Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biphenyl and its derivatives, 2-aminobiphenyl, 2-nitrobiphenyl, 4-aminobiphenyl, 4-nitrobiphenyl, p-phenylphenol, o-phenylphenol (OPP), and o-phenylphenol sodium salt tetrahydrate (OPP-Na) were examined for their bladder carcinogenicity in rats by a short-term assay for agglutinability of bladder epithelial cells with concanavalin A. Increased agglutinability was observed after 1-week treatment with 2.0% and 1.0% OPP, 2.0% and 1.0% OPP-Na, 0.5 and 0.1% 4-aminobiphenyl, and 0.5% 4-nitrobiphenyl in the diet, suggesting carcinogenicity of these compounds in the bladder. Such an increase in agglutinability was not observed in rats fed diets containing biphenyl, 2-aminobiphenyl, 2-nitrobiphenyl or p-phenylphenol at 2.0%. With OPP-Na, an in vivo carcinogenesis experiment was performed. Bladder carcinomas developed in 14 of 36 male Fisher rats fed a 2% OPP-Na diet for 50 weeks.
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PMID:Increased agglutinability of bladder epithelial cells by concanavalin A in rats fed several biphenyl derivatives. 665 51

The present investigation was conducted to determine a single dose of the carcinogen N-methyl-N-nitrosourea (MNU) which remains subcarcinogenic in a heterotopically transplanted rat urinary bladder with a communicating reservoir (HTB) either in a urine-free or urine-existing environment. A single dose of MNU, either 0.1 mg or 0.025 mg, was instilled directly into the HTB, and was followed by weekly instillation of normal rat urine or 2.1% NaCl solution (equiosmolar to the urine) for up to 52 weeks. Bladder tumors observed were divided into 2 categories depending upon their location. Those arising at the hyperplastic foci which were induced by mechanical irritation by the connector tip were referred to as inflammatory polyp (IP)-related tumors and those arising in the region free from the IP changes were referred to as IP-unrelated tumors. The results indicated that both carcinogen levels fail to induce IP-related or IP-unrelated tumors in the urine-free environment. In the presence of urine, however, the high MNU dose (0.1 mg) was tumorigenic at both IP-related and IP-unrelated sites, whereas, the low MNU dose exhibited tumorigenicity only at the IP-related site. Physical irritation by the connector enhanced MNU-initiated tumorigenesis at the connector tip only in the presence of urine in bladder lumen. Physical irritation per se induced tumors at the connector tip even without prior carcinogen treatment provided urine was present in the HTBs.
Carcinogenesis 1983
PMID:A minimal dose of N-methyl-N-nitrosourea carcinogenic to heterotopically transplanted rat urinary bladder. 685 Sep 85

Aromatic amines, including 2-naphthylamine, 4-aminobiphenyl and benzidine, are known urinary bladder carcinogens in man and other species, but in rodents, aromatic amines and amides have usually induced liver tumors, occasionally also with tumors of the bladder and other tissues. Variations in organ specificity are related to differences in metabolism; for the production of bladder tumors, the rates of acetylation and deacetylation appear to be critical. Bladder specific carcinogens in rodents and other species have subsequently been identified, including N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) administered in the drinking water, N-[(4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) in the diet and N-methyl-N-nitrosourea (MNU) instilled intravesically. When low doses of several bladder carcinogens (BBN, FANFT, 2-acetylaminofluorene, and 3,3'-dichlorobenzidine) are administered to rats, either simultaneously or sequentially, a synergistic effect is observed with respect to bladder carcinogenesis. In addition, a multistage carcinogenesis process has been demonstrated for the rat bladder using MNU or FANFT as initiators, and dietary sodium saccharin, sodium cyclamate, or tryptophan as promoters. Calculi (or pellets) appear to enhance the promotion process but are not necessary for it to occur. Recent studies also indicate that urine has a role in the promoting process. The urothelium normally has a very low mitotic rate. If mucosal proliferation is increased, such as during fetal development or during regeneration and repair of an ulcer, the bladder appears to be considerably more sensitive to the effects of promoting substances. For example, if sodium saccharin is administered to rats after ulceration of the bladder, even without prior administration of an initiator, bladder carcinoma develops. Under these conditions, the substance appears as a carcinogen. Human populations with increased bladder epithelial proliferation, such as fetus, infants, patients with bacterial cystitis or men with partially obstructive prostatism, may have increased susceptibility to the action of carcinogenic or promoting stimuli.
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PMID:Promotion in urinary bladder carcinogenesis. 687 31

This article reviews the association between bilharziasis and bladder cancer. Cancer of the bladder is a well documented sequelae of chronic infection with Schistosoma haematobium. Bilharzial bladder cancer is a major cause of morbidity in many countries; it remains the most commonly diagnosed cancer of Egyptian men. Bilharzial tumors may be differentiated from non-bilharzial tumors by their younger age of onset, greater male/female ratio, pathology and clinical presentation. Bladder tumors have been successfully induced in animals exposed to S. haematobium cercariae. Dietary nitrosamines may exacerbate the induction of bladder cancer in the presence of S. haematobium. The exact mechanism of bilharzial bladder carcinogenesis remains unknown.
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PMID:Helminths in the induction of cancer II. Schistosoma haematobium and bladder cancer. 701 36

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.
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PMID:Two molecular pathways to transitional cell carcinoma of the bladder. 830 42

Bladder augmentation with segments of the gastrointestinal tract is commonly used to treat patients with small or noncompliant bladders. Reliable data on the incidence of tumors in patients with enterocystoplasty are not available. In the small number of cases reported in the literature the mean latency period is approximately 18 years. We designed a study in Sprague Dawley rats to try to determine the risk of carcinogenesis in different types of augmentation cystoplasty and its possible relationship with infected urine, and to investigate the possibility of detecting the tumors by cytological analysis. We performed 30 gastrocystoplasties, 35 sigmoid cystoplasties, 30 ileocystoplasties and 10 sham operations, and used 10 nonoperated animals as controls. The animals were sacrificed upon completing 1 year of followup and bladder urine samples were collected at the time of sacrifice. Of 115 animals 86 were available for histological evaluation (26 gastrocystoplasty, 22 sigmoid cystoplasty, 18 ileocystoplasty, and all sham and control animals). Mean followup was 11.2 months in the gastrocystoplasty, 11.8 months in the sigmoid cystoplasty, and 12 months in the ileocystoplasty, sham and control groups. Multifocal or superficial transitional metaplasia was found in 65.4% of the gastrocystoplasty, 50% of the sigmoid cystoplasty and 55.5% of the ileocystoplasty animals. Proliferations that we classified as papillary hyperplasia were present in 53.8% of the gastrocystoplasty, 40.9% of the sigmoid cystoplasty and none of the ileocystoplasty rats. The proliferations occurred either at or close to the anastomosis between the bladder and the gastric or colonic patch, or in areas of transitional metaplasia. Cytological urinalysis was negative for neoplastic cells in all cases. No correlation was found between the occurrence of papillary hyperplasia and urinary infection. These data indicate that in rats transitional metaplasia is common in gastrocystoplasty, sigmoid cystoplasty and ileocystoplasty, and that papillary hyperplasia may occur near or at the anastomosis, or in areas of transitional metaplasia in either gastrocytoplasty or sigmoid cystoplasty. In contrast to other studies, we observed no examples of papillary hyperplasia in the ileocystoplasty group in this series. No transitional cell carcinomas or adenocarcinomas were identified in this study. It is not known if these papillary lesions have an increased malignant potential, thus further studies with longer followup are warranted.
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PMID:The development of tumors in experimental gastroenterocystoplasty. 832 35

We examined the effect of acetylsalicylic acid (ASA) on n-butyl-(4-hydroxybutyl)nitrosamine (BHBN)-induced bladder carcinogenesis in male Wistar rats. Of 29 rats that received 0.05% BHBN in their drinking water for 9 weeks, 8 developed bladder cancer. Only 1 out of 29 rats that received 0.1% ASA in their diet for 20 weeks, including the period of BHBN consumption, developed a tumor. That difference is statistically significant. Bladder weight was significantly higher in rats given BHBN than in controls and in rats given both BHBN and ASA. We conclude that ASA inhibits BHBN-induced bladder carcinogenesis.
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PMID:Acetylsalicylic acid inhibition of n-butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats. 850 38

Bladder cancers display different forms from superficial to aggressive tumours with muscle invasion. Many studies on this disease have been carried out in order to better understand the molecular mechanisms involved in its progression. Two loci are frequently associated with bladder tumorigenesis. The chromosome 9 lesions seem to be earlier involved in carcinogenesis, and suggest the presence of a tumour suppressor gene, and on the other hand the TP53 gene mutations (17q13.1) are later but take place in tumour progression. These alterations could be used as early diagnosis tool in bladder tumours and orientate the search for the bladder cancer gatekeeper gene(s).
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PMID:[Tracking the gatekeeper gene in the stages of carcinogenesis in the bladder]. 943 99

We have previously shown that bladder urothelium of people living in the cesium-137 ((137)Cs)-contaminated areas of Ukraine demonstrates accumulation of stable p53 and p53 mutational inactivation, preferentially through G:C to A:T transition mutations at CpG dinucleotides, with a codon 245 hot spot. In the present study, we analyzed immuno-histochemically the relationship between oxidative stress markers and over-expression of p53 and H-ras in urinary bladder urothelium from 42 men with benign prostatic hyperplasia. Bladder mapping biopsies were obtained from 15 patients from a highly radiocontaminated area (group I), 14 patients from the less contaminated city of Kiev (group II) and 13 patients as a control group from "clean" (without radiocontamination) areas of Ukraine (group III). Irradiation cystitis with multiple foci of severe dysplasia and carcinoma in situ were observed in 15 of 15 (100%, group I) and 9 of 14 (64%, group II) cases, with 4 small transitional-cell carcinomas incidentally detected in groups I and II. Markedly elevated levels of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and 8-hydroxy-2;-deoxyguanosine (8-OHdG) were noted in these bladder urothelial lesions from groups I and II, accompanied by strong over-expression of p53 and less H-ras expression. These findings support the hypothesis that iNOS, COX-2 and 8-OHdG in bladder urothelium are induced by long-term exposure to low-dose radiation with a close relationship to p53 over-expression that could predispose to bladder carcinogenesis.
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PMID:Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident. 1084 92

This study was designed to investigate the role of the epidermal growth factor receptor (EGFR) and its ligands in chemically induced mouse bladder cancer. Bladder tumours were induced in C57Bl/6 and B6D2F1 mice by treatment with the carcinogen, N:-butyl-N:-(4-hydroxybutyl) nitrosamine (BBN). The levels of mRNA for EGFR and its ligands were analysed by reverse transcription-polymerase chain reaction (RT-PCR) in bladder tumours and in normal bladder urothelia. EGFR mRNA was detected in all tumours, transforming growth factor alpha (TGFalpha) mRNA levels were similar to those in normal bladder urothelia or were decreased and mRNA levels for amphiregulin, heparin-binding epidermal growth factor-like factor (HB-EGF) and betacellulin were significantly higher than those in normal urothelia. Seven cell lines were derived from chemically induced tumours. These cell lines were able to grow in serum-free conditions. All the cell lines tested expressed the genes encoding EGFR and at least one of its ligands. Proliferation of these cell lines was inhibited by AG1478, a specific EGFR tyrosine kinase inhibitor, strongly suggesting that EGFR was involved in cell growth. As expected, EGFR was found to be phosphorylated in serum-free medium, this phosphorylation being inhibited by AG1478. Conditioned medium of a bladder cancer cell line had EGFR-stimulating activity and an antibody directed against EGFR inhibited proliferation by 45%. This suggests that tumour cell growth is stimulated by an autocrine loop involving EGFR and secreted growth factors. AG1478 decreased the expression of genes for amphiregulin, HB-EGF and betacellulin, showing that EGFR activation induces up-regulation of the EGFR ligands. These results suggest that EGFR plays a critical role in bladder tumour progression.
Carcinogenesis 2000 Dec
PMID:Involvement of epidermal growth factor receptor in chemically induced mouse bladder tumour progression. 1113 10


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