Tumorigenesis Of Bladder Cancer Research Articles

Bladder cancer in Africa: Update

Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation. Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative.

Immunohistochemical analysis of expression and allelotype of mismatch repair genes (hMLH1 and hMSH2) in bladder cancer.

Mutation of human homologues of DNA mismatch repair (MMR) genes in tumours has been shown to be associated with the phenomenon of microsatellite instability (MSI). Several studies have reported the occurrence of MSI in bladder cancer, but evidence of involvement of MMR genes in the pathogenesis of this cancer is still unclear. We therefore utilized quantitative immunohistochemical (IHC) image analysis and PCR-based allelotype analysis to determine hMLH1 and hMSH2 genes alteration in a cohort of Egyptian bladder cancer samples. IHC analysis of 24 TCC and 12 SCC revealed marked- intra and intertumour heterogeneity in the levels of expression of the two MMR proteins. One TCC lost MLH1 expression and one lost MSH2, (1/24, 4%), and one SCC lost MSH2 (1/12, 8%). A large proportion of analysed tumours revealed a percentage positivity of less than 50% for MLH1 and MSH2 expression (44% and 69%, respectively). Complete loss of heterozygosity in three dinucleotide repeats lying within, or in close proximity to, hMLH1 and hMSH2 was rare (2/57, (4%) for MLH1; and 1/55, (2%) for MSH2), however allelic imbalance was detected in 11/57 (hMLH1) and 10/55 (hMSH2) at any of the informative microsatellite loci. These alterations in structure and expression of DNA MMR genes suggest their possible involvement in the tumorigenesis and/or progression of bladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

Changes in the activities of mitochondrial enzymes in the progress of tumorigenesis of bladder cancer.

To investigate changes in the activities of mitochondrial enzymes in the progress of tumorigenesis of bladder cancer, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen was administered orally to male Sprague-Dawley rats for eight weeks. The urinary bladders were harvested periodically for the evaluation of tumorigenesis. The activities of NADH cytochrome c reductase (NCCR), succinate cytochrone c reductase (SCCR) and cytochrome c oxidase (CCO) were measured. The NCCR and SCCR activities elevated significantly by the exposure of BBN and decreased rapidly when BBN was withdrawn. However, the CCO activity increased and reached plateau at 18 weeks in spite of the discontinuance of BBN. The results indicated that the NCCR, SCCR and CCO activities were significantly elevated in the tumorigenesis. However, the CCO enzyme may be more related to the progress of tumorigenesis of bladder cancer.

ALTERATIONS OF MICROSATELLITE REPEATS IN BLADDER-CANCER

Investigation of the genomic instability of microsatellite repeats indicates a new mechanism for human carcinogenesis. This study was conducted to determine whether such alterations in microsatellite repeats are associated with the onset of bladder cancer. Thirty-two primary bladder cancer DNA samples were examined for genomic instability at (CA)n repeats on human chromosomes 5q (D5S107), 17p (D17S261) and 18q (DCC) by polymerase chain reaction (PCR) assay. Differences in unrelated microsatellites for tumor and normal DNA were detected in 6 of the 32 (18.8%) tumors examined. These six tumors were beyond grade 2 and stage pT2 invasive bladder tumors. However, only one of 32 (3.1%) showed alterations with more than 2 microsatellite probes. It follows that alterations of (CA)n microsatellite instability may be infrequent in the tumorigenesis of bladder cancer.