ABSTRACT
Tumors escape from immune surveillance by, among other mechanisms, the down- regulation of endothelial adhesion molecules, such as ICAM-1, and by unresponsiveness to inflammatory signals, a process mediated by angiogenic factors that is called endothelial cell anergy. Here we present the cell biological regulation of these processes. The angiogenic basic fibroblast growth factor (bFGF/FGF-2) was found to inhibit tumor necrosis factor-alpha (TNF-alpha)- induced elevation of ICAM-1, at transcriptional level. Furthermore, we found that bFGF inhibits the TNF-mediated activation of NF-kappaB by blocking phosphorylation and degradation of IkappaBalpha. We also found that bFGF induces hyperphosphorylation of p38 MAPK on endothelial cells, whereas inhibition of such kinase abrogates the effect of bFGF on the TNF-mediated activation of NF-kappaB. Thus, we suggest that bFGF acts as an inhibitor of leukocyte adhesion in tumor vessels by decreasing the ICAM-1 expression through the sustained activation of p38-MAPK and via inhibition of NF-kappaB.
Subject(s)
Clonal Anergy/physiology , Endothelium, Vascular/immunology , Fibroblast Growth Factor 2/physiology , NF-kappa B/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism , Cell Line , Down-Regulation/physiology , Endothelium, Vascular/enzymology , Endothelium, Vascular/metabolism , Enzyme Activation , Humans , Intercellular Adhesion Molecule-1/genetics , Phosphorylation , RNA, Messenger/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
C-myb structural alterations were analysed by Southern blot hybridization in 55 adenomatous polyps and 21 adenocarcinomas of the colon. Gene amplification was observed in 8 cases (14.5%) and c-myb rearrangements in 3 cases (5.4%) of the preneoplastic lesions analysed. A higher percentage of c-myb abnormalities (23.8%) was shown by malignant tumors. As far as mutant p53 protein is concerned, it was detected both in sera of adenoma and adenocarcinoma patients, though at different levels. No statistically significant correlations were found between c-myb or p53 abnormalities and clinico-pathological variables.
Subject(s)
Adenocarcinoma/genetics , Adenomatous Polyps/genetics , Colonic Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogenes , Tumor Suppressor Protein p53/blood , Adolescent , Adult , Aged , Aged, 80 and over , Female , Gene Amplification , Humans , Male , Middle Aged , Mutation , Proto-Oncogene Proteins c-mybABSTRACT
We investigated the presence of human papillomavirus-related DNA sequences (HPV 6, 11, 16 and 18) in 33 formalin-fixed paraffin-embedded biopsies from the urinary tract of female patients with recurrent and persistent urethritis and cystitis, using the polymerase chain reaction (PCR). The samples for PCR reaction were selected among tissues examined for histological diagnosis on the basis of the presence of microscopic changes consistent with HPV infection. Sequences homologous to HPV 6, 11 and 18 genome were not found, while HPV 16-related DNA sequences were identified in 25/33 lesions with histopathological diagnosis of metaplasia (1 from the urethra, 23 from the trigone and 1 from the bladder). The results suggest that the spread of HPV in the female urinary tract may not be uncommon and point to the need for further research on the possible pathogenic role in recurrent female disturbances.
