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Made available in DSpace on 2013-08-28T14:14:22Z (GMT). No. of bitstreams: 1 WOS000308192800001.pdf: 2114816 bytes, checksum: 95223cf44fe05f47a8fb9aa0655c8c35 (MD5) Made available in DSpace on 2013-09-30T18:42:11Z (GMT). No. of bitstreams: 2 WOS000308192800001.pdf: 2114816 bytes, checksum: 95223cf44fe05f47a8fb9aa0655c8c35 (MD5) WOS000308192800001.pdf.txt: 78755 bytes, checksum: ab6a867497af905a4892d1b3f9936875 (MD5) Previous issue date: 2012-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:01:18Z No. of bitstreams: 2 WOS000308192800001.pdf: 2114816 bytes, checksum: 95223cf44fe05f47a8fb9aa0655c8c35 (MD5) WOS000308192800001.pdf.txt: 78755 bytes, checksum: ab6a867497af905a4892d1b3f9936875 (MD5) Made available in DSpace on 2014-05-20T14:01:18Z (GMT). No. of bitstreams: 2 WOS000308192800001.pdf: 2114816 bytes, checksum: 95223cf44fe05f47a8fb9aa0655c8c35 (MD5) WOS000308192800001.pdf.txt: 78755 bytes, checksum: ab6a867497af905a4892d1b3f9936875 (MD5) Previous issue date: 2012-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) TP53 genes is one of more important tumor suppressor gene, which acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. The development of esophageal and gastric cancers is a multistep process resulting in successive accumulation of genetic alterations that culminates in the malignant transformation. Thus, this study highlights the participation of the main genetic alterations of the TP53 gene in esophageal and gastric carcinogenesis. Among these changes, high frequency of TP53 mutations, loss of heterozygosity (LOH), overexpression of the p53 protein, and consequently loss of p53 function, which would be early events in esophageal and gastric cancers, as well as an important biomarker of the prognosis and treatment response. Furthermore, Single Nucleotide Polymorphisms (SNPs) of TP53 have been implicated in the development and prognosis of several cancers, mainly TP53 codon 72 polymorphism whose role has been extensively studied in relation to susceptibility for esophageal and gastric cancer development. São Paulo State Univ, UNESP, Dept Biol, BR-15054000 Campus Sao Jose do Rio P, SP, Brazil Univ Sagrado Coracao, BR-17011160 Bauru, SP, Brazil São Paulo State Univ, UNESP, Dept Biol, BR-15054000 Campus Sao Jose do Rio P, SP, Brazil FAPESP: 12/13847-9

The polysaccharides beta-glucans occur as a principal component of the cellular walls. Some microorganisms, such as yeast and mushrooms, and also cereals such as oats and barley, are of economic interest because they contain large amounts of beta-glucans. These substances stimulate the immune system, modulating humoral and cellular immunity, and thereby have beneficial effect in fighting infections (bacterial, viral, fungal and parasitic). beta-Glucans also exhibit hypocholesterolemic and anticoagulant properties. Recently, they have been demonstrated to be anti-cytotoxic, antimutagenic and anti-tumorogenic, making them promising candidate as pharmacological promoters of health.

b-Glucan (BG) was tested in vitro to determine its potential clastogenic and/or anti-clastogenic activity, and attempts were made to elucidate its possible mechanism of action by using combinations with an inhibitor of DNA polymerase. The study was carried out on cells deficient (CHO-k1) and cells proficient (HTC) in phases I and II enzymes, and the DNA damage was assessed by the chromosomal aberration assay. BG did not show a clastogenic effect, but was anti-clastogenic in both cell lines used, and at all concentrations tested (2.5, 5 and 10 mg/mL) in combination with damage inducing agents (methylmethane sulfonate in cell line CHO-k1, and methylmethane sulfonate or 2-aminoanthracene in cell line HTC). BG also showed a protective effect in the presence of a DNA polymerase b inhibitor (cytosine arabinoside-3-phosphate, Ara-C), demonstrating that BG does not act through an anti-mutagenic mechanism of action involving DNA polymerase b.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:21:57Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:45:43Z : No. of bitstreams: 1 2-s2.0-33750738093.pdf: 130029 bytes, checksum: 89e0e1776930b35642c112d3857f20ee (MD5) Made available in DSpace on 2014-05-27T11:21:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-09-01 There is high interest in the natural products properties due to their use in popular medicine. Agaricus blazei Murrill ss. Heinem. (Ab) is native to Brazil and has been widely disseminated because its medicinal properties. In the present study, the genotoxic and antigenotoxic potential of Ab extracts were investigated using the comet assay. The cells utilized were the non drug-metabolizing line CHO-k1 (Chinese hamster ovary) and the drug-metabolizing line HTC (rat hepatoma). Cells were treated for 3 h in the absence of fetal bovain serum (FBS) with methanolic, hexanic and n-butanolic extracts at 50 μg/ml and 0.75% aqueous extract to test for genotoxicity. Antigenotoxic effects of extracts were determined in cells exposed to the DNA damage inducing agent ethyl methanesulfonate under simultaneous or simultaneous with 1 h pre-incubation conditions. The extracts did not show genotoxicity in HTC, while they were genotoxic in CHO-k1. No antigenotoxic effect was observed with any extract under any condition. These results demonstrate that the metabolism in presence or in absence has a direct influence on the genotoxicity of these extracts. © 2006 The Japan Mendel Society. Departamento de Biologia Geral Universidade Estadual de Londrina, Londrina-PR Departamento de Química Universidade Federal de São Carlos-UFSCar, São Carlos-SP Departamento de Patologia UNESP, Botucatu-SP Departamento de Patologia UNESP, Botucatu-SP

The Agaricus blazei Murill (ABM) mushroom, known as the sun mushroom, is native to Brazil and has become known for its medicinal properties. This study examined the anticlastogenic effect of Agaricus blazei in Chinese hamster ovary cells, CHO-k1, by means of a chromosome aberration test using methyl methanesulphonate (MMS, 10(-4)M) as the DNA damage inducing agent. Two mushroom lines were used, ABM 99/26 and ABM 97/11, and the latter was used in the young (Y) and sporulating (S) developmental phases. The cells were treated for 12 h with MMS alone or combined with aqueous extracts of A. blazei at a final concentration of 0.15%, which were prepared at three different temperatures: (a) hot (60 degrees C), (b) room temperature (25 degrees C) and (c) chilled (4 degrees C). Mushroom extracts showed a marked anticlastogenic effect against DNA damage, as evidenced by a decrease in the number of cells with breaks, regardless of the line used, or the developmental stage or the temperature at which the extract was prepared. Generally, the extracts were more effective in reducing the isochromatid type breaks. The data obtained suggest that extracts of A. blazei mushroom are anticlastogenic under the conditions tested, mainly during the G1 and S stages of the cell cycle, where chromosome breaks of the isochromatid type are produced by the MMS agent.

The present study aimed to evaluate apoptosis and cell proliferation alterations in esophageal benign lesions in comparison to esophageal carcinomas.Immunohistochemistry was performed for caspase-3 protein (CPP32) and Ki-67 antigen expression in the esophageal mucosa from patients with Chagas disease (CD) with and without megaesophagus (CM), chronic esophagitis (CE), esophageal carcinoma (ESCC) and in normal mucosa (NM).The Ki-67 labeling index (LI) was similar in all groups (range: 30%-48%), having no statistically significant difference among the groups. Positive CPP32 immunostaining was observed with similar frequency in the CD (30.8%), CM (30.4%) and CE (34.8%) groups, but it was increased in the ESCC group (55.5%); however, it was not statistically different from the other groups. No associations among the levels of CPP32 and Ki-67 expression were observed in the various groups, neither among parameters such as age, gender or alcohol and tobacco consumption.There were no evident changes in cell proliferation and apoptosis in benign lesions studied.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:05:03Z No. of bitstreams: 1 S1415-47572010000200001.pdf: 126276 bytes, checksum: 15c34ee7c0bb92be511ec06b7dfe672f (MD5) Made available in DSpace on 2013-08-22T19:05:03Z (GMT). No. of bitstreams: 1 S1415-47572010000200001.pdf: 126276 bytes, checksum: 15c34ee7c0bb92be511ec06b7dfe672f (MD5) Previous issue date: 2010-01-01 Made available in DSpace on 2013-09-30T20:08:43Z (GMT). No. of bitstreams: 2 S1415-47572010000200001.pdf: 126276 bytes, checksum: 15c34ee7c0bb92be511ec06b7dfe672f (MD5) S1415-47572010000200001.pdf.txt: 46032 bytes, checksum: 56bba2ce300cc7fd4ae857695f624379 (MD5) Previous issue date: 2010-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:00:40Z No. of bitstreams: 2 S1415-47572010000200001.pdf: 126276 bytes, checksum: 15c34ee7c0bb92be511ec06b7dfe672f (MD5) S1415-47572010000200001.pdf.txt: 46032 bytes, checksum: 56bba2ce300cc7fd4ae857695f624379 (MD5) Made available in DSpace on 2014-05-20T14:00:40Z (GMT). No. of bitstreams: 2 S1415-47572010000200001.pdf: 126276 bytes, checksum: 15c34ee7c0bb92be511ec06b7dfe672f (MD5) S1415-47572010000200001.pdf.txt: 46032 bytes, checksum: 56bba2ce300cc7fd4ae857695f624379 (MD5) Previous issue date: 2010-01-01 This review summarizes the chromosomal changes detected by molecular cytogenetic approaches in esophageal squamous cell carcinoma (ESCC), the ninth most common malignancy in the world. Whole genome analyses of ESCC cell lines and tumors indicated that the most frequent genomic gains occurred at 1, 2q, 3q, 5p, 6p, 7, 8q, 9q, 11q, 12p, 14q, 15q, 16, 17, 18p, 19q, 20q, 22q and X, with focal amplifications at 1q32, 2p16-22, 3q25-28, 5p13-15.3, 7p12-22, 7q21-22, 8q23-24.2, 9q34, 10q21, 11p11.2, 11q13, 13q32, 14q13-14, 14q21, 14q31-32, 15q22-26, 17p11.2, 18p11.2-11.3 and 20p11.2. Recurrent losses involved 3p, 4, 5q, 6q, 7q, 8p, 9, 10p, 12p, 13, 14p, 15p, 18, 19p, 20, 22, Xp and Y. Gains at 5p and 7q, and deletions at 4p, 9p, and 11q were significant prognostic factors for patients with ESCC. Gains at 6p and 20p, and losses at 10p and 10q were the most significant imbalances, both in primary carcinoma and in metastases, which suggested that these regions may harbor oncogenes and tumor suppressor genes. Gains at 12p and losses at 3p may be associated with poor relapse-free survival. The clinical applicability of these changes as markers for the diagnosis and prognosis of ESCC, or as molecular targets for personalized therapy should be evaluated. Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Biologia Laboratório de Citogenética e Biologia Molecular University of Colorado Medicine/Medical Oncology, Health Sciences Center Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Biologia Laboratório de Citogenética e Biologia Molecular

Models have suggested esophageal carcinogenesis can result from the alteration of sequences, leading to esophagitis, atrophy, dysplasia, carcinoma in situ and invasive carcinoma. While numerous genetic alterations have been reported in esophageal carcinogenesis, studies of benign lesions with precancerous potential are scarce.Immunohistochemistry was performed for p53, p16 and Fhit proteins in the esophageal mucosa from patients with Chagas disease (CD), chagasic megaesophagus (CM), chronic esophagitis (CE), esophageal squamous cell carcinoma (ESCC) and in normal mucosa (NM).The proportion of p53-positive cases increased progressively according to the severity of the pathology CD (7.7%), CM (26.1%), CE (522%) and ESCC (100%). However, p16 and Fhit did not show any statistically significant differences among the groups.p53 overexpression is involved in the initial steps of esophageal carcinogenesis, supporting further evaluation of its utility as a marker in precursor lesions, conversely, losses of Fhit and p16 expression may not be significant.

The mushroom Agaricus blazei is studied for its nutraceutical potential and as a medicinal supplement. The aim of the present study was to investigate the chemoprotective effect of beta-glucan extracted from the mushroom A. blazei against DNA damage induced by benzo[a]pyrene (B[a]P), using the comet assay (genotoxicity) and micronucleus assay with cytokinesis block (mutagenicity) in a human hepatoma cell line (HepG2). To elucidate the possible beta-glucan mechanism of action, desmutagenesis or bioantimutagenesis types, three treatment protocols were tested: simultaneous, pre-treatment, and presimultaneous. The results showed that beta-glucan does not exert genotoxic or mutagenic effect, but that it does protect against DNA damage caused by B[a]P in every protocol tested. The data suggest that beta-glucan acts through binding to B[a]P or the capture of free radicals produced during its activation. On the other hand, the pre-treatment results also suggest the possibility that beta-glucan modulates cell metabolism.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:05:00Z No. of bitstreams: 1 S1415-47572008000100021.pdf: 78956 bytes, checksum: 47e6639a24371f4c6004a2abbcc0173f (MD5) Made available in DSpace on 2013-08-22T19:05:00Z (GMT). No. of bitstreams: 1 S1415-47572008000100021.pdf: 78956 bytes, checksum: 47e6639a24371f4c6004a2abbcc0173f (MD5) Previous issue date: 2008-01-01 Made available in DSpace on 2013-09-30T20:08:37Z (GMT). No. of bitstreams: 2 S1415-47572008000100021.pdf: 78956 bytes, checksum: 47e6639a24371f4c6004a2abbcc0173f (MD5) S1415-47572008000100021.pdf.txt: 32471 bytes, checksum: 4b76650d16eda360ce4bb8dfe66a14e6 (MD5) Previous issue date: 2008-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:17:31Z No. of bitstreams: 2 S1415-47572008000100021.pdf: 78956 bytes, checksum: 47e6639a24371f4c6004a2abbcc0173f (MD5) S1415-47572008000100021.pdf.txt: 32471 bytes, checksum: 4b76650d16eda360ce4bb8dfe66a14e6 (MD5) Made available in DSpace on 2014-05-20T15:17:31Z (GMT). No. of bitstreams: 2 S1415-47572008000100021.pdf: 78956 bytes, checksum: 47e6639a24371f4c6004a2abbcc0173f (MD5) S1415-47572008000100021.pdf.txt: 32471 bytes, checksum: 4b76650d16eda360ce4bb8dfe66a14e6 (MD5) Previous issue date: 2008-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Functional food investigations have demonstrated the presence of substances that could be beneficial to human health when consumed. However, the toxic effects of some substances contained in foods have been determined. Reported medicinal and nutritive properties have led to the extensive commercialization of the basidiomycete fungi Agaricus blazei Murrill (sensu Heinemann), also known as Agaricus brasiliensis Wasser et al., Agaricus subrufescens Peck or the Brazilian medical mushroom (BMM). Different methanolic extract fractions (ME) of this mushroom were submitted to the cytokinesis-block micronucleus (CBMN) clastogenic assay and the hypoxanthine-guanine phosphoribosyl transferase locus (HGPRT) assay for gene mutation, both using Chinese hamster ovary cells clone K1 (CHO-K1). The results suggest that all the fractions tested possess cytotoxic and mutagenic potential but no clastogenic effects. Further information is needed on the biochemical components of the A. blazei methanol fractions to identify any substances with cytotoxic and/or mutagenicity potential. These findings indicate that A. blazei methanolic extract should not be used due to their genotoxicity and care should be taken in the use of A. blazei by the general population until further biochemical characterization of this fungi is completed. Universidade Estadual de Londrina (UEL) Departamento de Biologia Geral Universidade Federal de São Carlos (UFSCar) Departamento de Química Universidade Estadual Paulista Universidade Estadual Paulista

Agaricus blazei (Ab) has become popularly known for its medicinal properties. Scientifically, it has been tested with regard to its capacity to protect genetic material against damage. We examined different organic extracts (methanolic extract—ME, hexanic extract—HE and n -butanolic extract—BE) and an aqueous extract (AE) of Ab, for their capacity to induce DNA damage as well as for their protective effect. Genetic damage was determined by the chromosomal aberration assay (CA) in CHO-k1 cells for all extracts and the cytokinesis block micronucleus assay (CBMN) in non drug-metabolizing (CHO-k1) and drug-metabolizing (HTC) cell lines for extract BE only. The extracts did not show clastogenicity but showed anticlastogenicity. The greatest percent reduction obtained were with BE (105%) and AE (126%) treatments in CA. BE treatment did not display genotoxicity in CHO-k1, but was genotoxic in HTC. However, BE was shown to be antigenotoxic causing decreased micronucleus frequency in HTC and CHO-k1 cells. These results suggest that all the extracts contained protective substances, but in some cases they could show a genotoxic effect with regard to metabolism. Therefore, these findings warrant caution in the use of this mushroom by the population.

A fissura labiopalatina (FL/P) é uma das malformações craniofaciais mais comuns em humanos, com variação epidemiológica nas diferentes populações. Possui diferentes apresentações clínicas, divergindo de acordo com a extensão e estruturas acometidas, podendo acometer somente o lábio ou lábio e palato em conjunto, uni ou bilateralmente, de maneira completa ou incompleta ou apenas o palato (FP) tanto completa como incompletamente. Podem fazer parte de um quadro sindrômico, recebendo a denominação de FL/P sindrômica ou acontecer como um fenótipo isolado, sendo chamada de FL/P isolada ou não sindrômica. Em relação a etiologia da FL/P não sindrômica, a literatura afirma ser multifatorial com a predisposição genética associada a fatores ambientais. Apesar de se apresentarem frequentemente associadas, a FL/P e FP não sindrômicas são consideradas etiologicamente e embriologicamente distintas. Objetivo: Aprofundar e ampliar o conhecimento das FP isoladas não sindrômicas, descrevendo o fenótipo principal (FP isolada) e seus subfenótipos clínicos, investigando o fator genético relacionado à recorrência por meio do histórico familial e buscando elucidar possível fatores ambientais envolvidos por meio do histórico gestacional. Material e métodos: Foram coletados dados de 165 prontuários médicos de pacientes com FP isolada não sindrômica matriculados no Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de São Paulo (HRAC-USP). Para a coleta desses dados foram analisados segmentos do prontuário referentes a atendimentos realizados no HRACUSP em diferentes setores. Resultados: Em 165 pacientes estudados, o sexo feminino foi o mais acometido com 106 casos (64,24%) encontrados. O tipo de FP predominante foi a incompleta correspondendo a 88,48% da amostra total, sendo dentre elas a fissura de palato duro parcial a mais prevalente. Em cinco casos não foi possível realizar a classificação nos grupos referentes ao tipo de fissura adotados, sendo necessária a criação de um grupo de classificação adicional. Recorrência familial positiva foi relatada em 28,47% de 144 casos em que havia informação, e na maioria das vezes havia apenas 1 outro familiar acometido. A média da idade das mães e dos pais no momento da concepção foi de 26,9 e 31,4 anos, respectivamente. A porcentagem de abortos anteriores foi de 11,95% dos 92 casos informados e a consanguinidade foi de 3,29% dos 91 casos informados. A intercorrência mais frequentemente relatada (25 em 154 casos informados) foi o uso de medicamentos, tais como, antibióticos, anti-hipertensivos e medicamentos que auxiliam na prevenção do parto prematuro. Conclusão: O fenótipo FP isolada possui variações quanto à extensão de cometimento, sendo que as fissuras incompletas foram as mais frequentes e o sexo feminino predominantemente acometido. Em relação ao histórico familial e gestacional os dados que mais chamaram atenção estão relacionados ao percentual de recorrência familial (28,47%) e o uso de medicação durante a gestação. Cleft lip and palate (CL/P) is one of the most common craniofacial malformations in humans, with epidemiological variation in different populations. It has different clinical presentations that diverge according to the extension and affected structures, and may either affect the lip or lip and palate together, unilaterally or bilaterally, in a complete or incomplete way or just affect the palate (CP) completely or incompletely. CL/P can either be related to a syndrome, classified as syndromic CL/P or unrelated to a syndrome, occurring as an isolated phenotype, designated as isolated or nonsyndromic CL/P. Regarding the etiology of nonsyndromic CL/P, research indicates multifactorial causes with a genetic predisposition associated with environmental factors. Although it is often present in association, nonsyndromic CL/P and CP are considered embryologically and etiologically distinct. Objective: To deepen and broaden the knowledge of individual nonsyndromic CP, describing the main phenotype (isolated CP) and its clinical subphenotypes, investigating the genetic factors related to recurrence through family history and to elucidate possible environmental factors involving gestational history. Material and Methods: Data were collected from 165 medical patients records with isolated nonsyndromic CP enrolled at the Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de São Paulo (HRAC-USP). For data collection, segments of the records pertaining to care provided by HRAC-USP in different sectors were analyzed. Results: In the 165 patients studied, females were the most affected with 106 cases (64.24%) found. The predominant type of CP was incomplete corresponding to 88.48% of the total sample, and among these incomplete CP, the clefts involving partial hard palate were the most prevalent. In five cases it was impossible to classify the type of cleft, and the creation of an additional classification group was required. Positive familial recurrence was reported in 28.47% of 144 cases where information was available and in most cases there was only one other affected family member. The average age of mothers and fathers at conception was 26.9 and 31.4 years respectively. The percentage of previous miscarriages was 11.95% of the 92 reported cases and consanguineous marriage was found in 3.29% of the 91 reported cases. The most frequently reported complication (25 in 154 reported cases) was the use of drugs such as antibiotics, antihypertensives drugs, and drugs used to prevent premature birth. Conclusion: The phenotype Isolated CP presents variations in the extent of involvement, and incomplete clefts were the most frequent, with females predominantly affected. Regarding family history and gestational data what calls more attention were the percentage of familial recurrence (28.47%) and the use of medication during pregnancy.