RESUMO

BACKGROUND: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. OBJECTIVE: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. METHODS: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). RESULTS: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. CONCLUSION: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

Assuntos

Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Glioma/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Terpenos/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Basidiomycota/química , Linhagem Celular Tumoral , Glioma/metabolismo , Humanos

RESUMO

Circulating tumor DNA (ctDNA) has recently emerged as a minimally invasive "liquid biopsy" tool in precision medicine. ctDNA-genomic DNA fragments that are released into the bloodstream after the active secretion of microvesicles or tumor cell lysis reflects tumor evolution and the genomic alterations present in primary and/or metastatic tumors. Notably, ctDNA analysis might allow the stratification of patients, the monitoring of the therapeutic response, and the establishment of an opportunity for early intervention independent of detection by imaging modalities or clinical symptoms. As oncology moves towards precision medicine, the information in ctDNA provides a means for the individual management of the patient based on their tumor's genetic profile. This review presents current evidence on the potential role for ctDNA in helping to guide individualized clinical treatment decisions for patients with melanoma, castration-resistant prostate cancer, breast cancer, metastatic colorectal cancer, and non-small cell lung cancer.

Assuntos

DNA Tumoral Circulante/genética , Neoplasias/terapia , Medicina de Precisão/métodos , Humanos

RESUMO

Gastric cancer is the third leading cause of cancer-related death worldwide. To evaluate the anticancer potential and molecular mechanism of biflorin, a prenyl-ortho-naphthoquinone obtained from Capraria biflora L. roots, we used ACP02, a gastric cancer cell line established from a primary diffuse gastric adenocarcinoma. In this study, biflorin was shown to be a potent cytotoxic agent against ACP02 by Alamar Blue and Trypan Blue assays. Morphological analysis indicated cell death with features of necrosis. Furthermore, a decrease in colony formation, migration and invasion of ACP02 cells was observed after treatment with biflorin (1.0, 2.5 and 5.0 µM). Regarding the underlying molecular mechanism of biflorin in ACP02 cells, we observed a decrease in MYC expression and telomere length using FISH. Our findings suggest a novel molecular target of biflorin in ACP02 cells, which may be a significant therapeutic approach for gastric cancer management.

Assuntos

Antineoplásicos Fitogênicos/farmacologia , Naftoquinonas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Gástricas/metabolismo

RESUMO

MYC overexpression is considered a driver event in gastric cancer (GC), and is frequently correlated with poor prognosis and metastasis. In this study, we evaluated the prognostic value of genes upregulated by MYC in patients with GC. Metastatic GC cells (AGP01) characterized by MYC amplification, were transfected with siRNAs targeting MYC. RNA-seq was performed in silenced and non-silenced AGP01 cells. Among the differentially expressed genes, CIAPIN1, MTA2, and UXT were validated using qRT-PCR, western blot, and immunohistochemistry in gastric tissues of 213 patients with GC; and their expressions were correlated with clinicopathological and survival data. High mRNA and protein levels of CIAPIN1, MTA2, and UXT were strongly associated with advanced GC stages (P < 0.0001). However, only CIAPIN1 and UXT gene expressions were able to predict distant metastases in patients with early-stage GC (P < 0.0001), with high sensitivity (> 92%) and specificity (> 90%). Overall survival rate of patients with overexpressed CIAPIN1 or UXT was significantly lower (P < 0.0001). In conclusion, CIAPIN1 and UXT may serve as potential molecular markers for GC prognosis.

RESUMO

Depression is a mental disorder that affects 300 million people of all ages worldwide, but fewer than half of those with the condition receive adequate treatment. In addition, the high pharmacological refractoriness (affecting 30%-50% of patients) and toxicity of some classical antidepressants support the pursuit of new therapies. People with this condition show depressed mood, loss of pleasure, high levels of oxidative stress, and accelerated biological aging (decreased telomere length and expression of the telomerase reverse transcriptase (TERT), the enzyme responsible for telomere maintenance). Because of the close relationship between depression and oxidative stress, nutraceuticals with antioxidant properties are excellent candidates for therapy. This study represents the first investigation of the possible antidepressant and antiaging effects of commercial samples of clarified açaí (Euterpe oleracea) juice (EO). This fruit is rich in antioxidants and widely consumed. In this study, mice were treated with saline or EO (10 µL/g, oral) for 4 days and then with saline or lipopolysaccharide (0.5 mg/kg, i.p.) to induce depressive-like behavior. Only four doses of EO were enough to abolish the despair-like and anhedonia behaviors and alterations observed in electromyographic measurements. The antidepression effect of EO was similar to that of imipramine and associated with antioxidant and antiaging effects (preventing lipid peroxidation and increasing TERT mRNA expression, respectively) in three major brain regions involved in depression (hippocampus, striatum, and prefrontal cortex). Additionally, EO significantly protected hippocampal cells, preventing neuronal loss associated with the depressive-like state and nitrite level increases (an indirect marker of nitric oxide production). Moreover, EO alone significantly increased TERT mRNA expression, revealing for the first time a potent antiaging action in the brain that suggests neuroprotection against long-term age-related consequences.

Assuntos

Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Euterpe/química , Extratos Vegetais/química , Animais , Antidepressivos/química , Antidepressivos/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtorno Depressivo/patologia , Transtorno Depressivo/prevenção & controle , Euterpe/metabolismo , Frutas/química , Frutas/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Telomerase/genética , Telomerase/metabolismo , Regulação para Cima/efeitos dos fármacos

RESUMO

Aim: To analyze gene expression and copy number of five miRNAs (miR-1204, miR-1205, miR-1206, miR-1207 and miR-1208) localized in this chromosome region in gastric cancer (GC). Materials & methods: 65 paired neoplastic and non-neoplastic specimens collected from GC patients and 20 non-neoplastic gastric tissues from cancer-free individuals were included in this study. The expression levels of the five miRNAs were accessed by real time qPCR and were correlated. Results: MiR-1207-3p, miR-1205, miR-1207-5p and miR-1208 were upregulated in approximately 50% of GC tumors in relation to those of adjacent non-neoplastic tissues. MiR-1205 expression was associated with gain of gene copies and was upregulated in adjacent non-neoplastic samples relative to external controls. Conclusion: The coexpression of the 8q24 miRNAs indicated the role of miR-1205 in the initiation of gastric cancer development.

Assuntos

Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Gástricas/genética , Adulto , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima

RESUMO

Histone modifications regulate the structural status of chromatin and thereby influence the transcriptional status of genes. These processes are controlled by the recruitment of different enzymes to a specific genomic site. Furthermore, obtaining an understanding of these mechanisms could help delineate alternative treatment and preventive strategies for cancer. For example, in gastric cancer, cholecalciferol, curcumin, resveratrol, quercetin, garcinol and sodium butyrate are natural regulators of acetylation and deacetylation enzyme activity that exert chemopreventive and anticancer effects. Here, we review the recent findings on histone acetylation in gastric cancer and discuss the effects of nutrients and bioactive compounds on histone acetylation and their potential role in the prevention and treatment of this type of cancer.

Assuntos

Suscetibilidade a Doenças , Histonas/metabolismo , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Acetilação/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Dietética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Processamento de Proteína Pós-Traducional , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia

Assuntos

Aciltransferases/genética , Catecol O-Metiltransferase/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/enzimologia , Esquizofrenia/genética , Adulto , Brasil , Feminino , Humanos , Masculino

RESUMO

Aluminum and its compounds are common contaminants of water and food, as well as medications and cosmetics. The wide distribution of the element facilitates the demand for detailed studies of its biological and toxicological effects. This work aimed to evaluate the possible genotoxic and toxic activity resulting from in vivo and in vitro exposure to Al. For in vivo analysis, 40 Swiss mice were used, various concentrations of hydrated aluminum chloride were administered orally. They were analyzed for possible genic activity and metal cytotoxicity using a micronucleus test (MN), and for toxicity through histopathological evaluation of the extracted organs. For in vitro analysis, lymphocytes from the peripheral blood of 3 healthy donors were used. These cells were exposed to the same chemical agent in various concentrations. In vivo study revealed a significant increase in the number of MN in all Al concentrations. Furthermore, significant alterations in all the organs evaluated were verified by the presence of irreversible lesions (such as necrosis). Corroborating these findings, a significant increase in the quantity of MN in all concentrations with lymphocytes in vitro. In light of this, we suggest that this metal presents genotoxic potential and is potentially a cause of pathological disorders.

Assuntos

Compostos de Alumínio/toxicidade , Cloretos/toxicidade , Dano ao DNA , Linfócitos/efeitos dos fármacos , Adolescente , Cloreto de Alumínio , Compostos de Alumínio/administração & dosagem , Animais , Cloretos/administração & dosagem , Feminino , Humanos , Masculino , Metais/toxicidade , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Adulto Jovem

RESUMO

Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied.

RESUMO

Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione - AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione - AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl)-1,3-thiazolidine-2,4-dione - AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2,4-dione - AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin-eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways.

Assuntos

Acridinas/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Fragmentação do DNA/efeitos dos fármacos , DNA Topoisomerases Tipo I/metabolismo , Tiazolidinedionas/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Ensaio Cometa , Humanos , Microscopia de Fluorescência , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Telomerase/antagonistas & inibidores , Telomerase/metabolismo

RESUMO

PURPOSE: Gene expression array analysis is providing key data on the potential candidate genes and biological pathways involved in schwannoma origin and development. In this way we performed expression array studies on tumor-related genes in schwannomas. METHODS: The GE Array Q Series HS-006 (SuperArray, Bethesda, MD, USA) was used to determine the expression levels of 96 genes corresponding to 6 primary biological regulatory pathways in a series of 23 schwannomas. RESULTS: We identified 15 genes down-regulated, primarily corresponding to signal transduction functions, and 26 genes up-regulated, most frequently involving cell adhesion functions. CONCLUSIONS: In addition to the NF2 inactivation (considered as an early step), variations of other biological regulatory pathways might play a key role in schwannoma.

Assuntos

Perfilação da Expressão Gênica , Neurilemoma/genética , Humanos , Neurilemoma/patologia , Análise de Sequência com Séries de Oligonucleotídeos

RESUMO

Medulloblastoma is a highly cellular malignant embryonal neoplasm, being the most common malignant pediatric brain tumor, accounting for 20-25 % of pediatric central nervous system tumors. To investigate the effect of the TP53 Arg72Pro single-nucleotide polymorphism (SNP) on clinicopathological and phenotypic parameters, we performed a case-controlled study of 122 patients and 122 healthy controls from Brazil. No significant associations were found between the TP53 Arg72Pro genotypes and the clinicopathological parameters studied. Compared with Arg/Arg, which is the most common genotype in the study population, both the Arg/Pro and Pro/Pro genotypes did not influence the medulloblastoma development risk [odds ratio (OR) = 1.36 and P = 0.339 for the Arg/Pro genotype; OR = 1.50 and P = 0.389 for the Pro/Pro genotype]. With regard to prognosis, disease-free survival was not significantly different among the TP53 Arg72Pro SNP genotypes (P > 0.05), but the less frequent genotype (Pro/Pro) was associated with shorter overall survival of medulloblastoma patients (P = 0.021). These data suggest that, although there is no association between the TP53 Arg72Pro SNP and medulloblastoma risk, the Pro/Pro genotype is associated with shorter overall survival of patients submitted to adjuvant therapy. Nevertheless, due to the interethnic composition of the Brazilian population, future studies on larger populations from other parts of the world are essential for a definitive conclusion on the function of the TP53 Arg72Pro SNP.

Assuntos

Neoplasias Cerebelares/genética , Genes p53/genética , Predisposição Genética para Doença/genética , Meduloblastoma/genética , Polimorfismo de Nucleotídeo Único , Brasil , Estudos de Casos e Controles , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/terapia , Quimiorradioterapia Adjuvante , Criança , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Meduloblastoma/mortalidade , Meduloblastoma/terapia , Reação em Cadeia da Polimerase , Prognóstico , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética

RESUMO

(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the phenstatin family. This compound has been studied due to its potent cytotoxicity and ability to inhibit tubulin assembly. The present study aimed to evaluate the mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in human lymphocytes with an IC50 value of 5.68 µM, and therefore, concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 µM were used for all protocols. The alkaline comet assay and chromosome aberration (CA) analysis were performed in different phases of the cell cycle (G1, G1/S, transition, and G2), to evaluate the DNA-damaging and clastogenic effects of PHT, respectively. CA analysis was carried out in the presence or absence of colchicine to evaluate the action of PHT in the mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with drug exposure in all phases of cell cycle. Interestingly, it induced an increase in mitotic index in experimental protocols without colchicine, corroborating its action as an antitubulin agent. It also induced DNA damage and was clastogenic with drug exposure in all phases of the cell cycle, in the presence or absence of colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects in human lymphocytes.

Assuntos

Benzofenonas/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Mutagênicos/toxicidade , Adulto , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ensaio Cometa , Feminino , Humanos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Masculino , Adulto Jovem

RESUMO

Despite the remarkable progress in the characterization of the molecular pathogenesis of glioblastoma multiforme (GBM), these tumors remain incurable and, in most cases, refractory to aggressive cytotoxic treatments. We conducted a morphological and cytogenetic study in two GBM cell lines (U343 and AHOL1), before and after treatment with pisosterol (at 0.5, 1.0 and 1.8 µg ml⁻¹), a triterpene isolated from the fungus Pisolithus tinctorius. No significant alteration was observed in the morphology and frequency of chromosomal abnormalities in the cell lines analyzed after treatment with pisosterol. Using fluorescence in situ hybridization analysis with a locus-specific probe for C-MYC showed that 72% of U343 and 65% of AHOL1 cells contained more than two alleles of C-MYC before treatment. After treatment, no effects were detected at lower concentrations of pisosterol (0.5 and 1.0 µg ml⁻¹). However, at 1.8 µg ml⁻¹ of pisosterol, only 33% of U343 cells and 15% of AHOL1 cells presented more than two fluorescent signals, suggesting that pisosterol blocks the cells with gene amplification. Cells that do not show a high degree of C-MYC gene amplification have a less aggressive and invasive behavior and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.

Assuntos

Antineoplásicos/farmacologia , Amplificação de Genes , Genes myc , Glioblastoma/patologia , Terpenos/farmacologia , Alelos , Basidiomycota/química , Linhagem Celular Tumoral , Aberrações Cromossômicas/efeitos dos fármacos , Humanos , Hibridização in Situ Fluorescente

RESUMO

BACKGROUND: This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics. METHODS: Dual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil. RESULTS: Deletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7-39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. The frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. The frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC. CONCLUSION: We suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types.

Assuntos

Adenocarcinoma/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 17/genética , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/patologia , Adulto , Idoso , Alelos , Brasil , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia

RESUMO

Epidermal growth factor (EGF) plays an important role in cancer. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of the EGF gene (+61 A>G) may influence its expression and contribute to cancer predisposition and aggressiveness. Aiming to investigate the role of EGF +61 A>G in the susceptibility to glioma and its prognosis, we performed a case-control study with 165 patients and 200 healthy controls from Brazil. Comparisons of genotype distributions and allele frequencies did not reveal any significant differences between the groups. The mean overall survival was 9.2 months for A/A, 8.2 months for A/G, and 7.7 months for G/G. When survival curves were plotted we found that the +61G allele is associated with poor overall survival (p=0.023) but not with disease-free survival (p=0.527). Our data suggest that, although there is no association between the EGF +61 A>G genotype and glioma susceptibility, this SNP is associated with shorter overall survival of glioma patients in the Brazilian population. Nevertheless, future studies utilizing a larger series are essential for a definitive conclusion.

Assuntos

Fator de Crescimento Epidérmico/genética , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Fator de Crescimento Epidérmico/fisiologia , Feminino , Genótipo , Glioma/etiologia , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco

RESUMO

Werner syndrome (WS) is a premature aging disorder characterized by early onset of symptoms related to normal aging and by a high predisposition to various types of cancer, including gliomas. WS is caused by inherited recessive mutations in the WRN gene, which encodes a helicase considered a caretaker of the genome. Aiming to study the role of WRN Cys1367Arg in glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of this single nucleotide polymorphism in 94 glioma patients and 100 healthy subjects. Comparisons of genotype distributions and allele frequencies did not reveal any significant difference between the groups. Overall and disease-free survival rates were calculated, but no statistically significant difference was observed. Our data suggest that WRN Cys1367Arg SNP is not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.

Assuntos

Arginina/genética , Cisteína/genética , Exodesoxirribonucleases/genética , Glioma/diagnóstico , Glioma/genética , Polimorfismo de Nucleotídeo Único/genética , RecQ Helicases/genética , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Frequência do Gene , Genótipo , Glioma/epidemiologia , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Risco , Análise de Sobrevida , Helicase da Síndrome de Werner

RESUMO

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Food Chem. Toxicol., 46 (2008) 1205, doi:10.1016/j.fct.2007.10.019. The duplicate article has therefore been withdrawn.