Coordinated Increased Expression of Cyclooxygenase2 and Nuclear Factor κB Is a Steady Feature of Urinary Bladder Carcinogenesis

Objectives. The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF-κB immunohistochemical expression in a large series of normal epithelium and bladder carcinomas. Methods. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females with bladder carcinomas). Results. COX-2 expression is increased in the cytoplasm of bladder cells, during loss of cell differentiation (rs = 0.61, P-value < .001) and in muscle invasive carcinomas (P-value < .001). A strong positive association between tumor grade and nuclear expression of NFκB has been established. A positive correlation between COX-2 and nuclear NFκB immunoreactivity was observed. Conclusions. The possible coordinated upregulation of NFκB and COX-2, during bladder carcinogenesis, indicates that agents inhibitors of these two molecules may represent a possible new treatment strategy, by virtue of their role in bladder carcinogenesis

Cerebropulmonary dysgenetic syndrome

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Experimental and Molecular Pathology 85 (2008): 112-116, doi:10.1016/j.yexmp.2008.04.006.Ventilatory treatment of neonatal respiratory distress often results in bronchopulmonary dysplasia from congenital surfactant deficiency due to mutants of transporter protein ABCA3. Association of this condition with other severe disorders in premature newborns has not heretofore been reported. A neonatal autopsy included an in vivo whole blood sample for genetic tcsting. Autopsy revealed severe interstitial pulmonary fibrosis at age 8 days with heterozygotic mutation p.E292V of ABCA3 and severe dystrophic retardation of cerebral cortcx and cerebellum. Subsequently, 1300 archival neonatal autopsies, 1983-2006, were reviewed for comparable concurrent findings and bronchopulmonary dysplasia or retarded cerebral dystrophy lacking the other principal feature of this syndrome. Archival review revealed four similar cases and eight less so, without gene analysis. Further review for bronchopulmonary dysplasia revealed 59 cases, 1983-2006. Several other examples of similar retarded migration of germinal matrix and underdevelopment of cortical mantle, without pulmonary lesions of this type, were identified. The determination of an ABCA3 mutation in one case of severe pulmonary fibrosis with significant dystrophy of the brain and the identification of four highly similar archival cases and eight others with partial pathological findings supports the designation of an independent disorder, here referred to as the cerebroprrlmonary dysgenetic syndrome

Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional, and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the re-epithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-II pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development