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

We attempted to isolate a carcinogenic substance from bracken fern (Pteridium aquilinum), a naturally occurring toxicant responsible for the production of chronic enzootic hematuria and urinary bladder cancer of cattle and carcinogenic for various target organs of several species. Hot methanol extracts of bracken fern were solubilized in water and extracted with chloroform followed by a mixture of n-butanol-butanone (1:1). That fraction was dried and triturated with ether-methanol (4:1), n-butanol, and finally absolute ethanol. The insoluble residue was dissolved in 10% aqueous methanol and passed through Dowex 1 OH-, Dowex 50 H+, or Dowex 1 OH- and then Dowex 50 H+ ion exchange resins. A condensed tannin, isolated from one ot the fractions, was identical to that isolated from bracken fern by the caffeine procedure used for the separation of tannins from other plant constituents. Three systems were used for bioassay; induction of bladder carcinoma by implantation of cholesterol pellets containing bracken fern fractions into the bladder lumens of mice; acute toxicity by ip injection of brachen fern fraction into mice; and growth inhibition of Escherichia coli. The following fractions induced significantly greater incidences of bladder carcinoma than did cholesterol pellets only: tannin, Dowex 50 H+, residue, n-butanol, and methanol. Tiliroside, a component of bracken fern fractions into the bladder lumens of mice; acute genic acid, and quercetin were not carcinogenic. Tannin was the most toxic (mean lethal dose: 0.16 mg/g) and carcinogenic. None of the carcinogenic fractions inhibited growth of E. coli.
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PMID:Identification of carcinogenic tannin isolated from Bracken fern (Pteridium aquilinum). 76

Epidemiological studies have suggested that genetically based polymorphism for N-acetylation of arylamines might play an important role in the susceptibility to bladder cancer induction. However, these studies show large differences in the extent of such susceptibility. We have undertaken collaborative investigations (with IARC, MIT, NCI and NCTR) which couple internal dosimetry among smokers (measurement of hemoglobin and DNA adducts of arylamines) with the assessment of metabolic polymorphism. In one of these studies, hemoglobin adducts of 14 arylamines (including 2-naphthylamine and 4-aminobiphenyl) were analysed in a group of 86 subjects (smokers and non-smokers) in order to establish whether the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. In another investigation on 100 smokers and non-smokers, metabolic polymorphism for N-acetylatransferase was assessed by measuring five different urinary metabolites of caffeine, after timed urine collection following coffee consumption. Arylamine-hemoglobin adducts were also measured. 4-Aminobiphenyl-hemoglobin adducts were found to be related to both the quantity and the type of tobacco smoked, as well as to the acetylator phenotype (independently of smoking habits).
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PMID:The use of biomarkers in epidemiology: the example of bladder cancer. 147 Nov 98

Our method to evaluate acetylator phenotype and N-oxidation phenotype with a single caffeine dose and a single urine specimen collection has enabled us to examine acetylation and N-oxidation by two enzyme systems that have a known genetic polymorphism and are important in aromatic amine metabolism. Based on available data, we have hypothesized patients with urinary bladder cancer will have a higher frequency of rapid N-oxidation and slow acetylation phenotypes when compared to controls. On the other hand, patients with colorectal cancer should contain a higher proportion of both rapid N-oxidation phenotype and rapid acetylation phenotype when compared to the control group. In contrast, lung cancer patients, should contain an increased frequency of rapid arylamine N-oxidation phenotypes with the frequency of acetyltransferase phenotype being greater or perhaps the same as in the control group.
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PMID:Aromatic and heterocyclic amine metabolism and phenotyping in humans. 195 28

Methylxanthines enhance lethality of alkylating agents in human cancer cells, a phenomenon attributed to the prevention of DNA repair. Pentoxifylline is a nontoxic methylxanthine, used clinically for claudication. Using human cancer cells in culture or in a mouse xenograft model, we studied combination treatments with alkylating agents and pentoxifylline or other methylxanthines. With human bladder cancer cells in culture, cytotoxicity of thiotepa was increased up to 10-fold (P less than 0.01) by posttreatment with pentoxifylline, with a major clinical metabolite of pentoxifylline, or with caffeine; the pentoxifylline concentrations required (0.4-1.0 mM) are clinically achievable in the bladder after nontoxic p.o. doses. With human bladder or breast cancer xenografts in a modified subrenal capsule assay, enhancement of thiotepa was also observed by in vivo posttreatment with pentoxifylline. In contrast, these combinations produced no increased toxicity to normal tissues in these animals, measured by weight, lethality, or histological changes of the normal bladder urothelium. These results provide evidence for a novel approach to improve the therapeutic index of thiotepa and other alkylators, used for topical therapy of bladder cancer and, possibly, systemic therapy of other malignancies.
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PMID:In vivo and in vitro enhanced antitumor effects by pentoxifylline in human cancer cells treated with thiotepa. 313 25

A case-control study of diet and bladder cancer was conducted during 1979-1982 in Edmonton, Calgary, Toronto, and Kingston, Canada. A total of 826 histologically verified cancer cases were individually matched by age, sex, and area of residence to 792 randomly selected population controls. Subjects were interviewed concerning their histories of exposure to a number of dietary factors, including table-top artificial sweeteners, low calorie foods and drinks, beverages containing caffeine or ethanol, and certain other food items. Also, subjects provided information on their past medical, occupational, and residential histories, in addition to their exposures to tobacco and other life-style factors. For the analysis, conditional logistic regression methods were used. Under adjustment for cumulative lifetime amount of cigarette smoking, the dietary factors, with little exception, were not associated with significant alteration of risk for bladder cancer. In particular, ever regular use of artificial sweeteners did not appear to be associated with increased risk, either among men (odds ratio = 0.95, p = 0.70) or among women (odds ratio = 1.15, p = 0.53). However, daily intake of cholesterol, calculated from reported frequencies of consumption of nine relevant food items, suggested a mild increase in risk; the odds ratio estimate of trend was 1.07/100 mg average daily intake (i.e., 1.07(5.5) = 1.45 for 550 mg cholesterol per day, as might be consumed in one egg; p = 0.009). A history of diabetes mellitus of onset after age 20 years also seemed to be associated with increased risk of bladder cancer (odds ratio = 1.65, p = 0.019), but this increase did not appear to be the result of use of insulin or other medications, or use of artificial sweeteners or low calorie foods. Thus, this study tends to confirm reports of a lack of association between use of artificial sweeteners and subsequent risk of bladder cancer.
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PMID:Dietary factors and the incidence of cancer of the urinary bladder. 336 17

During the years 1979-1981 a population-based case-control study of bladder cancer including papilloma was performed in greater Copenhagen. A total of 371 patients (280 males; 91 females), and a comparable age- and sex-stratified group of 771 controls (577 males; 194 females) remained for logistic regression analysis. Controls were selected at random from the general population of the study area. All persons were questioned about their drinking habits with respect to coffee, tea and other beverages, as well as their exposure to a number of known or suspected risk factors for bladder cancer. After adjustment for tobacco smoking, the relative risk of bladder cancer in relation to coffee drinking was not statistically significant among either men or women. A significant association was found between bladder cancer and tea drinking among men, but with no regular trend for increasing consumption. An association was found between risk of bladder cancer and both total daily liquid intake and non-cola soft drinks. This population-based case-control study provides no evidence of an isolated influence of coffee drinking or caffeine intake on bladder cancer risk.
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PMID:The Copenhagen case-control study of bladder cancer. II. Effect of coffee and other beverages. 369 28

Cytotoxicity of thiotepa or doxorubicin hydrochloride in human bladder cancer cells was investigated alone and in combination with methylxanthines. Methylxanthines can potentiate cytotoxicity of some DNA-damaging agents used in cancer therapy by preventing DNA repair. However, the potential clinical utility of these drug combinations has not been defined. Nontoxic concentrations of two methylxanthines, theobromine and caffeine, markedly enhanced lethality in T-24 human bladder cancer cells treated with thiotepa. Thiotepa cytotoxicity was increased over 10-fold by continuous treatment with nontoxic concentrations of methylxanthines (0.5 mM), but the major enhancing effect was observed in the 1st 24 hours after thiotepa exposure. By contrast, no such enhanced lethality was observed using higher methylxanthine concentrations and equal or greater cytotoxic treatments with doxorubicin hydrochloride. The amount of enhanced lethality by methylxanthines correlated directly with growth rate of the cells in culture, suggesting that differential enhanced therapeutic effects could be achieved in the treatment of superficial bladder tumors based on the increased proliferative rate of neoplastic bladder cells compared to normal bladder urothelium.
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PMID:Enhanced lethality by methylxanthines in human bladder cancer cells treated with thiotepa. 643 47

A case-control study of bladder cancer in two northern counties of New Jersey was conducted to investigate a tumour that has been considered to be strongly associated with industrial and environmental exposures. The study population included 75 bladder cancer cases and 142 controls. Cases and controls were matched for race, sex, age, place of birth and place of residence. Statistically significant associations with bladder cancer and risk ratios of greater than 2.0 were found for cigarette smoking and for working in dye, petroleum (fuel) or plastics industries. No statistically significant association was found for: cigar and pipe smoking; caffeine, saccharine and alcohol consumption; and life time occupational history of working in other than dye, petroleum and plastics industries. No statistically significant differences between cases and controls were found in family history of cancer. Risk ratios of at least 2.5 (but without statistical significance possibly because of sample size) were found for workers in rodenticide and printing industries, for cable workers and for cancer in the spouses of bladder cancer cases. Simultaneous multiple primary cancer sites were found in 9.3% of the bladder cancer patients; this is higher than the 0.2-8% reported in the medical literature. The life time occupational history of the bladder cancer cases points to industrial determinants: some are known (petroleum and dye industries) but the association with the plastics industry is new. If our findings are confirmed, investigations will be needed to determine whether any specific chemical or combination of chemicals used in the plastics industry is responsible for bladder cancer induction.
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PMID:Life time occupation, smoking, caffeine, saccharine, hair dyes and bladder carcinogenesis. 712 35

One hypothesis for the well known gender difference in bladder cancer risk is that males and females metabolize carcinogens differently. The caffeine breath test (CBT) was performed on a group of healthy men and women to determine whether there was a gender difference in P4501A2 activity. Results consistent with previous data suggest an elevation of CBT in men were observed, although this increase was not statistically significant. Among women, however, there was a significant difference between nulliparous and parous women(P = 0.03). Parous women had CBT values similar to men, whereas the results of women who had never given birth were lower. Confirming earlier studies, women taking oral contraceptives had low CBT values. Our data suggest an effect of recent caffeine consumption, with heavy coffee drinkers having higher rates of caffeine clearance. Adjustment for other weak effects, such as age, exposure to environment cigarette smoke, history of smoking, recent meat and cruciferous vegetable consumption, and use of alcohol or other medications, did not alter these findings. The finding of a difference between parous and nulliparous women requires further study.
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PMID:A study of gender-based cytochrome P4501A2 variability: a possible mechanism for the male excess of bladder cancer. 754 10

To determine which of the N-acetyltransferase (NAT) alleles [monomorphic (NAT1) or polymorphic (NAT2)] are expressed in the target cells for arylamine carcinogenesis, namely normal human uroepithelial cells, cDNA was prepared from cellular RNA and amplified by polymerase chain reaction (PCR), using upstream primer 1 comprising the 5' end (nt 47-68) and either downstream primers 2 (nt 908-889) or 3 (nt 953-931) corresponding with the 3' end. With primers 1 and 2, selective for NAT1, a characteristic 861 bp DNA fragment was obtained, whereas with primers 1 and 3, selective for NAT2, a characteristic 907 bp fragment was formed. Similarly, the PCR-amplified cDNA products from the SV40-immortalized human uroepithelial cell line were also found to contain both NAT1 and NAT2. Restriction fragment length polymorphism (RFLP) analysis with HincII (digesting NAT2 to produce 659 bp and 248 bp fragments) and HindIII (digesting NAT1 to produce a 786 bp fragment) further confirmed the authenticity of the NAT alleles. Furthermore, the NAT genotypes of 38 individuals were determined by PCR amplification of lymphocyte DNA and subsequent RFLP analysis using TaqI, KpnI and BamHI. The genotypes were compared to their in vivo acetylator phenotypes which were determined by measuring 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine following administration of caffeine. A good correlation between the genotype and phenotype was obtained in the study population and the frequency of NAT2 allele distribution was M1 > wild-type > M2 > M3. These results suggest that susceptibility to arylamine-induced bladder cancer might be influenced by both hepatic and bladder NAT and that the NAT genotype might be a useful biomarker for screening high risk individuals for bladder cancer resulting from exposure to arylamines.
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PMID:Expression of N-acetyltransferase (NAT) in cultured human uroepithelial cells. 800 Dec 35


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