Serum adenosine deaminase, catalase and carbonic anhydrase activities in patients with bladder cancer

OBJECTIVES: The relationship between adenosine deaminase and various cancers has been investigated in several studies. However, serum adenosine deaminase activity and carbonic anhydrase and catalase activities in patients with bladder cancer have not previously been reported. Therefore, the aim of this study was to measure serum adenosine deaminase, carbonic anhydrase and catalase activities in patients with bladder cancer. MATERIALS AND METHODS: Forty patients with bladder cancer and 30 healthy controls were enrolled in the study. Serum adenosine deaminase, carbonic anhydrase and catalase activities were measured spectrophotometrically. RESULTS: Serum adenosine deaminase, carbonic anhydrase and catalase activities were significantly higher in patients with bladder cancer than controls (all significant, p<0.001). CONCLUSIONS: These markers might be a potentially important finding as an additional diagnostic biochemical tool for bladder cancer.

Tabaquismo, Glutation S-Transferasa, N-Acetiltransferasa 2 y riesgo de cáncer de vejiga / Tabaquism, S-Transferase Glutation, N-Acetiltrasferase 2 and bladder cancer risk

El hábito tabáquico es el factor de riesgo más conocido para cáncer de vejiga. Ciertas arilaminas presentes en el cigarrillo han sido identificadas como carcinógenos para la vejiga en humanos. El objetivo de nuestro estudio es establecer el riesgo de padecer de cáncer de vejiga en individuos fumadores, acetiladores lentos para NAT2 y genotipos nulos de GSTM1 y GSTT1. Materiales y métodos: Se reunieron en total 150 pacientes, 75 pertenecientes al grupo de carcinoma urotelial de vejiga y 75 del grupo control, en este último no se incluyeron pacientes con enfermedad neoplásica de ninguna índole. El ADN se aisló de la muestra de sangre a partir de linfocitos utilizando un kit disponible comercialmente (QIAmp DNA Blood Mini and Maxi Kit, QIAGen GMBH). Mediante el uso de técnicas de reacción en cadena de polimerasa y de restricción/ fragmentación se determinaron los polimorfismos de las enzimas: NAT2, GSTT1 y GSTM1.Resultados: Se incluyeron un total de 150 pacientes, de los cuales 75 pertenecían al grupo controly 75 al grupo de cáncer de vejiga, la media de edad del grupo de cáncer de vejiga fue 60,5 +/-11,4 y del grupo control fue 51,3 +/- 11,4. En cuanto al género en grupo de cáncer de vejiga 64 por ciento pertenecían al sexo masculino. En el grupo control 41 por ciento pertenecían al sexo masculino. Al estudiar el hábito tabáquico se halló que 51 por ciento de los pacientes del grupo de cáncer de vejiga continuaban siendo fumadores, mientras que sólo 21 por ciento fumaba en el grupo control. En el análisis de los genotipos de la enzima NAT2 en el grupo de los pacientes con cáncer de vejiga 52 por ciento resultaron acetiladores lentos, y 4 por ciento acetiladores rápidos. En el grupo control 45 por ciento de los pacientes eran acetiladores lentos y 12 por ciento acetiladores rápidos. En cuanto a la determinación de GSTT1 19 por ciento de los pacientes del grupo de cáncer de vejiga y 24 por ciento del grupo control exhibieron el genotipo nulo...

Introduction: Smoking is the most studied risk factor for bladder cancer. Certain arilamines present in cigarettes have been identified as carcinogenic for the bladder in humans. The purpose of this study is to establish the risk of bladder cancer in smokers, slow acetilators for NAT2 and none active genotypes for GSTM1 and GSTT1. Material and methods: 150 patients were studied, 75 in the group of urothelial carcinoma of the bladder and 75 in the control group. The DNA was isolated from lymphocytes of blood samples using commercially available kit (QIAmp DNA Blood Mini and Maxi Kit, QIAG en GMBH). Enzyme polymorphisms of NAT2, GSTT1 and GSTM1 were determined using techniques of polymerase chain reaction and restriction/fragmentation. Results: 150 patients were included, of who 75 belonged to the control group and 75 had bladder cancer, the average of age of the bladder cancer group was 60.5 +/- 11.4 and of the control group 51.3 +/- 11.4. Regarding gender, in the bladder cancer group 64 percent were males. In the control group 41percent were males. 51 percent of the patients in the bladder cancer group continued being smokers, whereas only 21 percent smoked in control group. In NAT2 enzyme genotype analysis the bladder cancer group 52 percent were slow acetilators, and 4 percent fast acetilators. In the control group 45 percent were slow acetilators and 12 percent fast acetilators. Regarding GSTT1 determination, 19 percent of the bladder cancer group and 24 percent of the control group showed the non-active genotype. GSTM1 showed its non-active form in 44 percent of the bladder cancer group and 48 percent of the control group. Discussion: Bladder cancer is clearly related with smoking habit. We observed a very significant relationship when evaluating smoking habit, slow acetilators for NAT2, and none-active genotypes of GSTM1 and bladder cancer...

Telomerase activity: a potential marker of bladder transitional cell carcinoma in bladder washes

The enzyme telomerase maintains a constant telomere length in immortalized cells, allowing unlimited cell proliferation. Almost all cancer cells express telomerase activity. However, little data is available regarding the role of telomerase activity in the detection of bladder cancer with a bladder wash specimen. We detected telomerase activity in a bladder wash specimen of bladder cancer and normal tissues, and compared them with final pathologic diagnosis. Twenty-three patients with transitional cell carcinoma (TCC) of the bladder were enrolled in our study. A bladder wash specimen was obtained before transurethral resection of the bladder (TURB) and normal and cancer tissues from the same patients during TURB. Telomerase activity was analyzed in each specimen a using telomeric repeat amplification protocol (TRAP) assay based on polymerase chain reaction (PCR) technique. Cytologic diagnosis was performed using Papanicolaou's stain with cytocentrifuged cytology preparation. We observed telomerase activity in 95.7% (22/23) of bath cancer tissues and bladder wash specimens; only one case did not express telomerase activity. Telomerase activity was undetected in all normal tissues except one, which was obtained from a patient with carcinoma in situ. A total of 69.6% (16/23) of wash specimens were positive in cytopathologic diagnosis. The accuracy of cytopathologic diagnosis in pathologic grade 2 or 3 was relatively high (83.3%, 15/18). However, in five cases of grade 1 TCC only 20% (1/5) of cytologic diagnosis was positive whereas the telomerase activity of wash specimens was detected in 80% (4/5). Our data demonstrates that not only the majority of human bladder cancer tissues, but also the bladder wash specimens obtained from patients with TCC, expressed telomerase activity. It indicates that telomerase activity may be a reliable marker in detecting bladder cancer especially in cases with a low grade that bladder wash cytology can miss.

N-acetyltransferase activity--a susceptibility factor in human bladder carcinogenesis.

A higher proportion of slow acetylator phenotypes has previously been found among bladder cancer patients. In the present study carried out among 77 male bladder cancer patients and 80 non-cancer controls, 59.74% of the patients and 35% of the controls were slow acetylator phenotypes (p < 0.01). The odds of developing bladder cancer was also observed to be significantly higher among smokers than non-smokers (p < 0.01). The findings suggest that slow N-acetyl phenotype is a susceptibility factor in bladder carcinogenesis.

Modulation of thymidine kinase activity: a biochemical strategy to enhance the activation of antineoplastic drugs

Thymidine kinase is a key enzyme responsible for the activation of several anticancer and antiviral drugs. As the first enzyme in the salvage pathway of thymidine, it is regulated by the feedback inhibition exerted by the end-product of the pathway, namely thymidine 5'-triphosphate. 5'-Aminothymidine is a non-toxic analogue of thymidine capable of interfering with this regulatory mechanism. In fact, it has been shown that 5'-aminothymidine increases the cytotoxicity and metabolism of various thymidine analogues currently in use of the clinic as antineoplastic agents. This mini-review article focuses in the evidence supporting the role of 5'-aminothymidine as a potential prototype drug for a new class of anticancer agents: drugs which affect the regulation of key metabolic pathways that determine the efficacy of agents with cytotoxic activity. The mechanism of action, antineoplastic activities and basis for selectivity in tissue culture models are also described

CYP1A2 activity as a risk factor for bladder cancer

CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p< 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3-demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer.