Tumors bladder cancer

DAC (decitabine) I Advanced solid tumors, bladder cancer, breast cancer, male breast cancer, melanoma NCI/USC... 

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. 

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. 

It is recommended that daily saccharin intake be maintained below 1 g because of a risk of bladder cancer. A lifetime daily diet containing 5-7.5% saccharin has induced bladder tumors in rats [69]. However, it is probable that saccharin is only a very weak carcinogen in humans. The amount contained in pharmaceutical preparations is well below the recommended maximum human daily intake. 

Bladder tumor-associated antigen (BTA), a human complement factor H, is produced by bladder cancer cells (men two to three times as often as women). Cancer cells are sometimes seen in urine samples by microscope cytoscopy (examination of the bladder with an instrument inserted into the urethra), which can reveal abnormal areas. Biopsy is needed to confirm the diagnosis. Early stage cancer confined to the bladder wall can often be removed with a cytoscope. If several tumors are present, they are removed by infusing the bladder with a solution containing bacteria able to stimulate the immune system. 

The most common BTA test is an immunoassay-based assay that uses monoclonal antibodies to detect the presence of bladder tumor-associated antigen in urine. In clinical studies, the BTA test was compared with cytoscopy-voided urine for the detection of recurrent bladder cancer. The sensitivity of BTA appeared su-... 

Intravesical infusion of linear PEI/pDNA polyplexes was evaluated in patients with superficial bladder cancer where intravesical therapy with bacillus Calmette-Guerin had failed [6, 224]. Patients had low grade superficial bladder cancer, which expressed H19. The therapeutic pDNA contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. Escalating doses of 2-20 mg plasmid per intravesical treatment were applied, with responders continuing to receive polyplexes once a month every month for 1 year. The treatment resulted in complete ablation of the marker tumor, without any new tumors in four of the 18 patients (22% overall complete response rate). Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. 

The answer is i. (Katzwng, p 984.) Bacille Calmette-Guerin vaccine is a nonspecific stimulant of the reticuloendothelial system. It is an attenuated strain of Mycobacterium fruvis that appears most effective in small, localized bladder tumors. This agent is approved for intravesicular use in bladder cancer. Adverse reactions are associated with the renal system, such as problems with urination, infection, and cystitis. 

Historically, bladder tumors have been associated with exposures in the aniline dye industry. However, conclusive evidence for any one particular exposure could not be obtained in these studies since the workers were exposed to many chemicals within the same work area. For example, Case et al. (1954) investigated the incidence of bladder tumors among British workers in the chemical dye industry. In addition to aniline, the workers were exposed to other aromatic amines, including a- and P-naphthylamine, benzidine, and auramine. Although exposures could not be quantified, there was insufficient evidence to suggest that aniline was a cause of bladder cancers. More recent studies indicate that P-naphthylamine, 4-aminodiphenyl, 4-nitrodiphenyl, 4,4-diaminodiphenyl, or o-toluidine may be involved in increased cancers in the dye industry (Ward et al. 1991 Benya and Cornish 1994). 

It is of more than a little interest to note that the sites of tumor formation do not always match across species. Benzidine, a substance once widely used in dye manufacture, was shown many years ago to be a carcinogenic risk for the bladder in workers exposed to excessive levels. The rat bladder is not responsive to this substance, but its liver is. It wasn t until Wilhelm Hueper turned to the dog that bladder cancer could be reproduced in a laboratory animal. It is now understood that benzidine metabolism is similar in dogs and people, and that metabolism in the rat takes a different course. It is also understood that certain benzidine metabolites, and not benzidine itself, are the proximate causes of tumors. Knowledge of metabolic differences helps explain the species similarities and differences in tumor response. If we had available the rat data and no human data, we would be in error to conclude that benzidine was a cause of human liver cancer. 

In a 30-year follow-up of a cohort of 984 workers employed at a benzidine manufacturing facility there was a significant excess of bladder tumors among men with the highest estimated level of benzidine exposure. The bladder cancer risk declined in those first employed after 1950, when preventive measures were instituted. 

No excess of bladder tumors was found in men with known exposures to PBNA at a rubber tire factory. From 1946 to 1970, there were 9 cases of bladder cancer among 4177 men vs. 10.0 expected of these 4177 workers, 3301 had known exposures to PBNA. These results contrast with those involving exposures before 1949, when workers at the factory also... 

The use of 5-FU in combination with radiotherapy has shown improved survival in various malignancies including unresectable pancreatic cancer, resectable pancreatic cancer, Dukes B2 and C rectal cancer, esophageal cancer, and hepatobiliary cancer (Table 2). Similarly, 5-FU with concurrent radiation has also been used for organ preservation in different tumors involving bladder cancer, anal cancer, and laryngeal cancer (Table 3). 

These studies were followed by others that demonstrated the potential for therapeutic enhancement by combined cisplatin-radiation treatments with primary murine bladder cancer (60), EMT-6 mammary tumors and KHT and RIF-1 sarcomas (61), and Lewis lung carcinoma (62). 

Early clinical studies clearly demonstrated that cisplatin could be administered safely and concurrently with radiation therapy (73-75). Early clinical trials that demonstrated the promise of the combination of cisplatin and radiation therapy included the treatment of brain tumors (76,77), head and neck tumors (78), malignant melanoma (79), and bladder cancer (80). Early clinical trial integrating carboplatin administration with radiation therapy was carried out in patients with locally advanced nonsmall cell lung cancer (NSCLC) (81). A hypothesis put forth by Coughlin and colleagues (81) was that the best clinical outcomes would be achieved with the combination of cisplatin and radiation therapy in tumors that were responsive to cisplatin. 

Pagano F, Bassi P, Galetti TP, Meneghini AM, Milani C, Artibani W, Garbeglio A. Results of contemporary radical cystectomy for invasive bladder cancer a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. J Urol 1991 145 45-50. 

Bladder cancer is the fifth most common malignancy in men. Approximately 70% of cases present with superficial disease and 30% have muscle-invasive tumors or metastatic disease. Radical surgery remains the standard treatment for invasive disease. Following cystectomy for muscle invasive bladder cancer, up to 50% of the patients will develop distant metas-tases (see Sternberg, 1995). 

TGFa-PE4o (TP40) Tissue growth factor-alpha (TGF-a) Binds to TGF receptors overexpressed on solid tumors PE40 is a binding-deficient variant of PE Cytotoxicity Evaluated in phase I testing for bladder cancer [106]... 

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