Effects of uracil calculi on cell growth and apoptosis in the BBN-initiated Wistar rat urinary bladder mucosa

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. (C) 1999 Wiley-Liss, Inc.

Mate attenuates DNA damage and carcinogenesis induced by diethylnitrosamine and thermal injury in rat esophagus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Papilomatose oral em cães: revisão da literatura e estudo de doze casos

Canine papillomatosis is an infectious viral disease characterized by oral, cutaneous or ocular papillomas, usually benign. The treatment is indicated in animals, with multiple tumors that produce pharyngeal obstruction, and problems, of eating or for aesthetic reasons. Different treatment protocols have been proposed, including surgical excision, cryosurgery, electro surgery, autogenous or recombinant vaccines, imunomodulators drugs, systemic and intralesional chemotherapy. In this study were reviewed the more important aspects of canine oral papillomatosis. In the 12 studied animals, the papillomas were observed predominantly in mouth, gum and palate regions, in puppies until 12 months, presenting combined infection with ehrlichiosis. The treatment using Propionibacterium acnes and/or autogenous vaccine showed efficacy in eight dogs (66.7%).

DNA methylation patterns of the CDHI, RARB, and SFN genes in choroid plexus tumors

Genetic and epigenetic alterations in choroid plexus tumors, a rare neuroepithelial neoplasm most frequently detected in children, are poorly characterized. Epigenetic silencing associated with aberrant CpG island methylation is one mechanism leading to the loss of tumor suppressor functions in cancer cells. Using methylation-specific polymerase chain reaction, the methylation patterns of the genes CDH1 (E-cadherin), RARB (retinoic acid receptor, beta), and SFN (stratifin; 14-3-3 sigma) were retrospectively investigated in eight choroid plexus tumors (five papillomas, two atypical papillomas, and one carcinoma), as well as in two normal cortexes obtained after autopsy from male individuals aged 6 months and 64 years. Among the six pediatric tumors, the mean age at diagnosis was 1.8 years old (range, 0.2-6) and the two adult tumors were detected in a 66-year-old man and a 45-year-old woman. A high frequency of hypermethylation was detected in CDH1 and SFN genes in tumoral and normal cortex tissues. Tumor-specific RARB hypermethylation was observed in four papillomas. Further studies are required to evaluate the role of aberrant methylation in choroid plexus tumor progression. (c) 2007 Elsevier B.V. All rights reserved.

Medium-term protocols for in vivo evaluation of chemical modifiers of carcinogenesis

Cancer development is a long-term multistep process which allows interventional measure before the clincial disease emerges. the detection of natural substances which can block the process of carcinogenesis is a important as the identification of anti-tumoral drugs since they might be used in chemoprevention of cancer in high-risk groups. In vivo rodent models of chemical caecinogenesis have been used to study plant-derived inhibitors of carcinofenesis such as indols, coumarins, isothiocyanates, flavones, phenols and allyl-sulfides. Since the standard in vivo rodent bioassay is prolonged and expensive, shorter reliable protocols are needed. Two in vivo medium-term protocols for evaluation of modifiers of carcinogenesis are presented, one related to liver and the other to bladder cancer. Both protocols use rats, last 8 and 36 weeks and are based on the two-step concept of carcinogenesis: initiation and promotion. The protocols use respectively the development of altered foci of hepatocytes expressing immunochistochemically the placental form of gluthation S-transferase and the appearence of pre-neoplastic urothelium and papillomas as the end-points. the use of these protocols for detection of plantpderived inhibitors of carcinogenesis appear warranted.

Absence of promoting potential of bracken fern (Pteridium aquilinum) in rat urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and uracil

Conventional studies on bracken fern (Pteridium aquilinum; PA) carcinogenicity have used high dietary concentrations (around 30%) and long-term exposure (up to 52-70 weeks) without consideration of the multistep character of the chemical carcinogenesis process. The present study evaluated specifically the promoting potential of 3-5% dietary crude PA in the rat urinary bladder mucosa in a 32-week-long initiation-promotion assay for chemical carcinogenesis. Initiation of urothelial carcinogenesis was accomplished with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Uracil (U) was provided through the diet in order to expand the population of initiated cells. Seven groups (C) of male Wistar rats were submitted to the following treatments: G1 = BBN (n = 8); G2 = U (n = 10); G3 = BBN-U (n = 9); G4 = BBN-PA-U-PA (n = 16); G5 = PA (n = 8); G6 = BBN-PA (n = 10); G7 = PA-U-PA (n = 12). At the end of the experiment rats presenting epithelial papillary or nodular hyperplasia (PNH), papillomas (PAP), or simultaneous PNH plus PAP numbered, respectively G1: 2-0-1; G2: 0-0-0; G3: 3-0-2; G4: 4-3-2; G5: 1-0-1; G6: 8-0-0; and G7: 0-0-0, with no significant differences in the incidence of lesions among the groups. More frequent and more severe lesions occurred in BBN-initiated animals, predominantly in those also exposed to uracil (G3 and G4). Low-dose crude bracken fern in the diet does not promote rat urinary bladder carcinogenesis after a 32-week period of exposure, even when the initiated urothelial cell population has been expanded through a mechanical stimulus. (C) 1995 Wiley-Liss, Inc.

Effects of uracil calculi on cell growth and apoptosis in the BBN- initiated Wistar rat urinary bladder mucosa

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.

Papilomavírus humano (HPV) em lesões benignas e malignas de mucosa oral pelos métodos de imuno-histoquímica e hibridização in situ

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Computer-assisted analysis of p53 and PCNA expression in oral lesions infected with human papillomavirus

OBJECTIVE: To carry out a retrospective study to determine whether human papillomavirus (HPV) infection and immunohistochemical expression of p53 and proliferating cell nuclear antigen (PCNA) are related to the risk of oral cancer. STUDY DESIGN: Fifty-seven oral biopsies, consisting of 30 oral squamous papillomas (OSPs) and 27 oral squamous cell carcinomas (OSCCs) were tested for the presence of HPV 6/11 and 16/18 by in situ hybridization using catalyzed signal amplification and in situ hybridization. p53 And PCNA expression was analyzed by immunohistochemistry and evaluated quantitatively by image analysis. RESULTS: Nineteen of the 57 oral lesions (33.3%) were positive for HPV. HPV 6/11 was found in 6 of 30 (20%) OSPs and 1 of 27 (3.7%) OSCCs. HPV 16/18 was found in 10 of 27 (37%) OSCCs and 2 of 30 (6.7%) OSPs. Sixteen of the 19 HPV-positive cases (84.2%) were p53 negative; 5 (9%) were HPV 6/11 and 11 (19%) HPV 16/18, with an inverse correlation between the presence of HPV DNA and p53 expression (P=.017, P < .05). PCNA expression appeared in 18 (94.7%) of HPV positive cases, showing that HPV 16/18 was associated with intensity of PCNA expression and with OSCCs (P=.037, P < .05). CONCLUSION: Quantitative evaluation of p53 by image analysis showed an inverse correlation between p53 expression and HPV presence, suggesting protein degradation. Image analysis also demonstrated that PCNA expression was more intense in HPV DNA 16/18 OSCCs. These findings suggest involvement of high-risk HPV types in oral carcinogenesis.

Expression of the nonclassical HLA-G and HLA-E molecules in laryngeal lesions as biomarkers of tumor invasiveness

Introduction: HLA-G and HLA-E are two nonclassical class I molecules, which have been well recognized as modulators of innate and adaptive immune responses, and the expression of these molecules in virus infected cells has been associated with subversion of the immune response. Objective: In this study we performed a cross-sectional study, systematically comparing the expression of HLA-G and HLA-E in benign, premalignant and malignant laryngeal lesions, correlating with demographic and clinical variables and with the presence of high-risk and low-risk HPV types. Materials and methods: Laryngeal lesions were collected from 109 patients and stratified into 27 laryngeal papillomas, 17 dysplasias, 10 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastases, 28 laryngeal carcinomas with metastasis along with their respective draining cervical lymph nodes, and 10 normal larynx specimens. The expression of HLA-G and HLA-E molecules was determined by immunohistochemistry. HPV DNA detection and typing was performed using generic and specific primers. Results: HLA nonclassical molecules showed a distinct distribution pattern, according to the larynx lesion grade. HLA-G expression increased in benign and premalignant lesions, and gradually decreased in invasive carcinomas and in respective draining cervical lymph nodes. Conversely, HLA-E expression increased as far as lesion grade increased, including increased molecule expression in the draining lymph nodes of malignant lesions. Only 17 (15.6%) patients were HPV DNA positive. Conclusions: Overexpression of HLA-E and underexpression of HLAG appear to be good markers for malignant larynx lesion.

Nucleotide and phylogenetic analysis of human papillomavirus types 6 and 11 isolated from recurrent respiratory papillomatosis in Brazil

There are few studies about the distribution of natural molecular variants of low-risk HPVs. Our aim was to evaluate the E6 early gene variability among HPV-6 and HPV-11 isolates detected in recurrent respiratory papillomatosis (RRP) samples obtained in a cohort of Brazilian patients. We also performed a phylogenetic analysis in order to compare nucleotide sequences identified in our study with previously reported isolates from different anatomic sites (laryngeal papillomas, genital warts, cervical cancer and anal swabs) obtained from other parts of the world to determine the phylogenetic relationships of variants detected in Brazil. The complete coding region of the E6 gene of 25 samples was cloned and sequenced: 18 isolates of HPV-6 (72%) and 7 isolates of HPV-11 (28%). A total of four different HPV-6 genomic variants and two HPV-11 genomic variants was identified. It was not possible to correlate specific variants with disease severity. Phylogenetic trees for both HPV types were constructed enclosing both E6 sequences detected in our study and formerly published sequences. In both phylogenetic trees, the sequences from Brazil did not group together. We could not establish a geographical association between HPV-6 or HPV-11 variants, unlike HPV-16 and HPV-18. © 2013 Elsevier B.V.

Antígenos leucocitários humanos não-clássicos HLA-G e HLA-E em lesões benignas, pré-malignas e malignas de laringe associadas à infecção pelo Papilomavirus Humano (HPV)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise do gene E6 de HPV de baixo risco em papilomatose de laringe

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the International Programme on Chemical Safety framework

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise da variabilidade genética e expressão de HPV em papilomatose de laringe

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)