levac et al. By using relevant keywords based on the research questions. PubMed, Science Direct, Scopus, Cochrane Library, Springerlink, Institute of Electrical and Electronics Engineers, and ProQuest will be the databases used in this study. The included studies are published in English between 1 January 2000 and 30 June 2023. Two independent reviewers will screen titles and abstracts, followed by full-text screening and data extraction, which will comprise three components: research study characteristics, comparator and AI characteristics. ETHICS AND DISSEMINATION: This study does not require ethical approval because it analyses primary research articles. The research findings will be distributed through international conferences and peer-reviewed publications.


Asunto(s)
Inteligencia Artificial , Fracturas Óseas , Humanos , Revisión por Pares , Proyectos de Investigación , Literatura de Revisión como Asunto
4.
Genes Cells ; 15(5): 513-24, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20398064

RESUMEN

Post-translational modification of protein tyrosine phosphatases (PTPs) is implicated in functional modulation of these enzymes. Stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1), as well as protein tyrosine phosphatase receptor type O (PTPRO) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) are receptor-type PTPs (RPTPs), which belong to the R3 subtype RPTP family. Here, we have shown that the carboxyl (COOH)-terminal region of SAP-1 undergoes tyrosine phosphorylation by the treatment with a PTP inhibitor. Src family kinases are important for the tyrosine phosphorylation of SAP-1. Either Grb2 or Fyn, through their Src homology-2 domains, bound to the tyrosine-phosphorylated SAP-1. Moreover, both PTPRO and VE-PTP underwent tyrosine phosphorylation in their COOH-terminal regions. Tyrosine phosphorylation of VE-PTP or PTPRO also promoted their complex formations with Grb2 or Fyn. Forced expression of SAP-1, PTPRO or VE-PTP promoted cell spreading and lamellipodium formation of fibroblasts that expressed an activated form of Ras. In contrast, such effects of non-tyrosine-phosphorylated forms of these RPTPs were markedly smaller than those of wild-type RPTPs. Our results thus suggest that tyrosine phosphorylation of R3 subtype RPTPs promotes their complex formations with Grb2 or Fyn and thus participates in the regulation of cell morphology.


Asunto(s)
Proteína Adaptadora GRB2/metabolismo , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Tirosina/metabolismo , Secuencias de Aminoácidos , Animales , Línea Celular , Proteína Adaptadora GRB2/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Fosforilación , Proteínas Proto-Oncogénicas c-fyn/genética , Seudópodos/metabolismo , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética , Tirosina/genética
5.
Genes Cells ; 15(12): 1189-200, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21040253

RESUMEN

Mononuclear phagocytes such as dendritic cells (DCs) and macrophages in the lamina propria (LP) are thought to be important for both induction of inflammatory responses and maintenance of immunologic tolerance in the mammalian intestine. The molecular mechanisms by which these cells regulate intestinal immunity have remained poorly understood, however. Signal regulatory protein α (SIRPα) is a transmembrane protein that is specifically expressed in DCs, macrophages and neutrophils. Here, we show that SIRPα is abundant in CD11c(+) CD11b(+) LP cells of the mouse intestine. Whereas SIRPα did not appear to be important for the steady-state homeostasis of mucosal immunity in the intestine, the flagellin-stimulated production of IL-17 or interferon (IFN)-γ by LP cells of SIRPα mutant (MT) mice that lack the cytoplasmic region of the protein was markedly decreased compared with that observed with wild-type cells. Moreover, the flagellin-induced production of IL-6 by LP cells from SIRPα MT mice was also greatly reduced. SIRPα MT mice were also resistant to the development of colitis induced by IL-10 deficiency. Our data thus suggest that SIRPα expressed on CD11c(+) LP cells is important for the production of IL-17 or IFN-γ in the LP as well as for the development of colitis induced by IL-10 deficiency.


Asunto(s)
Inmunidad Mucosa/inmunología , Intestinos/inmunología , Receptores Inmunológicos/inmunología , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Membrana Mucosa/inmunología , Receptores Inmunológicos/genética
6.
Genes Cells ; 14(3): 295-308, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19170756

RESUMEN

SAP-1 (PTPRH) is a receptor-type protein tyrosine phosphatase (RPTP) with a single catalytic domain in its cytoplasmic region and fibronectin type III-like domains in its extracellular region. The cellular localization and biological functions of this RPTP have remained unknown, however. We now show that mouse SAP-1 mRNA is largely restricted to the gastrointestinal tract and that SAP-1 protein localizes to the microvilli of the brush border in gastrointestinal epithelial cells. The expression of SAP-1 in mouse intestine is minimal during embryonic development but increases markedly after birth. SAP-1-deficient mice manifested no marked changes in morphology of the intestinal epithelium. In contrast, SAP-1 ablation inhibited tumorigenesis in mice with a heterozygous mutation of the adenomatous polyposis coli gene. These results thus suggest that SAP-1 is a microvillus-specific RPTP that regulates intestinal tumorigenesis.


Asunto(s)
Adenoma/metabolismo , Neoplasias Intestinales/metabolismo , Intestino Delgado/metabolismo , Microvellosidades/metabolismo , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Adenoma/patología , Animales , Epitelio/metabolismo , Epitelio/patología , Genes APC , Neoplasias Intestinales/patología , Intestino Delgado/patología , Ratones , Ratones Noqueados , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética
7.
Clin Case Rep ; 8(12): 3178-3183, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33363902

RESUMEN

Metastatic breast cancer may present as a pericardial effusion that can progress to a life-threatening cardiac tamponade. Pericardial window followed by initial chemotherapy needs to be immediately applied in order to achieve a favorable outcome.

8.
Pathology ; 37(3): 211-5, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16175893

RESUMEN

AIM: Hepatoid adenocarcinoma, a putative chemosensitive tumour, is defined as a tumour with aberrant hepatocellular differentiation occurring in extrahepatic organs such as the stomach, usually in the gastrointestinal tract. Differentiation in the hepatocellular direction is usually supported by the production of alpha-fetoprotein (AFP) and, more recently, albumin (ALB) mRNA. We investigated ALB mRNA to address whether adenocarcinoma with hepatoid morphology, regardless of AFP production, can be diagnosed solely by morphological criteria as a hepatoid adenocarcinoma. METHODS: We performed in situ hybridisation (ISH) and immunohistochemistry (IH) for ALB mRNA on AFP-negative gastric adenocarcinomas with hepatoid morphology. AFP-positive hepatoid adenocarcinomas and AFP-negative conventional gastric adenocarcinomas were also investigated as positive and negative controls, respectively. RESULTS: All three gastric adenocarcinomas with hepatoid morphology with no evidence of AFP production stained positive for ALB mRNA, thus providing evidence of differentiation in the hepatocellular direction. Three of five cases of AFP-positive hepatoid adenocarcinoma of the stomach were positive for ALB mRNA, while 11 cases of AFP-negative conventional gastric adenocarcinoma were negative. CONCLUSION: The present study demonstrates that, irrespective of AFP production, gastric adenocarcinoma with morphological patterns suggestive of hepatoid differentiation should be diagnosed as hepatoid adenocarcinoma with important prognostic implications.


Asunto(s)
Adenocarcinoma/patología , Albúminas/biosíntesis , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/patología , Neoplasias Gástricas/patología , alfa-Fetoproteínas/biosíntesis , Adenocarcinoma/metabolismo , Carcinoma Hepatocelular/metabolismo , Diagnóstico Diferencial , Hepatocitos/patología , Humanos , Inmunohistoquímica , Hibridación in Situ , ARN Mensajero/análisis , ARN Neoplásico/análisis , Neoplasias Gástricas/metabolismo
9.
Exp Mol Pathol ; 82(3): 316-21, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16904665

RESUMEN

Alpha-fetoprotein (AFP)-producing gastric cancer (AFP-GC) is a highly malignant variant of adenocarcinoma with aberrant hepatocellular phenotype. A detailed understanding of the regulation of its liver phenotype is lacking. Liver-enriched nuclear factors (LENFs) are implicated in the transcriptional regulation of AFP in the fetal liver. To investigate the regulatory role of LENFs in AFP-GCs, the expression of LENFs including CCAAT/enhancer binding protein (C/EBP)-beta, C/EBP-alpha, hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta and HNF-4alpha was investigated in 3 cell lines of AFP-GC and 7 cell lines of control GC. The liver activating protein (LAP), an activating isoform of C/EBP-beta, was predominantly expressed in AFP-GCs, whereas the liver inhibitory protein (LIP), an inhibitory isoform of C/EBP-beta, predominated in the control GCs. HNF-1alpha was relatively suppressed in AFP-GCs. HNF-4alpha was expressed in one of three AFP-GC cell lines. C/EBP-alpha and HNF-1beta were expressed at the same levels in both cell types of GC. AFP-GCs expressed a set of hepatocyte-related proteins (e.g., transferrin and albumin) while they still retained the several glandular cell-related proteins (e.g., MUC2). The induction of LIP reduced transferrin expression and induced CEA expression in an AFP-GC line. Collecting these results, it was suggested that the contribution of LENFs, especially isoforms of C/EBP-beta, is possibly important in phenotypic regulation of AFP-GCs.


Asunto(s)
Adenocarcinoma/metabolismo , Factores Nucleares del Hepatocito/biosíntesis , Neoplasias Gástricas/metabolismo , alfa-Fetoproteínas/biosíntesis , Western Blotting , Línea Celular Tumoral , Humanos , Isoformas de Proteínas/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección
10.
Int J Gynecol Pathol ; 22(3): 266-71, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12819394

RESUMEN

Hepatoid carcinoma of the ovary is an ovarian carcinoma that has phenotypic properties in common with hepatocellular carcinomas. However, the extent of the tumor cells' similarity to and their difference from hepatocytes is largely unknown. In addition, the precursor cell of origin for hepatoid carcinoma of the ovary has not been identified. Three cases of alpha-fetoprotein-producing hepatoid carcinoma of the ovary that were admixed with an adenocarcinoma of common surface epithelial type are reported. The hepatoid carcinomas had a trabecular architecture with canaliculi detected by polyclonal (but not monoclonal) anticarcinoembryonic antigen antibodies. A hepatic phenotype in the hepatoid tumor cells was further supported by the production of albumin mRNA by in situ hybridization. The adenocarcinomas in the three cases were mucinous (Case 1), serous (Case 2), and endometrioid (Case 3), respectively. The cytokeratin (CK) profile in both the hepatoid and adenocarcinomatous components was CK18+/CK19+/CK20+/-, whereas normal and neoplastic hepatocytes were CK18+/CK19-/CK20-. Although this study supports a hepatic phenotype in ovarian hepatoid carcinoma, the CK profile of hepatoid carcinoma differs from that of normal and neoplastic hepatocytes but resembles that of the associated common epithelial adenocarcinoma. These findings suggest that hepatoid carcinoma of the ovary is probably derived from carcinomas of surface epithelial origin by a process of neometaplasia or transdifferentiation.


Asunto(s)
Adenocarcinoma/patología , Neoplasias Ováricas/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Adenocarcinoma Mucinoso/patología , Anciano , Albúminas/genética , Antígeno Ca-125/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma Endometrioide/patología , Carcinoma Hepatocelular , Cistadenocarcinoma Seroso/patología , Femenino , Hepatocitos , Humanos , Hibridación in Situ , Japón , Neoplasias Hepáticas , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , ARN Mensajero/análisis , alfa-Fetoproteínas/biosíntesis
11.
Mod Pathol ; 15(12): 1326-32, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12481014

RESUMEN

The classification of thymic epithelial tumors is controversial because prediction of the biological behavior of these tumors from their morphologic appearance is difficult. The aim of this study was to evaluate the proliferative activity and rate of apoptosis of thymic epithelial tumors classified according to World Health Organization histological classification. We also attempted to determine the importance of a number of proapoptotic factors in these processes. We investigated 46 surgically resected thymic epithelial tumors (8 Type A, 8 Type AB, 7 Type B1, 7 Type B2, 6 Type B3, and 10 Type C). Immunohistochemical staining was performed to determine the tumor expression of p53 protein, Bax, Bcl-2, and survivin. In addition, the Ki-67 labeling index (LI) and apoptotic index (AI) of these tumors were evaluated. Type C thymoma had a higher LI (16.55 +/- 12.12%) than did the other histological subtypes. Stage IV thymoma (12.36 +/- 9.99%) had a higher LI than did Stage I tumor. The AI was significantly elevated in Type B1 thymoma (1.47 +/- 0.55%). Overexpression of p53 protein was observed in Type B3 and C thymomas. p53 protein-positive tumors had a higher LI than did p53 protein-negative tumors (P <.0001). Bcl-2 expression was observed in Type A, AB, and C thymomas. Bcl-2-positive thymoma had a lower AI than did Bcl-2-negative thymoma (P =.0157). These results suggest that overexpression of p53 protein is associated with a higher tumor proliferative activity and that Bcl-2 acts as an inhibitor of apoptosis in thymoma. Bcl-2 and p53 protein expression may be useful markers in differentiating thymoma subtypes.


Asunto(s)
Apoptosis , Timoma/patología , Neoplasias del Timo/patología , Adulto , Anciano , Anciano de 80 o más Años , División Celular , Femenino , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Proteínas Inhibidoras de la Apoptosis , Antígeno Ki-67/análisis , Masculino , Proteínas Asociadas a Microtúbulos/análisis , Persona de Mediana Edad , Proteínas de Neoplasias , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Survivin , Timoma/metabolismo , Neoplasias del Timo/metabolismo , Proteína p53 Supresora de Tumor/análisis , Proteína X Asociada a bcl-2
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