46 research outputs found
Helicobacter pylori Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis
(1) Background: Persistent Helicobacter pylori infection is the most important risk factor for
gastric cancer. The urokinase receptor (uPAR) is upregulated in lesions harboring cancer invasion
and inflammation. Circumstantial evidence tends to correlate H. pylori colonization with increased
uPAR expression in the human gastric epithelium, but a direct causative link has not yet been
established in vivo; (2) Methods: In a mouse model of H. pylori-induced gastritis, we investigated
the temporal emergence of uPAR protein expression in the gastric mucosa in response to H. pylori
(SS1 strain) infection; (3) Results: We observed intense uPAR immunoreactivity in foveolar epithelial
cells of the gastric corpus due to de novo synthesis, compared to non-infected animals. This uPAR
induction represents a very early response, but it increases progressively over time as do infiltrating
immune cells. Eradication of H. pylori infection by antimicrobial therapy causes a regression of
uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by
prostaglandin E2 treatment attenuates uPAR expression. Notwithstanding this relationship, H. pylori
does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We
showed that persistent H. pylori colonization is a necessary event for the emergence of a relatively
high uPAR protein expression in murine gastric epithelial cells.Danish Cancer Society/[R2-A261-09-S2]//DinamarcaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Estructuras Microscópicas (CIEMIC
International consensus guidelines for scoring the histopathological growth patterns of liver metastasis
BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. RESULTS: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). CONCLUSIONS: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies
Mental health and school dropout across educational levels and genders: a 4.8-year follow-up study
Expression of uPAR in tumor-associated stromal cells is associated with colorectal cancer patient prognosis: a TMA study
Discrimination of different forms of the murine urokinase plasminogen activator receptor on the cell surface using monoclonal antibodies
uPAR as anti-cancer target:evaluation of biomarker potential, histological localization, and antibody-based therapy
uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy
Validation of a fast and traceable radiographic scale calibration of dimensional computed tomography
Social inequality in type 2 diabetes mellitus in the Faroe Islands: a cross-sectional study
Tissue Inhibitor of Metalloproteinase-1 Is Confined to Tumor-Associated Myofibroblasts and Is Increased With Progression in Gastric Adenocarcinoma
The tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the extracellular matrix–degrading activity of several matrix metalloproteinases, thereby regulating cancer cell invasion and metastasis. Studies describing the expression pattern and cellular localization of TIMP-1 in gastric cancer are, however, highly discordant. We addressed these inconsistencies by performing immunohistochemistry and in situ hybridization analyses in a set of 49 gastric cancer lesions to reexamine the TIMP-1 localization. In addition, we correlated these findings to clinicopathological parameters. We show that strong expression of TIMP-1 protein and mRNA was observed in a subpopulation of stromal fibroblast-like cells at the periphery of the cancer lesions. In a few cases, a small fraction of cancer cells showed weak expression of TIMP-1 protein and mRNA. The stromal TIMP-1-expressing cells were mainly tumor-associated myofibroblasts. In the normal-appearing mucosa, scattered TIMP-1 protein was only found in chromogranin A positive cells. TIMP-1-positive myofibroblasts at the invasive front of the tumors were more frequently seen in intestinal than in diffuse histological subtype cases (p=0.009). A significant trend to a higher number of cases showing TIMP-1 staining in myofibroblasts with increasing tumor, node, metastasis (TNM) stage was also revealed (p=0.041). In conclusion, tumor-associated myofibroblasts are the main source of increased TIMP-1 expression in gastric cancer.Danish Cancer Society/[R2-A261-09-S2]//EuropaEuropean Community’s Seventh Framework Program/[201279]/FP7/EuropaAxel Muusfeldts Fond/[]//EuropaKrista og Viggo Petersens Fond/[]/KV/EuropaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Estructuras Microscópicas (CIEMIC