Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are few cytogenetic studies of early (non-invasive) bladder cancer, particularly in situ carcinoma, due to technical difficulties in examining such lesions. The best approach is to extrapolate from chromosomal changes in more advanced cancers. Although no specific chromosomal changes have been established in either early or fully developed bladder cancers, certain recurrent anomalies have been encountered. Anomalies such as +1, +7, -9, 5q- or i(5p), 11p- and -Y appear to constitute part of the multistep carcinogenetic process by which clinically and pathologically recognizable bladder cancers develop. Since loss of part or all of chromosome 9 (-9) is a common and early cytogenetic event in bladder cancer, the detection of -9 in bladder washings or urine by fluorescence in situ hybridization (FISH) may be a promising test for early or recurrent bladder cancer. Although less frequent than -9, trisomy 7 (+7) is common enough to serve a similar purpose. In contrast, loss of the Y chromosome may indicate an advanced stage of bladder cancer. Thus, FISH studies utilizing probes for chromosomes 7, 9, and Y should yield cogent information to identify early bladder cancer. Cytogenetic (including FISH) studies combined with certain molecular approaches (e.g., p53 mutations detected immunochemically) may not only serve to differentiate early cancer from benign tumors or conditions, but may also help establish cancer stage. This would supply data of considerable usefulness to the clinician and pathologist.
 ...
PMID:Chromosome changes in early bladder neoplasms. 130 93

Transitional-cell carcinoma of the bladder is believed to arise through a series of genetic changes affecting cell growth and proliferation. Two basic types of such genes have been described: protooncogenes and tumor suppressor genes. The former have not been studied extensively in bladder cancer, although there is evidence that c-erb B-2/neu is overexpressed. Loss of specific chromosomal regions, which is common in bladder tumors, may inactivate tumor suppressor genes, of which p53 has received the most attention. Work also has been done on epidermal growth factor and its receptor, yielding evidence that malignant and normal urothelium have different sensitivities to its action. Although several advances must be made before genetic changes come to the clinical forefront, the information now being gained with such speed holds considerable promise for diagnosis and treatment.
 ...
PMID:Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes, and growth factors. 144 Oct 21

In the search for sensitive and specific tumor markers for bladder carcinoma, expression of various oncogenes and gene products (such as c-erb B-2, p53) and epidermal growth factor receptor merits particular attention. Although the results are not yet conclusive, important predictive markers are about to emerge from ongoing studies in this field. Bacillus Calmette-Guerrin treatment in superficial bladder cancer is probably the most successful immunotherapy in humans. But there is still a large knowledge deficit in the issues of optimal dose schedule and mechanisms of action. Although promising results of neoadjuvant chemotherapy in patients with invasive bladder cancers are reported, we must be cautious about changing our conventional approach until the results of large scale, controlled, randomized studies evaluating the survival are published.
 ...
PMID:Bladder cancer. 149 53

Structural alterations of the p53 gene were investigated to elucidate the molecular biological difference between superficial and invasive bladder cancer by polymerase chain reaction single-strand conformation polymorphism analysis. In 25 bladder cancers obtained from 23 patients, p53 gene mutations were investigated in exon regions 4 to 11. Twenty-four were transitional cell carcinomas, and the remaining one was a squamous cell carcinoma. Only one of 13 superficial bladder cancers, including pTis, pTa, and pT1, was found to have p53 gene mutation. However, of 12 invasive bladder cancers with pT2, pT3, and pT4, six primary carcinomas, including a squamous cell carcinoma and one metastatic carcinoma, were found to have p53 gene mutations. The number of cancers examined in Grades 1, 2, and 3 was three, seven, and 15, respectively. p53 gene mutation was not found in any of the ten cancers with Grades 1 and 2, while eight of 15 bladder cancers with Grade 3 were found to have p53 gene mutation. The results indicated that the incidence of p53 gene mutations appeared to be much higher in invasive-type and high-grade bladder cancers than in superficial and low-grade ones. Our results are compatible with the recently published results by Sidransky et al. [Science (Washington DC), 252: 706-709, 1991] showing that p53 gene mutations were frequently found in invasive bladder cancers by sequence analysis on polymerase chain reaction amplified products corresponding to exons 5 to 9. Our results are also compatible with previously reported results by Olumi et al. (Cancer Res., 50: 7081-7083, 1990) showing that the loss of chromosome 17p, revealed by analysis with restriction fragment length polymorphism, was frequent in high-grade bladder cancers. In this study, p53 gene mutations were often found in exon 4 as well as in other exons. Therefore, this region should also be examined for screening of mutations of this gene in bladder cancer. There appeared to be no consistent mutation sites in exons 4 to 11 of the p53 gene and no specific patterns of the mutation in bladder cancer.
 ...
PMID:Frequent association of p53 gene mutation in invasive bladder cancer. 154 Sep 47

Recent studies have provided the first clues as to the molecular mechanisms responsible for bladder carcinogenesis. Cytogenetic and molecular studies have demonstrated nonrandom changes of chromosomes 1, 5, 7, 9, 11, and 17. The finding of monosomy of chromosome 9 in early noninvasive lesions has initiated a search for a bladder-specific gene responsible for bladder oncogenesis. Activation of ras and erbB oncogenes has been reported, although the role that these changes play in bladder cancer is not yet understood. Inactivation of two well-characterized tumor suppressor genes, p53 and Rb, also appears to be important in the pathogenesis of bladder cancer, and evidence suggests that inactivation of p53 correlates with the acquisition by bladder cancer cells of the invasive phenotype. Although the picture is far from complete, it is clear that for the first time an understanding of the molecular events responsible for bladder cancer is possible, and that this information will have clinical impact on patients in the near future.
 ...
PMID:Molecular biology of bladder cancer. 155 51

Cigarette smoking and certain types of occupational exposure to arylamines appear to be the main cause of human urinary bladder cancer. Little is known of the promotion of bladder cancer in humans, although this stage has been demonstrated in rodents. Perhaps as a consequence of initiation, multifactorial alterations of cellular genes occur. These genes include the epidermal growth factor receptor gene, erbB-2, int-2, hst, and H-ras, which exert positive control over cell growth, as well as the suppressor genes Rb-1, and the gene coding for p53. Chromosomal changes such as deletions, translocations and/or amplifications related to these genes may be of significance for prognosis of this disease.
 ...
PMID:Chemical carcinogenesis of the urinary bladder--a status report. 161 88

The human p53 gene, a putative tumor suppressor gene, has a polymorphism in amino acid residue 72. We recently developed a method of detecting codon 72 polymorphism in this gene by digestion of polymerase chain reaction-amplified DNA using an allele-specific restriction endonuclease. This polymorphism allows the identification of loss of heterozygosity for the coding region of the p53 gene in limited tissue samples in a short time without using radioactive materials. We examined 33 patients with renal cell carcinoma and 29 with bladder cancer; heterozygosity in the p53 gene was lost in 60% (6 of 10 cases) and 73% (8 of 11 cases) of the renal and bladder tumors, respectively. Additionally, the assay's sensitivity could be improved by using DNA extracted from frozen sections of the tumors. Because the proportions of tumor cells and nontumor cells could be assessed by microscopic evaluation of the frozen sections, we were able to minimize contamination from nontumor cells, which occasionally causes false readings of retained heterozygosity. This simple and sensitive method for detecting loss of heterozygosity in the p53 gene makes it possible to rapidly screen a large number of tissue samples and has the potential to be a useful diagnostic tool for a wide variety of human neoplasms.
 ...
PMID:Detection of loss of heterozygosity in the p53 gene in renal cell carcinoma and bladder cancer using the polymerase chain reaction. 200 30

Overexpression of p53 and erbB-2 was studied by immunohistochemistry in formalin-fixed tissue samples of 179 patients with transitional cell carcinoma of the urinary bladder. p53 immunostaining was strongly correlated with tumour stage (P < 0.0001). This was driven by a marked difference in p53 expression between pTa (37% positive) and pT1 (71%) tumours, while there was no difference between pT1 and pT2-4 tumours. Similarly, a strong overall association between p53 expression and grade (P < 0.0001) was driven by a marked difference between grade 1 (28%) and grade 2 tumours (71%), and there was no significant difference between grade 2 and grade 3 tumours. Surprisingly, the frequency of erbB-2 overexpression was higher in pT1 tumours (74%) than in either pTa (49%; P = 0.0265) or pT2-T4 (56%; P = 0.0645) tumours. Both p53 and erbB-2 expression was also associated with metastasis. Metastases were found in 77% of patients with p53 positive primary tumours, but in only 50% of the patients with p53 negative primary tumours (P = 0.022). Metastases were found in 66% of patients with erbB-2 positive primaries, but in only 37% of the erbB-2 negative primaries (P = 0.020). Of 32 patients with positivity for both p53 and erbB-2, 84% developed metastases, as compared to 49% of patients with positivity for either one or neither positive (P = 0.002). We conclude that both p53 and erbB-2 overexpression are associated with early invasion in bladder cancer. Furthermore, p53 and erbB-2 may be important predictors for metastasis.
 ...
PMID:p53 and erbB-2 protein overexpression are associated with early invasion and metastasis in bladder cancer. 750 41

p53 gene function and tumor cell proliferation are thought to be important parameters for tumor progression in bladder cancer. In this study immunohistochemistry and fluorescence in situ hybridization were used to determine the relationship between p53 alterations, tumor proliferation (Ki-67 Labeling Index), and numerical chromosomal aberrations in formalin fixed bladder tumors. p53 expression was associated with Ki-67 LI (p = 0.0014), polysomy 17 (p = 0.001) and polysomy 7 (p = 0.0241). This is further evidence for a significant role of the p53 gene in proliferation control and preservation of genomic stability.
 ...
PMID:[Ki-67 fraction, p53 alteration and numerical chromosome aberrations (chromosomes 7 and 17) in formalin fixed bladder tumors]. 751 Dec 86

We used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in approximately 1600 revertants of Salmonella induced by cigarette smoke condensate (CSC) in the presence of S9. CSC induced approximately 80% GC-->TA transversions and approximately 20% GC-->AT transitions at the base-substitution allele (hisG46) in strain TA100. This spectrum was similar to those of the polycyclic aromatic hydrocarbon (PAH) benzo[alpha]pyrene and various aromatic amines such as 4-aminobiphenyl and Glu-P-1, all of which are present in CSC. This spectrum was also similar to that produced by PAHs in other bacteria, mammalian cells, and rodents as well as to that of the p53 gene in lung tumors from smokers. The results in Salmonella are consistent with a role for the PAH component of cigarette smoke in the base-substitution specificity found in the p53 gene of smoking-associated lung tumors. At the frameshift allele in strains TA1538 and TA98, CSC induced only a hotspot 2-base deletion, which is a mutation spectrum that is identical to that induced by the heterocyclic amine pyrolysate products of amino acids, such as Glu-P-1. This is consistent with bioassay-directed fractionation studies showing that aromatic amines account for most of the frameshift specificity of CSC in Salmonella. Rodent and human studies indicate that aromatic amines are responsible for smoking-associated bladder cancer. Repeated freezing and thawing of the CSC samples changed the chemical composition of the mixtures as evidenced by the production of an altered mutation spectrum. This emphasizes the necessity of proper storage and handling of labile complex mixtures. This study (i) confirms our previous studies showing that the mutation spectrum of a complex mixture reflects the dominance of one or a few classes of chemical mutagens within the mixture, and (ii) illustrates the potential of bioassay-directed molecular analysis for identifying the chemical classes in a complex mixture that are responsible for specific classes of mutation and tumor types produced by the mixture.
 ...
PMID:Mutation spectrum of cigarette smoke condensate in Salmonella: comparison to mutations in smoking-associated tumors. 758 63


1 2 3 4 5 6 7 8 9 10 Next >>