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

In a comparative study of tryptophan metabolism and urinary excretion of nucleic acid derivatives (including beta-aminoisobutyric acid, 7-methylguanine, pseudouridine, and urate) in 12 male bladder cancer patients, the excretion of pseudouridine and 7-methylguanine decreased significantly after an oral dose of 2 g L-tryptophan. A similar decrease occurred after an oral nicotinamide load of 50 mg four times a day, which indicated a possible common mode of action of tryptophan and nicotinamide. No definite resolution could be made as to the causal mechanism for the observed descrase in RNA turnover.
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PMID:Effect of tryptophan and nicotinamide loads on urinary excretion of RNA metabolites by bladder cancer patients. 14 44

The prognostic value of volume corrected mitotic index (M/V index) was improved in bladder cancer by correcting the M/V index for mean nuclear area (NA) in a section as an estimate of cellularity. The clinical follow-up data of 265 patients were obtained from patient files. The M/V index was counted in the biopsy specimens from the primary tumours and the NA was measured by means of IBAS 1&2 image analyser. The analysis showed that both M/V index and nuclear area corrected M/V index (MAM/V index) were related significantly to histological grade, clinical stage, papillary and progression in T-, N-, and M-categories (p less than 0.0001). In survival analysis NAM/V index was a better prognosticator (X2 = 25.5, p less than 0.0001) than M/V index (X2 = 14.4, p = 0.0007), due to better prediction of large celled high grade tumours. Recurrence-free period (RFP) was related significantly to NAM(V index (p = 0.0006) and to M/V index (p less than 0.0823)0 in that order. In conclusion, the correction of M/V index for NA as an estimate of cellularity in a section does not improve the prognostic value of M/V index in superficial bladder tumours, but it gives better grading results than the original M/V index in advanced tumours.
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PMID:How to count mitoses in bladder cancer grading? 206 37

Microsomal enzyme preparations from dog liver, kidney, and bladder were used to assess the prostaglandin H synthase-catalyzed activation of carcinogenic aromatic amines to bind covalently to proteins and nucleic acids. Benzidine, a urinary bladder carcinogen, bound to protein of bladder transitional epithelial and renal inner and outer medullary microsomes and was dependent upon addition of arachidonic acid, but not upon reduced nicotinamide adenine dinucleotide phosphate. Bladder transitional epithelial microsomes also activated o-dianisidine, 4-aminobiphenyl, and 2-naphthylamine to bind to protein and transfer RNA and benzidine and O-dianisidine to bind DNA. Cosubstrate and inhibitor specificities were consistent with activation by prostaglandin H synthase. Binding of benzidine to protein was not observed with either hepatic or renal cortical microsomes upon addition of arachidonic acid or reduced nicotinamide adenine dinucleotide phosphate. Prostaglandin H synthase and mixed-function oxidase-catalyzed bindings of 2-naphthylamine to protein and to transfer RNA were compared using liver and bladder microsomes. Only mixed-function oxidase-catalyzed binding was observed in liver, and only prostaglandin H synthase-catalyzed binding was observed in bladder. The rate of binding catalyzed by bladder microsomes was considerably greater than that catalyzed by hepatic microsomes. In addition, the bladder content of prostaglandin H synthase activity was approximately 10 times that of kidney inner medullary, a tissue reported to have a relatively high content of this enzyme in other species. These results are consistent with involvement of bladder transitional epithelial prostaglandin H synthase in the genesis of primary aromatic amine-induced bladder cancer.
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PMID:Metabolic activation of carcinogenic aromatic amines by dog bladder and kidney prostaglandin H synthase. 642 34

Nitric oxide synthase (NOS) immunohistochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry were used to investigate the distribution of nitroxergic, i.e., nitric oxide-synthesizing, neuronal perikarya and processes in the human ureterovesical junction (UVJ). Tissue specimens obtained from two cadaver kidney donors and two patients undergoing radical cystectomy for bladder cancer were examined. Clusters of NOS-immunoreactive neurons were localized in extramural ureterovesical ganglia. NOS-containing nerve fibers traveled within large extramural nerve trunks and marched among smooth muscle bundles. Extramural and intramural blood vessels were encircled by varicose NOS-positive axonal processes. The distribution of NOS immunoreactivity paralleled the staining pattern for NADPH-d activity. Urothelium stained strongly for NADPH-d activity but showed no NOS immunolabeling. Specimens from all four patients investigated showed similar staining patterns. Our results suggest that nitric oxide, a potent smooth-muscle-relaxing neurotransmitter in the autonomic nervous system, plays a physiologic role in opening the human UVJ.
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PMID:Nitroxergic innervation of the human ureterovesical junction. 748 46

Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia-modifying agents during radical radiotherapy for bladder cancer using a standard daily 20-fraction schedule. Three groups of patients have received (a) nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in 20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4 weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4 weeks. Ten patients were treated in each group. All patients completed carbogen and radiotherapy as prescribed, but only 45% completed daily nicotinamide over the 4-week treatment period. The end points of this study were acute bowel and bladder morbidity and local control at cystoscopy 6 months after treatment. An expected level of acute bowel and bladder morbidity was seen that reverted to normal in most patients by 12 weeks with no difference between the three treatment groups. Complete response rates at 6 months were seven out of ten (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It is concluded that carbogen and nicotinamide may improve the results of daily fractionated radiotherapy in bladder cancer and that further evaluation is required.
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PMID:Carbogen and nicotinamide in the treatment of bladder cancer with radical radiotherapy. 923 29

In tryptophan metabolites, 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been reported to show a carcinogenic action to mice bladder and the relation of the metabolites to human bladder cancer has been discussed. We developed methods for the fluorometric assay of these compounds and showed that the excretion of 3-hydroxyanthranilic acid increased in the patients with bladder cancer. We also devised methods for the fluorometric assay of glucuronide and sulfate of 3-hydroxyanthranilic acid and showed that the minor excretion of these conjugated forms was shown in humans. The distribution of these compounds was also studied and the obtained data suggests that 3-hydroxykynurenine has affinity for the pancreas. We then developed methods for the determination of other metabolites of tryptophan. A fluorescence reaction with UV irradiation was found and applied to the determination. This method is the most sensitive to kynurenic acid but can be applied to kynurenine, nicotinamide and quinolinic acid. Furthermore, this methods also applied to the determination of some medicines, e.g. indomethacin, isoniazid, nalidixic acid, nicorandil and disodium cromoglicate in the serum or urine. We further devised other methods for the determination of xanthurenic acid and 5-hydroxyindoles.
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PMID:[Microanalysis of tryptophan metabolites]. 941 79

We developed methods for the fluorometric assay of 3-hydroxykynurenine and 3-hydroxy-anthranilic acid, which are suspected as carcinogens in bladder cancer. It was shown that the urinary excretion of 3-hydroxyanthranilic acid increased in patients with bladder cancer. We also developed methods for the fluorometric assay of glucuronide and sulfate of 3-hydroxyanthranilic acid and showed that the excretion of these conjugated forms was minor in humans. The distribution of 3-hydroxykynurenine was studied and data obtained suggested that it has an affinity for the pancreas. We then developed methods for determination of the related compounds of tryptophan. Fluorescence reaction with UV radiation was applied to the determinations of kynurenic acid, kynurenine, quinolinic acid, nicotinic acid, nicotinamide, N1-methyl-nicotinamide, isatin, xanthrenic acid, and melatonin in the serum or urine. Furthermore, the fluorescence reaction with UV radiation was applied to some drugs, e.g., indomethacin, isoniazid, naldixic acid, nicorandil, and disodium cromoglycate. The relationship was investigated between the tumor promoter, 12-tetradecanoyl-phobol-13-acetate (TPA), and delayed hypersensitivity in mice. The foot pad reaction (FPR) in mice was suppressed by the application of TPA following the application of 7,12-dimethylbenz[alpha]-anthracene (DMBA), a tumor initiator, in BALB/c mice, while the FPR was suppressed by the application of TPA alone in C3H/He mice. CD8+ and CD4+ T cells, which suppress the FPR, were induced in BALB/c and C3H/He mice, respectively. These T cells produced soluble factors that inhibited the FPR in mice.
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PMID:[Microanalysis of tryptophan metabolites and suppressor factor of delayed-type hypersensitivity in mice]. 1213 39

The use of definitive radiotherapy for treatment of invasive bladder cancer has the advantage of preserving bladder function, but tumour regression is only achieved in approximately 40-50% of patients. Knowledge of the molecular basis of sensitivity to ionizing radiation and identification of potential molecular predictors will provide useful information regarding patient response and thus help clinicians to individualize treatment. The recent application of cDNA expression array technology provides a useful tool to investigate hundreds or even thousands of genes in a single experiment. In our study, we have used the Atlas human stress cDNA array trade mark to investigate the expression profile of stress-related and DNA repair genes in a radioresistant bladder carcinoma cell line (MGH-U1) and its radiosensitive subclone (S40b). This provides an ideal situation to study genes related to radiation because the genotypes of both cell lines are basically similar and differential changes detected are likely to be related to the different radiosensitivity phenotype. Of 234 genes blotted on the array, 3 genes (Heat shock protein 90, Heat shock protein 27 and Nicotinamide N-methyl transferase) showed consistent downregulation in the radiosensitive clone in 2 independent experiments. These results were further confirmed for HSP27 and NNMT using Sybr Green I-based real-time QRT-PCR. The role of heat shock proteins (HSPs) in response to radiation remains to be determined; however, the results of our present work suggest a possible role of HSP27 in determining radiosensitivity. Our study also opens avenues for the investigation of genes, such as NNMT, which has not previously been linked to response to radiation.
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PMID:A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer. 1221 74

Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m(-2) pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P=0.0001) for GLUT1 and 0.74 (P<0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.
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PMID:GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. 1452 Apr 62

Cancer chemopreventive agents such as N-4-(hydroxyphenyl)retinamide (4HPR) are thought to prevent cancers by suppressing growth or inducing apoptosis in precancerous cells. Mechanisms by which these drugs affect cells are often not known, and the means to monitor their effects is not available. In this study endogenous fluorescence spectroscopy was used to measure metabolic changes in response to treatment with 4HPR in ovarian and bladder cancer cell lines. Fluorescence signals consistent with nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and tryptophan were measured to monitor cellular activity through redox status and protein content. Cells were treated with varying concentrations of 4HPR and measured in a stable environment with a sensitive fluorescence spectrometer. Results suggest that redox signal of all cells changed in a similar dose-dependant manner but started at different baseline levels. Redox signal changes depended primarily on changes consistent with NADH fluorescence, whereas the FAD fluorescence remained relatively constant. Similarly, tryptophan fluorescence decreased with increased drug treatment, suggesting a decrease in protein production. Given that each cell line has been shown to have a different apoptotic response to 4HPR, fluorescence redox values along with changes in tryptophan fluorescence may be a response as well as an endpoint marker for chemopreventive drugs.
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PMID:Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring. 1553 38


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