Bladder cancers

Aiming for a diagnostic urine test for transitional cell carcinoma (TCC, 95% of total cases), 94 samples and controls were analyzed. Of some 70 differentially expressed proteins and polypeptides in the 2-150 kDa mass range, 5 were preferentially expressed in TCC, at 3353 Da, 9495,44.6,100.120, and 133.190 kDa. The 3.3 kDa protein, also detected in microdissected bladder cells, was identified, by SELDI immunoassay and database search, as a member of the human defensin family. The diagnostic sensitivity of the combined markers was 78% compared to 33% of cytologic approaches [97]. 

Attempts to differentiate TCC from benign urogenital diseases led to a training sample set for a decision tree classification algorithm which, in turn, yielded a mass cluster pattern. In a blinded test set (n = 38) sensitivity was 96.3% and specificity was 87.0% [98]. In another study, a training set utilizing 5/187 mass peaks (from 104 urine samples) was used to establish a pattern for tree analysis. The pattern correctly predicted 49/68 test samples, 25/45 TCC samples, and 24/33 noncancerous samples [99]. 

An investigation of several methodological aspects of obtaining urinary protein profiles by SELDI-TOF-MS revealed that among the extrinsic factors instrument settings and matrix composition critically influenced peak detection and reproducibility, while freeze-thaw cycles had minimal effects. Intrinsic factors of significance included blood in urine, dilution, and first-void vs. midstream urine [100]. 

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Saccharin. Sacchatin [81-07-2] C H NO S, which is approximately 300 times as sweet as sucrose ia coaceatratioas up to the equivaleat of a 10% sucrose solutioa, has beea used commercially as a nonnutritive sweeteaer siace before 1900, predomiaanfly ia carboaated soft drioks, tabletop sweeteaers, and dietetic foods marketed primarily to diabetics. In 1977, the FDA proposed a ban on sacchatin because of its association with bladder cancer ia laboratory animals. At the time, it was the only commercially available nonnutritive sweetener, and pubflc outcry led to a delay of the ban, which was officially withdrawn ia 1991. Instead, the FDA required that warning labels be placed on all foods that contained the iagredient. Although sacchatin is heat stable, the pubflc debate over its safety, as well as the fact that approximately one-third of the population perceives it to have a bitter aftertaste, has limited its use. 

Other Sweeteners. Two other sweeteners, sucralose and cyclamates, are approved for use outside of the United States. Sucralose, a chlorinated derivative of sucrose which is 500—600 times as sweet as sugar, has received limited approval in Canada, and petitions for its approval are pending in the United States and Europe (71). Cyclamate sweeteners, once available in the United States, but now baimed because they caused bladder cancer in animals, are stiU available in Canada and Europe. Table 7 gives several examples of nonnutritive sweeteners that have been developed. 

A toxic component of braken fern, perhaps either quercetin (105) or ptaquiloside, a glucoside (106), has a mixed history of carcinogenicity. It is sometimes impHcated in an increased incidence of bladder cancer in animals and esophageal cancer in humans. Multiple other dietary components seem to either promote or interfere with its action, and the significance of braken fern in human carcinogenesis remains unproven. 

In 1969, a chronic toxicity study on a cyclamate saccharin (10 1) blend indicated bladder cancer problems in rats. Cyclamate was soon banned by the FDA, but saccharin remained an approved sweetener. In 1977, the FDA proposed a ban on saccharin because of the discovery of bladder tumors in some male rats fed with high doses of saccharin. Because no other nonnutritive sweetener was available at that time, the proposed ban faced strong opposition. 

The isothiazole ring does not occur in nature. By far the most important synthetic isothiazole derivative is saccharin. This was the first non-carbohydrate sweetening agent to be discovered, as long ago as 1879. It is about 300 times as sweet as sucrose, and is still used in many countries as a non-nutritive sweetener. After it was found that administration of massive doses to rats caused bladder cancer, its use was banned in the New World, but the controversy continues as to whether there is any danger when it is used in small quantity. Saccharin is also used as an additive in electroplating processes (73AHC(15)233). 

TABLE 5.8(b) Case-control Studies of Urinary Bladder Cancer annong Workers in the Printing Industry ... 

Cartwright, R. (1982). Occupational bladder cancer and cigarette smoking in West Yorkshire. Scand.J, Work Plnviron. Flealth 8 (Suppl. 1), 79-82. 

Gonii.alez, C., Lopez-Abente, G., Errezola, M., Escolar, A., Riboli, E., Izarzugaza, 1., and Nebot, iM. (1989). Occupation and bladder cancer in Spam a multi-centre case-control study. Ini. J. Epidemiol. 18, 569-577. 

Silverman, D. T., Levin, L. 1., Hoover, R. N., and Hartge, P. (1989). Occupational risk factors of bladder cancer in the United States I. White men. /. Natl. Cancer Inst. 81, 1472 -14SI, . Silverman, D. T, Levin, L. L, and Eloovet, R. N. (1990). Occupational risk factors of hladLler cancer among white women in the United States. Am. j. Epidemiol. 1.32, 453-461. 

Cordier, S., Clavel, J., Limasset, J. C., Boccon-Gibod, L., Le Moual, N., Manderenii, and Hemori, D. (1993). Occupational risks of bladder cancer in France A multicentre ca.se cimtml study, hit. I. Epidemiol. 22, 403-411. 

Sicmiarycki, )., Dewar, R., Nadon, L.., and Gerin, M. (1994). Occupational risk factors for bladder cancer Results from a case-control study in Montreal, Quebec, Canada. Am. J. Epide-miol. 140, 1061-1080. 

Coggoii, D., Pannett, B., and Ache.son, E. D. (1984). Use of job-exposure matrix in an occupational analysis of lung and bladder cancers on the basis of death certificates. /. Natl. Cancer Inst. 72, 61-65. 

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

Dead or live bacteria may be effective to stimulate inflammatory reactions of phagocytic cells against tumor cells. The best-characterized treatment is the use of Bacillus Calmette Guerin (BCG) in the case of bladder cancer where activation of the immune response is capable of controlling tumor growth. 

Bladder cancer Familial Ademomatous Polyposis (genetic pre-cancerous condition)... 

Wientjes MG, Badalament RA, An JL. Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer. Cancer Chemother Pharmacol 1993,32(4) 255-62. 

An update of a previous study (Axelson et al. 1978), Axelson (1986) evaluated an expanded cohort of 1,424 men (levels of trichloroethylene exposure inferred from measured urinary metabolite concentrations) and found a significant increase in incidences of bladder cancer and lymphomas, and a lower than expected incidence of total cancer mortality. A further update of this work (Axelson et al. 1994) expanded the cohort to include 249 women, tracking cancer morbidity over 30 years, and found no correlation between exposure concentration or exposure time and cancer incidence at any site. The highest standardized incidence ratio noted in this study was 1.56 (95% Cl of 0.51-3.64) for 5 cases of non-Hodgkin s lymphoma observed in men. Although four of these cases occurred in persons exposed for at least 2 years, and 3 cases had a latency of 10 years or more, urinary levels of TCA showed that 4 of the 5 cases were exposed to the lowest levels of trichloroethylene (urinary levels of TCA 0-49 mg/L). The study authors mentioned that a urinary TCA level below 50 mg/L corresponds to a trichloroethylene exposure concentration of about 20 ppm. The study authors concluded that "this study provides no evidence that trichloroethylene is a human carcinogen, i.e., when the exposure is as low as for this study population."... 

Lee, J.I. et al., Beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2 family and activation of caspases, Exp. Oncol., 28, 30, 2006. 

Carotenoids and urino-digestive cancers — On the whole, findings from epidemiological studies did not demonstrate a protective role of carotenoids against colorectal, gastric, and bladder cancers. Indeed, most prospective and case-control studies of colorectal cancer showed no association with dietary intake or plasma level of most carotenoids. - Only lycopene and lutein were shown to be protective against colorectal cancer. Otherwise, findings from the ATBC study s showed no effect of P-carotene supplementation on colorectal cancer. 

Garcia, R. et al.. High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer, Nutr. Cancer, 35, 212, 1999. 

Zeegers, M.P. et al.. Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk Results from the Netherlands Cohort Study, Br. J. Cancer, 85, 977, 2001. 

Carcinogenic agents include chemicals in the environment, such as aniline and benzene, which are associated with the development of bladder cancer and leukemia, respectively. Environmental factors, such as excessive sun exposure, also may result in cancer. Viruses, including the human papilloma virus and hepatitis B, maybe associated with the development of cancer. Some of the chemotherapy agents cause secondary cancers after therapy has been completed. Numerous factors may contribute to the development of cancer. 

CNS leukemia (IT) Breast cancer NHL Osteosarcoma Head and neck cancer Bladder cancer Rheumatoid arthritis... 

Wynder, E. L., Goldsmith, R., The epidemiology of bladder cancer-A second look, Cancer, 40, 1246, 1977. 

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