RESUMEN
The morphologic appearance and clinical behavior of the human urinary bladder papillary transitional cell carcinoma (TCC) probably result from a complex interaction between carcinogenic insults and host resistance during the patient's life. While the main recognized risk factors are of environmental origin (e.g. smoking), relatively little information exists about the susceptibility to TCC development. The human leukocyte antigen G (HLA-G) molecule plays an important role in immune response regulation and has been implicated in the inhibition of the cytolytic function of natural killer and cytotoxic T cells. Several lines of evidence indicate that HLA-G polymorphisms influence the expression level and production of different HLA-G isoforms. The aim of this study was to explore a possible influence of the HLA-G polymorphism on the susceptibility to urinary bladder TCC development and progression in smokers and nonsmokers Brazilian subjects. The HLA-G locus was found to be associated with susceptibility to TCC development and progression. The G*0104 allelic group (specially the G*010404 allele) and the G*0103 allele were associated with a tobacco-dependent influence on TCC development. The G*0104 group was associated with progression to high-grade tumors, irrespective of smoking habit, while the G*0103 allele was associated to high-grade tumor only in smoking patients. Our results are an evidence that the HLA-G locus itself, or as part of an extended haplotype encompassing this chromosome region (particularly the HLA-A given the high linkage disequilibrium observed between them in this data series), may be associated with TCC susceptibility and tumor progression, suggesting a tobacco-dependent influence of these polymorphisms.
Asunto(s)
Carcinoma de Células Transicionales/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Brasil , Carcinoma de Células Transicionales/etiología , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-G , Humanos , Mutación INDEL/fisiología , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Tabaquismo/complicaciones , Tabaquismo/genética , Neoplasias de la Vejiga Urinaria/etiologíaRESUMEN
The lymphoproliferative response and T lymphocyte subsets were evaluated at different stages of carcinogenesis in male Wistar rats sequentially initiated with N-diethylnitrosamine (DEN), N-butyl-N-4(hydroxybutyl)nitrosamine (BBN), N-methyl-N-nitrosourea (MNU), dihydroxy-di-N-propylnitrosamine (DHPN) and N, N'-dimethylhydrazine (DMH) (DMBDD initiation). One group was evaluated at the 4th week and other initiated group at the 30th week. Two initiated groups were also exposed through diet to 2-acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th until the 30th week. Two groups received only 2-AAF or PB until the 30th week. Five groups were studied to evaluate the effects of each initiator. The lymphoproliferative response was induced in vitro by concanavalin A and the percentage of T lymphocyte subsets was determined by flow cytometry. All groups submitted to initiation only, initiation plus promotion, or promotion only, developed significantly more preneoplastic lesions than the untreated control group. The main target organs for tumor development were the liver, colon, urinary bladder, kidneys and Zymbal glands, mainly in the group treated with DMBDD+2-AAF. There were no alterations of the lymphoproliferative response and of the T lymphocyte subsets percentage in the DMBDD-treated group at the 4th and 30th weeks. At the 30th week, the T lymphocyte subsets percentage was also not affected in the initiated groups after treatments with 2-AAF or PB. The lymphoproliferative response, however, was decreased in the DMBDD+2-AAF group and in the groups treated only with 2-AAF or PB. The present results indicate that the initiating chemicals used in the DMBDD initiation protocol do not exert any influence on the immune system. The alteration of lymphoproliferative response induced at the advanced stage of carcinogenesis without alteration of T lymphocyte subsets may indicate that the influence of 2-AAF and PB on the immune system is functional and not toxic.
Asunto(s)
Subgrupos de Linfocitos T/metabolismo , 1,2-Dimetilhidrazina/toxicidad , 2-Acetilaminofluoreno/farmacología , Alquilantes/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Butilhidroxibutilnitrosamina/toxicidad , Pruebas de Carcinogenicidad , Carcinógenos/toxicidad , Concanavalina A/farmacología , Dietilnitrosamina/toxicidad , Citometría de Flujo , Masculino , Metilnitrosourea/toxicidad , Neoplasias Experimentales/inducido químicamente , Nitrosaminas/toxicidad , Fenobarbital/farmacología , Ratas , Ratas Wistar , Bazo/efectos de los fármacos , Subgrupos de Linfocitos T/efectos de los fármacos , Distribución TisularRESUMEN
The interaction between dietary energy restriction and low dose of the fungicide hexachlorobenzene (HCB) was evaluated in a rat liver medium-term bioassay for carcinogenesis. Male Wistar rats were fed a control or a 50% energy-restricted diet, both added or not with 50 ppm HCB, for 6 weeks. HCB exposure or energy restriction separately did not exert any influence on the development of glutathione S-transferase placental form (GST-P(+)) foci of hepatocytes. Simultaneous HCB exposure and energy restriction induced a significant increase in liver centrilobular hypertrophy and GST-P(+) foci development. Our findings suggest that energy restriction increases liver response to low dose of HCB, unmasking the promoting potential of this fungicide.
Asunto(s)
Ingestión de Energía , Hexaclorobenceno/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Animales , Peso Corporal , Cocarcinogénesis , Fungicidas Industriales/toxicidad , Hígado/anatomía & histología , Hígado/enzimología , Masculino , Tamaño de los Órganos , Ratas , Ratas WistarRESUMEN
The different potential of initiated and non-initiated urinary bladder mucosa (UBM) to develop neoplasia was quantitatively evaluated in the male Wistar rat. Initiation of carcinogenesis was accomplished with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Stimuli for cell proliferation and apoptosis were obtained by exposure followed by withdrawal of 3% Uracil in the diet. The proliferation index (PI) was estimated in UBM immunostained for the proliferating nuclear cell antigen (PCNA). The apoptotic index (AI) and the density of papillary/nodular hyperplasia (PNH) were estimated in hematoxilin-eosin stained sections. PNH was the main proliferative response to the mechanical irritation by uracil, irrespective of previous initiation with BBN. Uracil exposure induced higher PI and PNH density in the initiated rats. After uracil withdrawal, there was a significant increase of the AI in both uracil-treated groups, which correlated well to the respective PNH density. However, at the end of the experiment, PNH incidence and density were significantly higher in the BBN-initiated mucosa, which also presented 18% incidence of papillomas and 27% of carcinomas. Therefore, under prolonged uracil calculi trauma, the UBM of BBN-initiated Wistar rats gives rise to epithelial proliferative lesions that progress to neoplasia through acquired resistance to apoptosis.
Asunto(s)
Butilhidroxibutilnitrosamina/toxicidad , Carcinógenos/toxicidad , Papiloma/patología , Uracilo/toxicidad , Cálculos de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Animales , Apoptosis , División Celular/efectos de los fármacos , Hiperplasia , Masculino , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología , Papiloma/inducido químicamente , Antígeno Nuclear de Célula en Proliferación/análisis , Ratas , Ratas Wistar , Vejiga Urinaria/efectos de los fármacos , Cálculos de la Vejiga Urinaria/inducido químicamente , Cálculos de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/inducido químicamenteRESUMEN
Malacoplakia is a granulomatous inflammatory disorder clinically and ultrasonographically very similar to prostatic adenocarcinoma. Symptoms and physical findings are similar to prostatism and in half of the patients the differential diagnosis includes malignancy, mainly because of the presence of a hard nodule on digital rectal examination. Additionally, cases of malacoplakia can show hypoechoic nodes on transrectal ultrasound mimicking adenocarcinoma. We report a case of malacoplakia of the prostate with emphasis on its similarities and differences with prostate adenocarcinoma.
Asunto(s)
Malacoplasia/diagnóstico , Neoplasias de la Próstata/diagnóstico , Anciano , Biopsia con Aguja , Diagnóstico Diferencial , Humanos , Malacoplasia/patología , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
The sediment from urinary bladder washings from 63 consecutive autopsies was cytologically studied in order to achieve a better understanding of the changes in urothelial cells collected from hospital populations. The observed alterations were correlated with alterations in the urinary system and with therapy preceding death. The specimens obtained were of good quality. In 39.7% of the cases, the sediment contained giant superficial multinucleated cells. Three of nine cases previously subjected to radiation or chemotherapy showed atypical urothelial cells. In three cases with immunosuppression, there was cytologic evidence of subclinical infection by polyomavirus, and virus particles were identified by electron microscopy of the vesical mucosa. The study of the smear background offered additional information: the sediment contained hyaline or hematic or hyaline-cellular casts in 17.4% of the cases, in all of which there were renal tubulopathies when the kidney sections were studied. The method is useful for a good evaluation of the autopsy as well as for training in urinary cytopathology.