RESUMO
The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.
Assuntos
Adenocarcinoma , Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Humanos , Adenocarcinoma/patologia , Adenoma Pleomorfo/metabolismo , Ciclina B1/metabolismo , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologiaRESUMO
Tumoral microRNAs, such as miR-125b and miR-155b, are important gene expression regulators with complex pathogenetic mechanisms. However, their role in DLBCL, especially when cell-of-origin classification is considered, are still to be elucidated. In a series of 139 DLBCL cases considering germinal center (GC) versus nonGC subtypes, we investigated miR-125b and miR-155b expression by in situ hibridization and their association with some immunophenotypic presentations, including MYC, BCL2 and TP53 expression, MYC, BCL2 and BCL6 translocation status, as well as clinicopathological features and outcomes. miR-125b detection was positively correlated to the Ki-67 index (P = 0.035) in the nGC. Considering the GC subgroup, the percentage of miR-125b positive cells was also correlated to either MYC and MYC/BCL2 double expression (P = 0.047 and P = 0.049, respectively). When it comes to nGC patients, miR-155b percentage and intensity, as well as Allred score, were positively correlated to disease progression (P = 0.038, P = 0.057 and P = 0.039, respectively). In a multivariate analysis, GC phenotype was a significant independent factor associated with higher OS (P = 0.007) and, considering the nGC group, although not significant, the expression of TP53, miR-125b and miR-155b seems to be potential prognostic biomarkers in these tumors. This study demonstrated different pathways based on cell-of-origin classification and highlighted different clinical outcomes. miR-125b, miR-155b and TP53 expression may also represent potential prognostic factors in nGC-DLBCL.
Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Humanos , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/uso terapêuticoRESUMO
OBJECTIVE: This study aimed to determine the presence of Epstein-Barr Virus (EBV) and Human papillomavirus (HPV) in breast cancer with patients from Northeast of Brazil, considering the molecular subtypes and also taking in account the relation with TP53 immunoexpression. METHODS: Seventy-five samples of invasive breast carcinoma with no special type were selected from pathology archives at Federal University of Ceará. EBV was detected by In situ hybridization (ISH) and immunohistochemistry (IHC) and HPV was detected by PCR. ISH was performed using EBER1 probe (Shibata et al., 1991; Bacchi et al., 1996) while IHC was performed on histological formalin-fixed paraffin-embedded tissue samples (Hsu et al., 1981). PCR methodology (Haws et al., 2004) was used to amplify the genetic material of human papillomavirus. The amplification products were electrophoretic analyzed on 1% agarose gel. The data analyses were carried out using the statistical software EPINFO® version 6.04d and SPSS version 17.0 (SPSS Inc., Chicago, IL). Statistically significant differences were evaluated by the chi-square test and Fisher's exact test and correlations between groups were analyzed by Spearman's and Pearson's rank correlation coefficient. RESULTS: 69.4% of the cases were EBNA1 positives by IHC. EBNA1 positive tumors had lower Ki-67 index (0-40%), while EBNA1 negative cases had relevant higher Ki-67 index (41-100%) (p = 0.06). EBV was present in all tumor grades, with a high frequency in grade I and III tumors comparing to EBNA1 negative cases. No HPV positive cases were observed. CONCLUSION: Regarding the results from this study, we support the hypothesis that EBV can be involved on breast tumorigenesis.
Assuntos
Neoplasias da Mama , Infecções por Vírus Epstein-Barr , Brasil/epidemiologia , Neoplasias da Mama/patologia , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Antígeno Ki-67 , Papillomaviridae/genéticaRESUMO
OBJECTIVE: This study aimed to evaluate the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) and the expression of p53, p16, E-cadherin, COX-2, MLH1, and MYC in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: One hundred OSCC specimens were submitted to in situ hybridization for HPV and EBV, and immunohistochemistry for detection of the human proteins. RESULTS: Thirty-one cases showed HPV in tumor tissue. EBV was not detected in any case investigated. The HPV(+) group demonstrated an increase of staining scores for nuclear p16 (p = .047), cytoplasmic MYC (p = .002), while a decrease for nuclear MLH1 (p = .048), suggesting that HPV may upregulate the expression of the first two proteins and down-regulate the latter. CONCLUSION: Our findings reinforce the hypothesis of the HPV-related oral carcinogenesis involving the expression of p16 and MYC, and MLH1 suppression. Exclusively cytoplasmic stainings for p16, MLH1, and MYC were also associated with more advanced tumors. Finally, in view of the lack of studies correlating the HPV or EBV infection to the expression of oncoproteins, more researches assessing a broader panel of markers and employing different approaches are still necessary in order to understand the role of these viruses as well as the molecular mechanisms involved in the development and progression of oral carcinomas.
Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Infecções por Papillomavirus , Alphapapillomavirus/metabolismo , Caderinas/metabolismo , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Humanos , Neoplasias Bucais/metabolismo , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor p53RESUMO
Stomach pathologies develop in a complex interaction between the host's genetic background and H. pylori virulent genes. Thus, our study aimed to compare active chronic gastritis (ACG), and intestinal metaplasia (IM) with inactive chronic gastritis (ICG), according to interleukin polymorphisms of IL6-174 G/C, IL8-251 A/T, IL1ß-511 C/T, and IL1RN VNTR taking into account patient gender and H. pylori genotypes. Interleukin polymorphisms were determined by RFLP-PCR and H. pylori genotype by PCR. IL6-174 GC and IL8-251 T allele showed a protective effect in women against ACG development and, conversely, IL8-251 polymorphism showed a risk for men. More virulent H. pylori strains were associated with the IL8-251 T allele and IL1ß-511 T allele in the AGC, and the vacA m1 allele and cagE gene from H. pylori was associated with the IM. Analysis of the progression of gastric lesions must take into account host variability genetic associated with genes H. pylori due to the relation between the virulent H. pylori genes and more severe gastric lesions, besides the relevance to the gender to IL6-174 and IL8-251 polymorphisms.
Assuntos
Helicobacter pylori , Interleucinas , Polimorfismo Genético , Feminino , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Interleucina-6/genética , Interleucina-8/genética , Interleucinas/genética , Masculino , Neoplasias Gástricas/microbiologiaRESUMO
OBJECTIVE: The aim of this study was to evaluate the expression of Twist and E-cadherin in lower lip squamous cell carcinoma (LLSCC) and their association with clinicopathologic parameters. STUDY DESIGN: Fifty-nine cases of LLSCC were analyzed by applying immunohistochemistry techniques in a semiquantitative manner. The systems proposed by Bryne etal., Brandwein-Gensler etal., and Almangush etal. were applied for analysis of the histopathologic malignancy grading system. RESULTS: Higher E-cadherin expression (general and membrane) was observed in cases presenting with disease-free survival after 5years of follow-up (P < .05). Higher Twist expression was observed in lesions classified as being in advanced stages, displaying recurrence, and having a high degree of malignancy. A significant negative correlation was detected between cytoplasmic Twist expression and membrane E-cadherin expression (Pâ¯=â¯.028). A statistically significant relationship was detected between high total Twist expression in tumors classified as high risk by Brandwein-Gensler etal., and no significant difference was observed among total, membrane, and cytoplasmic E-cadherin expressions in LLSCC cases and the 3 applied grading systems (P > .05). CONCLUSIONS: The results of the present study suggest the potential involvement of Twist and E-cadherin in the modulation of events related to worse prognoses in LLSCC cases.
Assuntos
Antígenos CD , Caderinas , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Labiais , Proteínas Nucleares , Proteína 1 Relacionada a Twist , Antígenos CD/metabolismo , Antígenos CD/fisiologia , Biomarcadores Tumorais , Caderinas/metabolismo , Caderinas/fisiologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Humanos , Lábio , Neoplasias Labiais/metabolismo , Neoplasias Labiais/patologia , Recidiva Local de Neoplasia , Proteínas Nucleares/metabolismo , Prognóstico , Proteína 1 Relacionada a Twist/metabolismoRESUMO
BACKGROUND/AIM: Breast cancer 1, early onset (BRCA1) gene is expressed in the cells of the breast and other tissues, where it plays a role in cell-cycle regulation, transcription, repair of DNA double-stranded breaks, ubiquitination, transcriptional regulation as well as other functions, such as cell response regulation to mitogenic signals triggered by estrogens. Considering that meningioma shows greater tumor growth during pregnancy, can express estrogen receptors and proliferate in response to estrogenic stimulation, the hypothesis that this type of tumor may share molecular mechanisms that involve exposure to estrogen should be investigated. Therefore, the aim of the present study was to investigate the BRCA1 gene methylation profile in meningioma. MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (PCR) assay was performed on 50 meningioma samples from male and female patients. Statistical analysis was carried out using Fisher's exact test. RESULTS: The most important finding of this study was that 100% of the male patients over 55 years with meningioma showed BRCA1 methylated in their tumor cells. CONCLUSION: The silencing of BRCA1 through hypermethylation seems to play an important role in meningioma.
Assuntos
Proteína BRCA1/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Feminino , Genes BRCA1 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Although the introduction of the perioperative chemotherapy on the management of gastric cancer has improved patients survival, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Thus, this study evaluated the tumor regression grading (TRG) in a series of post-treatment gastric tumors and its associations with HER2, MET, and FOXP3 expression. Material of 54 gastric cancer samples was available for TRG evaluation and immunohistochemistry. We found that total and subtotal pathologic response were significantly associated to the intestinal subtype (p = 0.04) and that well-differentiated tumors were significantly correlated with total or partial response (p = 0.019). Although not associated with the TRG, FOXP3 expression in gastric tumors was associated to poorly differentiated tumors (p = 0.03), to the diffuse and mixed subtypes together (p = 0.04) and to the presence of vascular infiltration (p = 0.04), while HER2 overexpression was associated to better differentiated cases (p = 0.04) and to the absence of vascular infiltration (p = 0.02). MET expression, however, showed no association with the analyzed clinicopathological factors. This study highlights the role of tissue differentiation on pathological response to neoadjuvant chemotherapy in gastric cancer and shows no impact between FOXP3, HER2 and MET expression in terms of TRG.
Assuntos
Adenocarcinoma/patologia , Fatores de Transcrição Forkhead/análise , Proteínas Proto-Oncogênicas c-met/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/patologia , Adenocarcinoma/química , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Gástricas/complicaçõesRESUMO
ß-Catenin exerts multiple functions in several neoplasms, playing a major role in cell signaling and tumor progression. This study analyzed possible CTNNB1 mutations in salivary gland pleomorphic adenomas (PAs) and adenoid cystic carcinomas (ACCs), and determined possible differences in ß-catenin immunoexpression in relation to these mutations, as well as histopathological aspects of these tumors. Twenty-four PAs (15 cell-rich and 9 cell-poor tumors) and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the analysis of ß-catenin distribution and cellular localization. Furthermore, ß-catenin expression was evaluated using the H-score scoring system. Mutations in CTNNB1 exon 3 were investigated by the single-strand conformational polymorphism test. Diffuse ß-catenin expression was more frequently observed in ACCs compared to PAs (P = 0.008). No significant difference in ß-catenin cellular localization was observed between these tumors (P = 0.098). Comparisons between PA and ACC cases revealed a higher median H-score in the latter (P = 0.036). Cell-rich PAs exhibited a trend for higher H-score than cell-poor tumors (P = 0.060), whereas lower H-scores were observed in cribriform ACCs when compared to tubular and solid ACCs (P = 0.042). Mutations in CTNNB1 were observed in 6 PAs and 7 ACCs, with no significant difference in H-scores for ß-catenin according to mutation status (P = 0.135). ß-Catenin is important in the pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations do not seem to significantly influence ß-catenin cytoplasmic/membranous expression or nuclear translocation in these tumors.
Assuntos
Adenoma Pleomorfo/patologia , Neoplasias das Glândulas Salivares/metabolismo , beta Catenina/genética , Adenoma Pleomorfo/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/imunologia , Carcinoma Adenoide Cístico/patologia , Humanos , Imuno-Histoquímica/métodos , Mutação , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/imunologia , beta Catenina/metabolismoRESUMO
Gastric cancer is the fourth most common type of cancer worldwide. Helicobacter pylori is a well-established risk factor and may cause injuries to genomic integrity through an inefficient DNA repair. This study aimed to examine the influence of polymorphisms in DNA repair enzymes using markers for microsatellite instability (MSI). Polymorphisms of DNA repair enzymes were detected by PCR-RFLP and MSI, by high resolution melt (HRM) analysis. Helicobacter pylori detection and genotyping were accomplished by PCR. MSI was observed in 47.5% of the cases and it was associated with the ERCC1 polymorphic allele, whereas MSI-H was associated with the XRCC3 heterozygous genotype. MSI was more frequent in intestinal gastric cancer (IGC), where it was associated with ERCC1 or RAD51 polymorphic alleles. Also, MSI-H was associated with the XRCC3 heterozygous. In diffuse gastric cancer (DGC), almost all of MGMT polymorphic genotype carriers showed MSI. Helicobacter pylori was positive in 94% of the cases and the most virulent strains were associated with MSI, mainly MSI-H. When the subtypes were considered, these associations were found only in the IGC and associated with more virulent strains. Among the cases with microsatellite instability, IGC showed a correlation between the XPD wild-type and the ERCC1 polymorphic allele, and all of them were infected by the most virulent strains. On the other hand, in DGC, the XPD polymorphic allele was correlated with the XRCC3 wild-type with no prevalence of H.pylori virulence. Our data demonstrated that polymorphisms in repair enzymes can interfere with the efficiency of the repair process, but it differs depending on the histological subtype and H.pylori involvement. Besides nucleotide excision repair, base excision repair and mismatch repair pathway, the homologous recombination are also involved.
Assuntos
Adenocarcinoma/genética , Enzimas Reparadoras do DNA/genética , Infecções por Helicobacter/genética , Instabilidade de Microssatélites , Neoplasias Gástricas/genética , Adenocarcinoma/microbiologia , Sequência de Bases , Reparo do DNA , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/microbiologiaRESUMO
OBJECTIVE: Despite their similar cellular origin, pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC) present distinct behaviors. This study aimed to analyze the immunoexpression of E-cadherin in PA and ACC of salivary glands, and to investigate differences in its expression in relation to E-cadherin gene (CDH1) -160C/A polymorphism. DESIGN: Twenty-four PA (15 cell-rich and 9 cell-poor tumors) and 24 ACC (10 tubular, 8 cribriform and 6 solid tumors) were selected for the analysis of pattern of distribution, and cellular localization of E-cadherin. In addition, E-cadherin expression was evaluated using the H-score scoring system. The CDH1 -160C/A polymorphism was investigated by PCR-RFLP. RESULTS: No significant differences in pattern of distribution (p=0.181) and cellular localization (p=0.192) of E-cadherin were observed between PA and ACC. Comparison of PA and ACC cases revealed a higher median H-score in the latter (p=0.036). Cell-rich PA presented a higher H-score than cell-poor tumors (p=0.013), whereas no significant differences in E-cadherin expression were observed between ACC subtypes (p=0.254). The heterozygous genotype of the CDH1 -160C/A polymorphism was detected in only one PA and one ACC. H-scores for tumors carrying the polymorphism were below the lower quartile of their respective groups. CONCLUSIONS: The results suggest that E-cadherin expression in PA and ACC is mainly related to cellular composition (epithelial cells versus myoepithelial cells) and degree of differentiation of myoepithelial cells in these tumors. The CDH1 -160C/A polymorphism does not seem to significantly influence the expression of E-cadherin in PA and ACC of salivary glands.
Assuntos
Adenoma Pleomorfo/genética , Caderinas/genética , Carcinoma Adenoide Cístico/genética , Neoplasias das Glândulas Salivares/genética , Adenoma Pleomorfo/metabolismo , Antígenos CD , Caderinas/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Eletroforese em Gel de Poliacrilamida , Genótipo , Humanos , Técnicas Imunoenzimáticas , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Neoplasias das Glândulas Salivares/metabolismoRESUMO
OBJECTIVE: In this study, single nucleotide polymorphisms (SNP) of interleukin (IL) 1ß -511C>T, IL1RN VNTR 86 bp, IL6 -174G>C, IL10 -819C>T and TNFα -308G>A were analyzed by PCR-RFLP with symptoms of dengue with the clinical features. SUBJECTS: 196 individuals admitted to the São José Infectious Diseases Hospital with suspected dengue infection. Dengue was confirmed in 111 of the patients. The control group consisted of 85 other individuals confirmed without dengue. RESULTS: It was demonstrated that the presence the T allele of IL1ß (P < 0.05) was associated with susceptibility to developing the disease. Other results also suggested that the polymorphism in the combinations IL6 × IL1ß (C and T alleles, respectively), IL1ß (T allele) × IL1RN (*2/*2 genotype), IL6 (C allele) × TNFα (A allele), IL10 (C/T genotype) × TNFα (A/A genotype) (P < 0.01, P = 0.01, P < 0.05 and P = 0.03, respectively) were associated with predisposition to developing the disease and its symptoms. CONCLUSIONS: In summary, the findings of this study in a Brazilian population point out the importance of studies of combinations of polymorphisms in the development of dengue, which can increase the risk of dengue infection and its severity.
Assuntos
Citocinas/genética , Dengue/genética , Predisposição Genética para Doença , Proteína Antagonista do Receptor de Interleucina 1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Brasil , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Dengue is an important infectious disease that has high morbidity and mortality rates in most tropical and subtropical areas of the world. The diversity of the clinical manifestations involved in the outcome of dengue virus infection is affected by the relationship between serotype/genotype of the virus, host immune status, host genetic background, and environmental factors. Polymorphisms in interleukin (IL) genes have been associated with risk of developing symptomatic dengue. This study aimed to determine the association of the single-nucleotide polymorphisms of IL1ß -511C>T, IL1RN 86 bp VNTR, and IL6 -174G>C genes with the clinical features of 198 individuals admitted to the São José Infectious Diseases Hospital with suspected dengue infection. Dengue was confirmed in 118 of the patients. The control group consisted of 80 other individuals who had symptoms similar to dengue, but negative for that. A higher frequency of increased hematocrit (p = 0.009), leukopenia (p = 0.000007), neutropenia (p = 0.0004), lymphocytosis (p = 0.00001), monocytosis (p = 0.004), atypical lymphocytes (p = 0.03), and thrombocytopenia (p = 0.0000009) was observed in the dengue patients. Among the polymorphisms studied, only IL1ß (-511C>T) was associated with dizziness, (p = 0.01), suggesting that IL1ß may be related to hypotensive episodes and increased vascular permeability. These results pointed out the importance of the IL1ß (-511C>T) polymorphism in the development of clinical symptoms of dengue symptomology.
Assuntos
Dengue/genética , Dengue/patologia , Predisposição Genética para Doença , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Helicobacter pylori (H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma. The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cagA and vacA genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cagA-negative. Several other virulence genes have been searched for, but these genes remain less well known that cagA and vacA. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and iceA based on the relevance shown in several studies in the literature.
Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Gastropatias/genética , Gastropatias/microbiologia , Animais , Aderência Bacteriana , Proteínas da Membrana Bacteriana Externa/genética , Gastrite/microbiologia , Ilhas Genômicas , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Inflamação/microbiologia , Úlcera Péptica/microbiologia , Estômago/microbiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Virulência , Fatores de Virulência/genéticaRESUMO
BACKGROUND: Gastric cancer results from a multifactorial process and is one of the most common causes of death worldwide. These tumors can arise in the distal stomach (non-cardia) and in the cardia region, presenting different characteristics and frequency of occurrence worldwide. AIMS: To search for differences between tumors of different locations that could explain the presence of cardia tumors, considering Helicobacter pylori strains and genetic polymorphisms. MATERIALS AND METHODS: DNA was extracted from gastric adenocarcinoma tissue of 127 patients. Helicobacter pylori genes were detected by PCR, and polymorphisms by PCR-RFLP. RESULTS: Most of the tumors were located in non-cardia. The genotype 28152GA of XRCC1 showed an increase in risk of cardia tumors. In analysis performed considering gender, women carrying TNF-308GA genotype showed a decreased risk of non-cardia tumors, while in men the decreased risk of non-cardia tumors was associated with TNF-308GG genotype. Genotypes combinations showed that the SNPs RAD51 135G>C, XRCC3 18067C>T, and XRCC1 28152G>A had some combinations more frequent in cardia tumors, with an increased risk. Patients infected by cagE-positive strains presented a positive correlation with non-cardia tumors. CONCLUSION: The results showed some susceptibility differences between tumors of different locations. There was an increased risk relationship between three repair enzyme SNPs and cardia tumors, and the G allele of the cytokine gene TNF negatively influenced the development of non-cardia tumors. Helicobacter pylori strains seemed to be different in the cardia region, where they were less virulent than those located in the distal region of the stomach.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/microbiologia , Cárdia , Helicobacter pylori/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Adenocarcinoma/patologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Feminino , Genes Bacterianos/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Rad51 Recombinase/genética , Fatores Sexuais , Neoplasias Gástricas/patologia , Fator de Necrose Tumoral alfa/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
INTRODUCTION: CCR5 receptor exerts an important role in the host immune response. Osteomyelitis is an inflammatory process and Staphylococcus aureus is the principal causative agent of this bone injury complication. A deletion of 32bp (CCR5Δ32) in the CCR5 gene seems to protect against HIV-1, S.aureus and other infections. However, the CCR5Δ32 allele has been associated with an increased risk for other diseases. OBJECTIVE: To investigate the function of CCR5 and to gather data about the relationship of the CCR5Δ32 mutation and the risk of developing osteomyelitis as a complication in patients with bone traumas. METHODS: In a study of 153 patients with bone traumas the presence of the CCRΔ32 mutation was determined by PCR. RESULTS: In this study, the CCR5Δ32 allele was present only in the heterozygous form. Osteomyelitis was more frequent in the wild type carriers (94.87%; 37/39) and most of the CCR5Δ32 carriers (87.5%; 14/16) did not present with osteomyelitis. CONCLUSION: The CCR5Δ32 could be associated with protection against osteomyelitis caused by S. aureus, corroborating the data from Alonzo & Torres study, in which CCR5 receptor is required for S. aureus leukotoxin ED (LukED) cytotoxicity.
Assuntos
Alelos , Mutação , Osteomielite/etiologia , Receptores CCR5/genética , Adulto , Idoso , Brasil , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Osteomielite/imunologiaRESUMO
Cervical cancer incidence has grown worldwide, with it being a more significant problem in developing countries. Invasive squamous cell cervical cancers are preceded by a long phase of preinvasive disease, known as cervical intraepithelial neoplasia. Cervical cancer can develop when the virus takes advantage of any TP53 gene dysfunction of the host organism. TP53 is responsible for encoding the tumor suppressor p53 phosphoprotein, which helps preserve genome integrity. Currently, many studies have focused on genetic polymorphisms as an important contribution to cancer susceptibility, but few related to cervical intraepithelial neoplasia (CIN). Thus, the present study aimed to see whether patients with suspected CIN had TP53 gene polymorphisms that might have contributed to the development of neoplasia. This study included 133 women who were referred to the Cervical Pathology Clinic of the Maternity School Assis Chateaubriand MEAC for suspected cervical lesions. Polymorphism genotyping was carried out by the PCR-RFLP technique using DNA extracted from patients' blood. The most frequent genotype in both CIN(+) and CIN(-) patients was Arg/Pro TP53 codon 72 and A1A1 for 16-bp Del in intron 3. No risk of cervical cancer was found for the polymorphisms studied. However, a significant association was found when the two polymorphisms were combined: patients with the A1A1/ArgPro genotype were statistically more frequent in the CIN(-) group (p = 0.042), while A2A2-A1A2/ProArg was significantly more frequent in the CIN(+) group. The results of our study suggest that combined analysis of TP53 polymorphisms Arg72Pro and 16-bp Ins/Del may help to monitor the development of CIN in Brazilian women.
Assuntos
Códon , Genes p53 , Predisposição Genética para Doença , Íntrons , Polimorfismo Genético , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Risco , Neoplasias do Colo do Útero/etiologiaRESUMO
The aim of the present study was to investigate the association between polymorphism in the interleukin-10 gene promoter at position -1082 in human immunodeficiency virus-infected patients who had presented allergic reaction due to efavirenz. The study included 63 patients treated at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. Twenty-one patients who had presented allergic reaction to efavirenz were compared to 42 patients with no allergic reaction following exposure to this drug. Blood samples were collected for DNA extraction and submitted to the restriction fragment length polymorphism - polymerase chain reaction technique. The -1082AA genotype was significantly more frequent in allergic patients as compared to non-allergic patients (p=0.019; χ(2)=5.534; OR=3.625; 95% CI=1.210-10.860). Likewise the allele IL-10 -1082A was identified significantly more often among efavirenz allergic patients than in the non-allergic group (p=0.009; χ(2)=6.787; OR=3.029; 95% CI=1.290-7.111). These findings suggest that the polymorphism in the interleukin-10 gene promoter -1082G/A can be related to the development of allergic reactions to efavirenz.
Assuntos
Benzoxazinas/efeitos adversos , Hipersensibilidade a Drogas/genética , Infecções por HIV/tratamento farmacológico , Interleucina-10/genética , Polimorfismo Genético/genética , Inibidores da Transcriptase Reversa/efeitos adversos , Adulto , Idoso , Alcinos , Benzoxazinas/uso terapêutico , Estudos de Casos e Controles , Ciclopropanos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto JovemRESUMO
The human papillomavirus (HPV) is an epitheliotropic agent whose high-risk genotypes have a well-established link with the development of cervical cancer. Although the relation of HPV to the oral squamous cell carcinoma (OSCC) has been studied since the beginning of the 1980s, its role in the oral carcinogenesis and the probable underlying molecular mechanisms are still not fully elucidated. We performed a systematic review of the worldwide scientific literature, published until the preparation of the present paper, concerning the association of HPV with OSCC, scrutinizing the samples, prevalence levels, the techniques utilized and relevant findings of the studies. The results showed that HPV is associated with approximately one quarter of OSCCs. Another interesting feature is the distinct pattern of infection in these oral tumors, including the participation of genotypes that are uncommon in cervical malignant lesions, such as HPV-38, 44, 53 and 70. Equally interesting is the possibility of carcinogenic action without the occurrence of viral integration, verified by the high expression of messenger ribonucleic acid (mRNA) of E6 and E7 from high-risk genotypes in cases whose virus remain in the episomal form. These findings support the assumption of HPV involvement in the genesis of OSCC, whereas warn about the possibility of unexpected viral behaviors that sometimes are not perceived or understood due to the technological limitations of the time and to the shortage of studies with the adequate approaches...
O papilomavírus humano (HPV) é um agente epiteliotrópico cujos genótipos de alto risco têm uma ligação já bem estabelecida com o desenvolvimento de cânceres cervicais. Embora a relação do HPV com o carcinoma de células escamosas oral (CCEO) venha sendo estudada desde o início da década de 1980, seu papel na carcinogênese oral e os prováveis mecanismos moleculares subjacentes ainda não estão completamente elucidados. Realizou-se uma revisão sistemática dos trabalhos existentes na literatura científica internacional até o momento da elaboração deste manuscrito concernente à associação do HPV com o CCEO, esquadrinhando as características das amostras, das prevalências verificadas, das técnicas utilizadas e os achados relevantes dos estudos. Os resultados demonstram que o HPV está associado a cerca de um quarto dos CCEO. Outro aspecto interessante refere-se ao padrão distinto das infecções nesses tumores orais, incluindo a participação de genótipos incomuns em lesões malignas cervicais, tais como HPV-38, 44, 53 e 70. Igualmente interessante é a possibilidade de atuação carcinogênica sem a ocorrência de integração viral, constatada pela elevada expressão de ácido ribonucleico mensageiro (RNAm) de E6 e E7, de genótipos de alto risco, em casos cujo vírus encontrava-se em estado epissomal. Essas evidências reforçam a tese do envolvimento do HPV na gênese dos CCEO, ao mesmo tempo em que alertam para a possibilidade de comportamentos virais inesperados que, por vezes, não são percebidos ou compreendidos devido à limitação tecnológica da época e à carência de estudos com abordagem apropriada...
Assuntos
Humanos , Carcinoma de Células Escamosas/etiologia , Infecções por Papillomavirus/complicaçõesRESUMO
Introdução: O Papilomavírus Humano (HPV) é um agente epiteliotrópico que apresenta mais de 100 genótipos.Destes, alguns são considerados de alto risco devido ao potencial para induzir o surgimento de lesões malignas, comoo carcinoma cervical, cujo percentual de associação com o referido vírus é de aproximadamente 90%. Nas célulasinfectadas, duas proteínas virais desempenham papel fundamental na tumorigênese. Objetivo: Realizar uma revisão dos trabalhos existentes na literatura científica internacional com enfoque no papel das proteínas virais do HPV na carcinogênese. Método: Os artigos utilizados para a realização da presente revisão foram selecionados e obtidos na íntegra nos portais eletrônicos Pubmed e Periódicos Capes. Os descritores utilizados na busca incluíram: Human Papillomavirus, HPV, viral proteins, E5, E6 e E7. Resultados: As proteínas virais E6 e E7 são amplamente conhecidas por promoverem a degradação das proteínas celulares p53 e pRb, respectivamente, efeito que responde por grande parte do potencial oncogênico dos genótipos de alto risco de HPV, sendo funcionalmente equivalentes a mutações dos referidos genes celulares, que são comumente observadas em diversos tumores. Contudo, novos estudos têm demonstrado que essas proteínas virais também estão envolvidas em diversas outras vias tumorais, denotando novamente a relevância das mesmas nesse processo. Ademais, alguns trabalhos apontam a proteína E5 como coadjuvante na carcinogênese. Conclusão: Os diversos efeitos constatados das proteínas precoces virais culminam no favorecimentoda proliferação celular descontrolada, imortalização, regulação da diferenciação celular, suscetibilidade à metástase e escape da vigilância imunológica