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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of radiotherapy for the treatment of clinical stage T3b transitional cell carcinoma of the bladder is controversial. The options range from definitive radiotherapy alone, to preoperative radiotherapy and cystectomy, to chemotherapy and radiation for bladder preservation. Our data show that long-term local control after definitive radiotherapy is only 27% and that death attributable to local-regional failure in this setting is 43%. Thus, definitive radiotherapy is only used in patients who are considered poor candidates for surgical and chemotherapy procedures. Preoperative radiotherapy (PREOP) has been studied in a number of randomized series, all of which failed to establish an improvement in patient outcome over those treated with radical cystectomy alone (CYST). However, these studies are subject to criticism, mostly because of poor patient accrual and low numbers of patients available for the analyses. A retrospective review of patients treated at MD Anderson Cancer Center indicates that local control is superior with PREOP as compared with CYST. An analysis of the impact of local control on distant metastasis rates in patients treated with CYST showed that local control was an independent correlate of distant metastasis and survival. Thus, preoperative radiotherapy may be beneficial to patients with late-stage muscle-invasive bladder cancer by securing local control and reducing distant metastasis rates as a result. The success of bladder preservation for stage T3b patients rests with the ability to select patients with radiosensitive tumors. To this end, the immunohistochemical staining status of tumor p53 and pRB was investigated in patients treated with PREOP. Abnormal pRB expression was very strongly related to radiation response, whereas altered p53 expression was associated with high distant metastasis-free and overall survival rates. These two molecular markers were complementary and show promise in facilitating the selection of late-stage patients for bladder preservation.
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PMID:Radiotherapy for stage T3b transitional cell carcinoma of the bladder. 873 36

To evaluate the significance of p53 overexpression on the progression of bladder cancer, seven patients with Ta bladder cancer who eventually progressed to the invasive stage ( > or = stage T1) were immunohistochemically analyzed. The immunohistochemical study was performed using the p53 protein antibody on formalin-fixed, paraffin-embedded tissue sections from all primary and recurrent tumors. In three patients, immunoreactivity was detected only at the time of disease progression, suggesting that p53 mutation may be related to the disease. However, since no staining could not be found in stage Ta bladder cancer, the patient with a risk of progression could not be detected by this immunohistochemical study.
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PMID:[Immunohistochemical examination for p53 overexpression in Ta bladder cancer with disease progression]. 875 36

In this study, we found an unexpected association (crude odds ratio = 2.8; 95% confidence interval = 0.9-8.4) between definite work-related exposure to asbestos and carcinoma of the urinary bladder in a small group of patients (n = 28) initially recruited as referents for an epidemiological feasibility study on the occupational causes of lung cancer. We extended the study by using molecular methods to examine mutations in the p53 tumor suppressor gene in the same cases of bladder cancers. The same number of archival samples of transitional cell carcinoma, mainly of grade 3, were added to the analysis. We failed to show any association between occupational exposure to asbestos and p53 mutations among bladder cancer patients. We observed an increasing occurrence of p53 mutations in nonsmokers (5 of 17, 29%), former smokers (8 of 21, 38%), and current smokers (9 of 16, 56%) in that order; however, this was not statistically significant. The most prevalent type of mutation was G:C to A:T transition. Tumor grade was not associated with the frequency of mutations, but the higher stage (T3-T4) tumors appeared to have mutations more frequently than did the less invasive tumors (T1-T2).
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PMID:A molecular and epidemiological study on bladder cancer: p53 mutations, tobacco smoking, and occupational exposure to asbestos. 877 Apr 64

We report here a compilation of p53 mutation results from two smoking-related cancers, lung cancer and bladder cancer. The overall mutation frequencies reported for these two types of cancer were relatively similar--50% in lung cancer and 40% in bladder cancer. The compiled data from lung cancer and bladder cancer suggest an increasing proportion of patients with p53 mutations in nonsmokers, former smokers, and current smokers, in that order, in both cancer groups. Taken together, more than half (55% and 56% for lung cancer and bladder cancer, respectively) of the patients who continued smoking (CS), less than 40% (38% and 38%) of those who had stopped smoking before > or = 1 or > or = 5 years) clinical diagnosis (ES), and less than 30% (25% and 29%) of those who were nonsmokers (NS) had a p53 mutation. The differences seen in the mutation frequencies between the three smoking groups did not, however, reach statistical significance (lung cancer--CS vs ES: odds ratio [OR] = 2.0, 95% CI 0.7-5.4; CS vs NS: OR = 3.7, 95% CI 0.4-37; bladder cancer--CS vs ES: OR = 2.1, 95% CI 0.6-7.9; CS vs NS: OR = 3.1, 95% CI 0.7-13). Guanine to thymine transversions were the most common type in lung cancer followed by guanine to adenine transitions. In bladder cancer, on the contrary, G:C to A:T transitions at cytosine-guanine dinucleotide sites were the most frequently detected base substitutions. Analysis of the compiled p53 mutation data suggest that, in addition to lifetime cumulative exposure to cigarette smoke, also stopping smoking for years prior to clinical manifestation of the disease may affect the incidence of p53 mutations. The differences in the mutation profiles appear to support the view that the main genotoxic agents from cigarette smoke exposure may be different in bladder cancer as compared to lung cancer, as suggested previously by DNA adduct studies.
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PMID:Cigarette smoking and p53 mutations in lung cancer and bladder cancer. 878 82

Recent molecular biology investigations have demonstrated that tumor progression and dissemination in bladder cancer is a highly complicated phenomenon, consisting of multiple distinct steps and regulated by a great number of different genes. Some of these genes involved in the specific steps of tumor progression and dissemination have been identified. Several oncogenes, e.g., the epithelial growth factor receptor (EGF-R), and tumor-suppressor genes, e.g., the p53 gene, have been found to correlate significantly with tumor progression. The decreased expression of cell-adhesion molecules such as E-cadherin appears to facilitate tumor-cell detachment in the primary tumor, whereas expression of the intercellular adhesion molecule (ICAM)-1 might be of relevance for cell attachment at the metastatic site. Tumor invasion through the basement membrane has been correlated with a decreased expression of laminin and elevated urinary levels of acidic fibroblast growth factor. Although the complex processes related to dissemination are far from being completely understood, the finding of differential expression of distinct genes appears to provide the first targets for therapeutic intervention.
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PMID:Molecular biology of dissemination in bladder cancer--laboratory findings and clinical significance. 880 98

Cell growth arrest is a common response to DNA damage by ionising irradiation and the p53 gene has been shown to play an important role in this mechanism, possibly in a tissue-specific manner. Mutations in the p53 gene are frequent in invasive bladder cancers, which are often treated by radiotherapy. In this paper we have investigated the growth response to X-irradiation of three bladder cancer cell lines with differing p53 status: UCRU-BL-17 overexpresses mutant p53, while UCRU-BL-13 and UCRU-BL-28 contain wt P53. We have also examined the expression of proteins reported to be part of the p53 control pathway in response to irradiation-induced DNA damage. No G1 arrest was detectable in any of the cell lines after ionising irradiation; furthermore, in a downstream event reported to be correlated with p53 function there was no increase in WAF-1 protein levels regardless of p53 status. Rather, ionising irradiation resulted in G2 arrest, but the extent of this was not related to p53 status. p16 levels were also not affected by irradiation. Our results suggest that the UCRU-BL-28 cell line may have a defect in the p53-cell control pathway upstream of p53, while UCRU-BL-13 cells may have a defect downstream between p53 and WAF-1.
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PMID:Studies of X-irradiated bladder cancer cell lines showing differences in p53 status: absence of a p53-dependent cell cycle checkpoint pathway. 880 1

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric-gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.
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PMID:APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis. 880 79

This study is aimed at determining the usefulness of nuclear DNA content and S-phase fraction (SPF) to predict tumor recurrence in papillary superficial bladder cancer. Tumor DNA content and SPF were measured by flow cytometry on formalin-fixed, paraffin-embedded tissue from 199 newly diagnosed pTa/pT1 transitional cell carcinomas of patients enrolled into a multicenter prospective study from 1990 to 1992. The follow-up extended up to March 1994, and, at last follow-up, 122 (61.3%) patients have experienced at least one recurrence. After exclusion of 34 cases, whose coefficient of variation exceeded 8%, 131 (79.4%) tumors were diploid, and 34 (20.6%) were aneuploid. There was no association between tumor DNA content and time to first recurrence. Diploid tumors with low SPF (< 11%) tended to have a longer recurrence-free survival (RFS) than those with high SPF, but this difference did not reach statistical significance (P = .2833). SPF in aneuploid tumors did not add any new information. Aneuploidy was associated with higher stage (P < .001), poorer grade (P < .002), multifocality (P = .028), Her-2/neu (P = .021), and p53 (P = .033) expression. High SPF correlated with higher stage (P = .066) and higher grade (P = .025). This study shows that DNA-ploidy and SPF measured on a single superficial bladder cancer specimen are not predictive of tumor recurrence. The frequent multifocality of the disease may explain, in part, these findings.
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PMID:Prognostic significance of nuclear DNA content and S-phase fraction by flow cytometry in primary papillary superficial bladder cancer. 881 87

Recent investigations have demonstrated p53 and Rb alterations in a subset of transitional cell carcinoma (TCC). Further genetic changes during tumor progression include overexpression of the c-myc gene in a significant number of mainly invasive bladder tumors. To study the possible interactions between these genes in TCC, urothelial cancer cell lines were chosen as an in vitro model. Expression and mutation of p53 was studied in 15 bladder cancer cell lines by immunocytochemistry, Western blot, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing of double stranded PCR products of exons 4, 5, 7 and 8 of genomic DNA. C-myc expression and gene structure were studied using Northern and Southern blot techniques Rb protein expression was analyzed by Western blot. Twelve of 15 cell lines showed either p53 mutations or abnormal protein expression. Consistent with previous studies, five cell lines did not express Rb protein. None of the cell lines studied retained both tumor suppressor genes in a functional form. The c-myc gene appeared to be intact in all cell lines and copy numbers were close to normal. Northern analysis demonstrated that all cell lines expressed c-myc mRNA but evidence for altered regulation was found in at least two cell lines. Our data suggest that amplification or translocation are not the underlying mechanism for c-myc overexpression in urothelial tumors. No correlation between loss of Rb protein and c-myc expression was observed. The results presented here for the cell lines match well those obtained in vivo. Thus, these cell lines may provide a suitable model for further analysis of molecular alterations in urothelial cancer.
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PMID:Inactivation of tumor suppressor genes and deregulation of the c-myc gene in urothelial cancer cell lines. 883 85

Retroviral vectors were used to introduce the wild-type p53 gene into human bladder cancer cell lines BIU-87 and EJ, which express endogenous wt-p53 gene and have a mutation in H-ras gene. The expression of the exogenous wt-p53 gene in cells suppresses the growth of the bladder cancer cells in standard culture and in soft agar and blocks the cell cycle progression in G1. The BIU-87 and EJ cells developed tumors with average volumes of 6.53 cm3 and 6.61 cm3 in nude mice in 9 weeks after inoculation, while the cells transduced with wt-p53 gene failed to form tumors. The expression of H-ras gene in bladder cancer cells was reduced at mRNA level. These results suggest that the overexpression of the wt-p53 gene suppresses the expression of mutant H-ras gene and inhibits the tumor cell growth in vivo and in vitro.
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PMID:Introduction of wild-type p53 gene downregulates the expression of H-ras gene and suppresses the growth of bladder cancer cells. 883 87


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