The Journal of pathology
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The Journal of pathology · Nov 2003
ReviewPathogenetic mechanisms in usual interstitial pneumonia/idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive, usually fatal, form of interstitial lung disease characterized by failure of alveolar re-epithelialization, persistence of fibroblasts/myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which ultimately results in respiratory failure. Clinical IPF is associated with a histopathological pattern of usual interstitial pneumonia (UIP) on surgical lung biopsy. Therapy for this disease with glucocorticoids and other immunomodulatory agents is largely ineffective and recent trials of newer anti-fibrotic agents have been disappointing. ⋯ Unlike other fibrotic diseases of the lung, such as those associated with collagen vascular disease, occupational exposure, or chemotherapeutic agents, UIP is not associated with a significant inflammatory response; rather, dysregulated epithelial-mesenchymal interactions predominate. Identification of pathways crucial to fibrogenesis might offer potentially novel therapeutic targets to slow or halt the progression of IPF. This review focuses on evolving concepts of cellular and molecular mechanisms in the pathogenesis of UIP/IPF.
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The Journal of pathology · Sep 2003
Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants.
Intestinal inflammation is accompanied by excessive production of reactive oxygen and nitrogen metabolites. In order to counteract their harmful effects, the intestinal mucosa contains an extensive system of antioxidants. It has previously been shown that the levels of and the balance between the most important antioxidants are seriously impaired within the intestinal mucosa from inflammatory bowel disease (IBD) patients compared with normal mucosa. ⋯ In CD, lipid peroxidation was independently associated with the concentration of metallothionein and with Mn-superoxide dismutase activity, suggesting the involvement of hydroxyl radicals and superoxide anions. In UC, however, the amount of MDA was associated with epithelial catalase expression and neutrophilic myeloperoxidase activity, suggesting a hydrogen peroxide- and/or hypochlorous acid-mediated mechanism. The present study underlines the importance of oxidative stress in the pathogenesis of IBD and provides clues regarding the (anti)oxidants involved which indicate that this process evolves through diverging pathways in CD and UC.
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The Journal of pathology · Sep 2003
Abstracts of the 2nd joint meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain and Ireland, and the 185th meeting of the Pathological Society of Great Britain and Ireland. 1-4 July 2003, Bristol, United Kingdom.
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The Journal of pathology · Jun 2003
The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression.
Angiogenesis is essential for tumour growth and metastasis. It is controlled by angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF)-A. Although its role has been demonstrated in many tumour types including colorectal carcinoma (CRC), the importance of the newer family members in adenoma, invasive tumour growth, and progression to a metastatic phenotype has been poorly characterized in CRC. ⋯ VEGFR-1 was significantly correlated with tumour grade (p = 0.02), Duke's stage (p < 0.001), and lymph node involvement (p = 0.004), VEGFR-2 with lymph node involvement (p = 0.02), and VEGFR-3 did not correlate with any of the clinicopathological variables tested. These results suggest that VEGF-A and VEGF-B play a role early in tumour development at the stage of adenoma formation and that VEGF-C plays a role in advanced disease when there is more likelihood of metastatic spread. The finding of increased levels of VEGF-A and VEGF-D expression in normal tissues collected from a site distant from the primary tumour indicates changes in the surrounding tumour environment that may enhance the subsequent spread of tumour cells.
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The Journal of pathology · May 2003
Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer--association with tumour cell proliferation.
The mitotic spindle assembly checkpoint modulates the timing of anaphase initiation in response to improper alignment of chromosomes at the metaphase plate. The BUB gene family encodes proteins which are part of a large multi-protein kinetochore complex and which are believed to be key components of the checkpoint regulatory pathway. Failure of this surveillance system can lead to genomic instability and could be responsible for the increased incidence of aneuploidy in gastric cancer. ⋯ These results suggest that inactivation of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 by epigenetic silencing does not seem to play a role in gastric carcinogenesis. The strong correlation of BUB expression level and tumour cell proliferation suggests that BUB overexpression is a proliferation-dependent phenomenon in gastric cancer. However, overexpression due to lack of normal BUB protein function or due to a yet unknown additional BUB function has to be considered.