Publications by authors named "Silvia Helena Barem Rabenhorst"

50 Publications

Detection of deletions in 1q25, 1p36 and 1pTEL and chromosome 17 aneuploidy in oral epithelial dysplasia and oral squamous cell carcinoma by fluorescence in situ hybridization (FISH).

Oral Oncol 2021 Feb 17;116:105221. Epub 2021 Feb 17.

Department of Oral Pathology, University of Fortaleza / Universidade de Fortaleza, School of Dentistry, Fortaleza, Brazil.

Objective: To identify chromosome deletions in 1q25, 1p36 and 1pTEL, and chromosome 17 ploidy status in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC).

Material And Methods: Samples from 57 OED and 63 OSCC were selected. FISH was performed using centromeric probes 17 and n LSIR 1p36/LSI 1q25 Dual Color Probe.

Results: In OED, deletions were found only in 1pTEL region (29.8%). In OSCC, there was a higher frequency of deletion in 1pTEL (79.4%), followed by 1p36 (73.0%), and 1q25 (20.6%). Advanced TNM clinical stages (III/IV) showed all the deletions studied; at early clinical stages (I/II) of OSCC, deletions were observed only in 1pTEL. The frequency of deletion in 1p36 was 17.0 times higher in OSCC at advanced clinical stages (PR: 17.00). The median number of cell nuclei with chromosome 17 aneuploidy was higher in OSCC than in OED (P < 0.001). Early clinical stages of OSCC showed lower median number nuclei with aneuploidy when compared to advanced tumors (P < 0.05). Tumors harboring deletions in 1p36, 1q25 and 1pTEL revealed higher median numbers of trisomic/polysomic nuclei when compared to lesions exhibiting no abnormalities in chromosome 1 (P < 0.05).

Conclusion: A higher prevalence of chromosomal abnormalities was found in OSCC than in OED, while in OSCC, higher abnormalities were present in lesions with higher TNM staging. 1pTEL deletion and monosomy of chromosome 17 are possible markers for progression of OED to OSCC. 1p36 deletion and trisomy/polysomy of chromosome 17 could be markers of worse prognosis of OSCC.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105221DOI Listing
February 2021

Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer.

Infect Genet Evol 2020 Oct 29;84:104477. Epub 2020 Jul 29.

Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address:

It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.
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http://dx.doi.org/10.1016/j.meegid.2020.104477DOI Listing
October 2020

Twist and E-cadherin deregulation might predict poor prognosis in lower lip squamous cell carcinoma.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 Apr 16;127(4):318-329. Epub 2018 Nov 16.

Professor, Postgraduate Program in Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address:

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 (P = .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.
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http://dx.doi.org/10.1016/j.oooo.2018.11.003DOI Listing
April 2019

Hypermethylation of Gene in Meningioma in Elderly Males.

Anticancer Res 2018 05;38(5):2819-2822

Molecular Biology Laboratory, Transfusion Blood Center, College of Agricultural Sciences, UNESP - Sao Paulo State University, Botucatu, Brazil

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.
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http://dx.doi.org/10.21873/anticanres.12526DOI Listing
May 2018

The association among HER2, MET and FOXP3 expression and tumor regression grading in gastric adenocarcinoma.

APMIS 2018 May;126(5):389-395

Division of Pathology, Instituto do Câncer do Ceará, Fortaleza, CE, Brazil.

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.
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http://dx.doi.org/10.1111/apm.12840DOI Listing
May 2018

Assessment of CTNNB1 gene mutations and β-catenin immunoexpression in salivary gland pleomorphic adenomas and adenoid cystic carcinomas.

Virchows Arch 2018 Jun 26;472(6):999-1005. Epub 2018 Mar 26.

Department of Oral Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

β-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 β-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 β-catenin distribution and cellular localization. Furthermore, β-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 β-catenin expression was more frequently observed in ACCs compared to PAs (P = 0.008). No significant difference in β-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 β-catenin according to mutation status (P = 0.135). β-Catenin is important in the pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations do not seem to significantly influence β-catenin cytoplasmic/membranous expression or nuclear translocation in these tumors.
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http://dx.doi.org/10.1007/s00428-018-2335-zDOI Listing
June 2018

The intricate interplay between MSI and polymorphisms of DNA repair enzymes in gastric cancer H.pylori associated.

Mutagenesis 2017 07;32(4):471-478

Laboratory of Molecular Genectic, Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.

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.
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http://dx.doi.org/10.1093/mutage/gex013DOI Listing
July 2017

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross-Reactive Nonsteroidal Anti-inflammatory Drug Hypersensitivity.

J Clin Pharmacol 2018 Jan 27;58(1):107-113. Epub 2017 Jul 27.

Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal do Ceara, Fortaleza, Brazil.

Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individual's susceptibility to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.
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http://dx.doi.org/10.1002/jcph.986DOI Listing
January 2018

A link between osteomyelitis and IL1RN and IL1B polymorphisms-a study in patients from Northeast Brazil.

Acta Orthop 2017 Oct 6;88(5):556-561. Epub 2017 Jul 6.

a Universidade Federal do Ceará , Fortaleza , Ceará , Brasil.

Background and purpose - Treatment failure of osteomyelitis can result from genetic susceptibility, highlighting polymorphisms of the interleukin-1 (IL-1) family members, central mediators of innate immunity and inflammation. Polymorphisms are DNA sequence variations that are common in the population (1% or more) and represent multiple forms of a single gene. We investigated the association of IL1RNVNTR (rs2234663) and IL1B-511C > T (rs16944) polymorphisms with osteomyelitis development in patients operated on because of bone trauma. Patients and methods - 153 patients who fulfilled the inclusion criteria were enrolled from a referral public hospital for trauma. All the patients were followed up daily until hospital discharge and, after this, on an outpatient basis. Patients were treated with prophylactic antimicrobials and surgery according to traumatology service protocol. The IL1RNVNTR and the IL1B-511C > T polymorphisms were determined by PCR and PCR-RFLP, respectively. Results - The IL1RN*2/*2 genotype was associated (OR: 7; p < 0.001) with a higher risk of osteomyelitis and was also significantly associated with Staphylococcus aureus infection. The haplotypes (combination of different markers) *2-C and *2-T were also associated with osteomyelitis development. Interpretation - IL1B-511C > T and IL1RNVNTR polymorphisms were associated with osteomyelitis development, which may have implications for patients with bone traumas. These data may be relevant for new therapeutic strategies for this disease.
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http://dx.doi.org/10.1080/17453674.2017.1348439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560221PMC
October 2017

Association of IL10, IL4, IFNG, and CTLA4 Gene Polymorphisms with Efavirenz Hypersensitivity Reaction in Patients Infected with Human Immunodeficiency Virus.

Jpn J Infect Dis 2017 Jul 28;70(4):430-436. Epub 2017 Feb 28.

Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará.

We evaluated interleukin-10 (IL10) -592 C/A, IL4-589 C/T, interferon gamma (IFNG)+874 A/T, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)+49 A/G gene polymorphisms associated with efavirenz hypersensitivity reaction. A total of 63 human immunodeficiency virus-positive patients under treatment at a public hospital were included in the study, of whom 21 presented with efavirenz hypersensitivity. Patients who presented with efavirenz hypersensitivity reaction showed a higher frequency of the IL10 -592A allele than the controls (p=0.028). The allele A was associated with increased risk of efavirenz hypersensitivity (odds ratio=2.40). In case of IL4, a significant difference in the frequency of the IL4 -589 (C/T) polymorphism was not observed between patients and controls. A significant inverse correlation was observed when comparing the CTLA4+49A/G and IL4 -589 C/T polymorphisms (r=-0.650, p=0.001); that is, the CTLA4 +49GG genotype, involved with the lowest capacity of inhibition, was inversely correlated IL4-589TT genotype, which induces high production of IL-4. With respect to the CTLA4+49A/G and IFNG+874T/A gene polymorphisms, significant differences in allele and genotype frequencies were not observed between the groups. Therefore, our data suggest that polymorphisms in regulatory regions of cytokine genes could modulate an individual's susceptibility to efavirenz hypersensitivity reaction.
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http://dx.doi.org/10.7883/yoken.JJID.2016.075DOI Listing
July 2017

Pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: E-cadherin immunoexpression and analysis of the CDH1 -160C/A polymorphism.

Arch Oral Biol 2017 Jan 15;73:48-54. Epub 2016 Sep 15.

Department of Oral Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.archoralbio.2016.09.005DOI Listing
January 2017

Association of genetic polymorphisms of IL1β -511 C>T, IL1RN VNTR 86 bp, IL6 -174 G>C, IL10 -819 C>T and TNFα -308 G>A, involved in symptomatic patients with dengue in Brazil.

Inflamm Res 2016 Nov 19;65(11):925-932. Epub 2016 Jul 19.

Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

Objective: In this study, single nucleotide polymorphisms (SNP) of interleukin (IL) 1β -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 IL1β (P < 0.05) was associated with susceptibility to developing the disease. Other results also suggested that the polymorphism in the combinations IL6 × IL1β (C and T alleles, respectively), IL1β (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.
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http://dx.doi.org/10.1007/s00011-016-0975-5DOI Listing
November 2016

Association of Polymorphisms in IL1β -511C>T, IL1RN 86 bp VNTR, and IL6 -174G>C Genes with Clinical Dengue Signs and Symptoms in Brazilian Dengue Patients.

Viral Immunol 2016 Jul-Aug;29(6):372-6. Epub 2016 May 26.

2 Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará , Ceará, Brazil .

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 IL1β -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 IL1β (-511C>T) was associated with dizziness, (p = 0.01), suggesting that IL1β may be related to hypotensive episodes and increased vascular permeability. These results pointed out the importance of the IL1β (-511C>T) polymorphism in the development of clinical symptoms of dengue symptomology.
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http://dx.doi.org/10.1089/vim.2015.0082DOI Listing
January 2018

What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases.

World J Gastroenterol 2015 Oct;21(37):10563-72

Débora Menezes da Costa, Eliane dos Santos Pereira, Silvia Helena Barem Rabenhorst, Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Ceará 60430-270, Brazil.

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.
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http://dx.doi.org/10.3748/wjg.v21.i37.10563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588078PMC
October 2015

Characterization of Gastric Cardia Tumors: Differences in Helicobacter pylori Strains and Genetic Polymorphisms.

Dig Dis Sci 2015 Sep 24;60(9):2712-7. Epub 2015 Apr 24.

Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Street Coronel Nunes de Melo, 1315 - Rodolfo Teófilo, Fortaleza, Ceará, 60430-270, Brazil,

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.
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http://dx.doi.org/10.1007/s10620-015-3666-0DOI Listing
September 2015

A new look at osteomyelitis development--focus on CCR5delta32. Study in patients from Northeast Brazil.

Infect Genet Evol 2015 Apr 28;31:61-3. Epub 2015 Jan 28.

Universidade Federal do Ceará, Fortaleza, Ceará, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.meegid.2015.01.012DOI Listing
April 2015

Interleukin-10 gene polymorphism (-1082G/A) and allergy to efavirenz in patients infected with human immunodeficiency virus.

Braz J Infect Dis 2014 Jul-Aug;18(4):445-8. Epub 2014 May 10.

Department of Clinical Analysis and Toxicology, Faculty of Pharmacy, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.

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.
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http://dx.doi.org/10.1016/j.bjid.2014.01.009DOI Listing
October 2014

Association of TP53 codon 72 and intron 3 16-bp Ins/Del polymorphisms with cervical cancer risk.

Tumour Biol 2014 Aug 30;35(8):7435-40. Epub 2014 Apr 30.

Department of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.

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.
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http://dx.doi.org/10.1007/s13277-014-1988-8DOI Listing
August 2014

Anti-PGL1 salivary IgA/IgM, serum IgG/IgM, and nasal Mycobacterium leprae DNA in individuals with household contact with leprosy.

Int J Infect Dis 2013 Nov 16;17(11):e1005-10. Epub 2013 Jul 16.

Department of Clinical Analysis and Toxicology, Faculty of Pharmacy, Universidade Federal do Ceará, Rua Capitão Francisco Pedro, 1210, CEP 60430-370 Fortaleza, Ceará, Brazil.

Objectives: Leprosy household contacts represent a group at high risk of developing the disease. The aim of this study was to detect Mycobacterium leprae subclinical infection in this group through serological and molecular parameters.

Methods: Serum anti-PGL1 IgG/IgM and salivary anti-PGL1 IgA/IgM was investigated using an ELISA, and nasal carriage of M. leprae DNA was detected by PCR, in leprosy household contacts of paucibacillary (PB) and multibacillary (MB) household leprosy patients (n=135), their index cases (n=30), and in persons living in a low endemic city (n=17).

Results: Salivary anti-PGL1 IgA and IgM and serum anti-PGL1 IgG showed good correlation comparing contacts and index cases (p<0.01, p<0.005, and p<0.0001, respectively). This was not observed for serum anti-PGL1 IgM (p>0.05). A high frequency of anti-PGL1 IgM positivity was found in IgG-negative samples (p<0.0001). For IgG-positive samples, IgM antibodies were also positive in most of the samples. None of the 17 volunteers living in a low endemic city presented seropositivity for IgG; however, two of them showed positivity for anti-PGL1 IgM. M. leprae DNA was found in the nasal swabs of nine out of the 85 MB household leprosy contacts (10.6%) and in three out of the 50 PB household leprosy contacts (6.0%).

Conclusion: We strongly suggest that serum IgG/IgM and salivary anti-PGL1 IgA/IgM measurements are used to follow leprosy household contacts.
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http://dx.doi.org/10.1016/j.ijid.2013.05.011DOI Listing
November 2013

CDKN2A promoter hypermethylation in astrocytomas is associated with age and sex.

Int J Surg 2013 27;11(7):549-53. Epub 2013 May 27.

Universidade Federal do Ceará, Department of Pathology and Forensic Medicine, Rua Alexandre Baraúna, 949, Porangabussu, CEP 60183-630 Fortaleza, Brazil.

CDKN2A promoter hypermethylation has been widely related to many cancers. In astrocytomas, although CDKN2A (p16(INK4A) protein) is often inactivated, there are still some controversial issues regarding the mechanism by which this alteration occurs. Thus, we analyzed a series of astrocytomas to assess the association between CDKN2A expression and methylation of grade I-IV tumors (WHO) and clinicopathological parameters. DNA extracted from formalin-fixed paraffin-embedded material of 93 astrocytic tumors was available for CDKN2A promoter methylation analysis and p16(INK4A) expression by methylation-specific PCR and immunohistochemistry, respectively. A strong negative correlation between nuclear and cytoplasmic immunostaining and CDKN2A promoter methylation was found. Additionally, a significant negative correlation between CDKN2A promoter methylation and age was observed; also, female patients had statistically more CDKN2A methylated promoters (p = 0.036) than men. In conclusion, CDKN2A inactivation by promoter methylation is a frequent event in astrocytomas and it is related to the age and sex of patients.
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http://dx.doi.org/10.1016/j.ijsu.2013.05.030DOI Listing
May 2014

Interleukin polymorphisms and differential methylation status in gastric cancer: an association with Helicobacter pylori infection.

Epigenomics 2013 Apr;5(2):167-75

Universidade Federal do Ceará, Department of Pathology & Forensic Medicine, Rua Alexandre Baraúna, 949, Porangabussu, CEP 60183-630, Fortaleza, Brazil.

Aim: Interleukin polymorphisms and Helicobacter pylori infection are believed to play critical roles in DNA methylation, a process frequently associated with carcinogenesis. The aim of this study was to determine the associations between interleukin polymorphisms and methylation status of three genes related to gastric cancer. Furthermore, the influence of the H. pylori strains was evaluated.

Materials & Methods: 75 gastric tumor samples had the DNA extracted for interleukin polymorphisms genotyping by PCR-RFLP, promoter methylation by MS-PCR and detection and subtyping of H. pylori by PCR.

Results: In the cardia tumors, methylation in the COX-2 promoter was associated with IL1RN*2 (p = 0.015), and the associated genotypes IL1B511T + IL1RN*2 seem to be important in the methylation of COX-2 (p = 0.013), especially in the presence of cagA(+) (p = 0.026) and vacAs1 (p = 0.025) H. pylori strains. The associated genotypes IL6 CC+TNF GG seem to be involved in the unmethylation of CDKN2A (p = 0.046), along with H. pylori cagA(+) infection.

Conclusion: DNA methylation in gastric cancer seems to be influenced by the presence of interleukin polymorphisms and by the H. pylori cagA/vacAs1m1 strains.
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http://dx.doi.org/10.2217/epi.13.7DOI Listing
April 2013

Central giant cell lesion of the jaws: study of CCND1 gene amplification and p16INK4a protein levels.

J Mol Histol 2013 Oct 16;44(5):527-34. Epub 2013 Mar 16.

Department of Dental Clinic, Discipline of Oral and Maxillofacial Surgery and Stomatology, Federal University of Ceara School of Dentistry, Fortaleza, Brazil.

Central giant cell lesions (CGCLs) are uncommon benign jaw lesions with uncertain etiology and a variable clinical behavior. In neoplasms, alterations in molecules involved in the G1/S checkpoint are frequently found. Loss of p16(INK4a) expression or overexpression of cyclin D1 may stimulate cell proliferation. The purpose of this study was to analyze CCND1 gene amplification and the expression of p16(INK4a) in CGCLs. Structural analysis of the CCND1 was performed using chromogenic in situ hybridization. Immmunohistochemistry was used to identify p16(INK4a) protein levels. Statistical analysis correlated the two biomarkers with clinical behavior and between each other. Twenty-four lesions were included, being 11 aggressive and 13 non-aggressive. Moderate/high-level CCND1 amplification was found in 12 lesions. Also, immunoreactivity for p16(INK4a) was present in 12 cases, mainly in mononuclear cells. There was a significantly higher level of p16(INK4a) expression in mononuclear cells of non-aggressive lesions and lesions with moderate/high-level CCND1 amplification in mononuclear cells. It could be speculated that some CGCLs may develop as a true benign neoplasm. The higher expression of p16(INK4a) in non-aggressive lesions and in cases with moderate/high-level CCND1 amplification may show that these molecules have a role in CGCLs.
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http://dx.doi.org/10.1007/s10735-013-9494-7DOI Listing
October 2013

Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil.

Anticancer Res 2012 Nov;32(11):4805-11

Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.

Polymorphisms in genes encoding enzymes of folate metabolism are a focus of breast cancer risk studies due of the role of these enzymes in DNA methylation, synthesis, and repair. MTHFR, encoding for 5,10-methylenetetrahydrofolate reductase, is one of the most studied genes in this regard, but findings are controversial, and the majority of studies have analyzed polymorphisms individually. In this case control study, we examined the combination of the polymorphisms MTHFR C677T and A1298C with MTR A2756G, where MTR, methionine synthase, is an important enzyme of the folate cycle in the methylation pathway. One hundred and forty-two patients with breast cancer and controls were included and the genotypes were determined using PCR-RFLP. In the population studied, individuals carrying the polymorphic allele in the heterozygous state for both enzymes, MTHFR C677T and MTR A2756G, had an increased risk [odds ratio, OR=2.77 (95% confidence interval, CI=1.19-6.52)] for disease, compared to those with the wild genotype. In addition, individuals carrying the MTR 2756 genotype AG had an increased risk when this was combined with the MTHFR 1298 genotype CC [OR=5.13 (95% CI=0.87-38.82)]. No significant results were found from the analyses associating the MTHFR C677T and A1298C genotypes. However, when stratifying the patients by age (50 years old as the cut-off), patients over 50 years old had greater risk, with the presence of both MTHFR polymorphisms in the heterozygous state [OR=5.33 (95% CI=1.42-21.03)]. This study points out the importance of the interactions between the MTHFR C677T, MTHFR A1298C and MTR A2756G polymorphisms, and also highlights the relevance of the MTR A2756G polymorphism and age in breast cancer risk.
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November 2012

Angiogenesis inhibition by green propolis and the angiogenic effect of L-lysine on bladder cancer in rats.

Acta Cir Bras 2012 Aug;27(8):529-36

Department of Pathology, UFC, Ceara, Brazil.

Purpose: To determine the effects of water-soluble derivative of green propolis in bladder cancer angiogenesis in rats given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN).

Methods: Nine groups were established, where six of them (Groups 1 to 6), the animals received 0.05% BBN in their drinking water for 14 weeks. From the 32nd to the 40th week, Groups 1, 2, 3 and 4 were treated respectively with water, L-lysine (300 mg/kg/day), celecoxib (30 mg/kg/day) and propolis (300 mg/kg/day). Groups 5 and 6 were given propolis and L-lysine from the 1st to the 40th week (150 mg/kg/day). Microvascular density was determined by histological sections stained for the marker CD-31 and analyzed with specific software.

Results: The microvascular density in bladder carcinomas was lower (p<0.01) in rats receiving propolis than in controls given carcinogen only. On the other hand, the microvascular density of tumors in rats receiving carcinogen and L-lysine for 40 weeks from the beginning of carcinogen treatment was significantly higher (p<0.01) than in the corresponding controls.

Conclusion: Water-soluble derivative of propolis inhibits angiogenesis in BBN-induced rat bladder cancer, while L-lysine treatment stimulates angiogenesis if initiated concurrently with BBN.
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http://dx.doi.org/10.1590/s0102-86502012000800003DOI Listing
August 2012

hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions.

BMC Gastroenterol 2012 Jul 6;12:85. Epub 2012 Jul 6.

Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.

Background: Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions.

Methods: We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. The number of TP53 gene copies was investigated in gastric diseases by quantitative PCR.

Results: We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. The immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens.

Conclusions: We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation.
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http://dx.doi.org/10.1186/1471-230X-12-85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482568PMC
July 2012

TP53 codon 72 and intron 3 polymorphisms and mutational status in gastric cancer: an association with tumor onset and prognosis.

Pathobiology 2012 9;79(6):323-8. Epub 2012 Jun 9.

Section of Genetics, Department of Pathology and Forensic Medicine, Universidade Federal do Ceará, Fortaleza, Brazil.

Although TP53 alterations have been studied in human tumors, data considering the role of two common TP53 polymorphisms (Pro72Arg in codon 72 and Ins16bp in intron 3) and their associations with TP53 mutations in gastric cancer are very limited. Thus, we analyzed these parameters taking into consideration the clinicopathological data. DNA from 106 gastric tumor samples was available for TP53 Pro72Arg and TP53 Ins16bp polymorphism genotyping by PCR-RFLP and PCR, respectively. The mutational status of the TP53 exons 5-7 was assessed by the single-strand conformational polymorphism test. The TP53 72ArgArg genotype was statistically associated with patients aged ≥65 years (p = 0.039), and the intron 3 A2A2 genotype was correlated with late-stage tumors (III and IV; p = 0.043). Considering both polymorphisms, a negative correlation between the TP53 Pro-A1 haplotype and age <65 years (r = -0.211; p = 0.030) was found. Taking into account the TP53 mutations, the Pro/Pro genotype was positively correlated with the presence of exon 7 mutations (p = 0.049), and a correlation between this genotype and the number of mutations in TP53 was observed (p = 0.019). This study corroborates the understanding of TP53 polymorphisms in gastric carcinogenesis, especially regarding the genetic features in tumor onset and prognosis.
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http://dx.doi.org/10.1159/000338436DOI Listing
December 2012

Helicobacter pylori genotype and polymorphisms in DNA repair enzymes: where do they correlate in gastric cancer?

J Surg Oncol 2012 Sep 28;106(4):448-55. Epub 2012 Feb 28.

Departamento de Patologia e Medicina Legal, Universidade Federal do Ceará, Fortaleza, Brazil.

Background And Objectives: One of the mechanisms proposed by which H. pylori causes gastric cancer (GC) is through DNA damage due to chronic inflammation. Genomic integrity is guaranteed by repair enzymes such as APE-1, OGG-1, and PARP-1. Host genetic polymorphisms associated with the bacterial strain may influence the ability to repair the damage, contributing to the development of H. pylori-associated GC. The aim of this study was to determine the association of the polymorphisms APE-1 (T2197G), OGG-1 (C1245G), and PARP-1 (A40676G) with H. pylori-genotype in 109 patients with GC.

Methods: Polymorphism was assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and H. pylori detection/genotyping by PCR.

Results: In the intestinal subtype, PARP-1 wild-type was more frequent (P=0.001) in patients >50 years old. The repair enzymes genotypes analyzed in combination showed that the less pathogenic strains are associated with the APE-1 polymorphic allele and, unexpectedly, with PARP-1 wild-type, but this last one associated with APE-1 polymorphic allele or in older patients.

Conclusions: Our results indicate the importance of H. pylori and APE-1 genotypes in the gastric carcinogenesis. Also, support the hypothesis of a decrease of PARP-1 wild-type activity in older individuals. Taken together these data may be an important clue to understand the role of low-virulence strains of H. pylori in gastric carcinogenesis and point the importance to analyze the polymorphisms as a group.
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http://dx.doi.org/10.1002/jso.23077DOI Listing
September 2012

Epstein-Barr virus-associated gastric carcinoma in Brazil: comparison between in situ hybridization and polymerase chain reaction detection.

Braz J Microbiol 2012 Jan 1;43(1):393-404. Epub 2012 Jun 1.

Setor de Microbiologia, Departamento de Patologia e Medicina Legal, Universidade Federal do Ceará , Fortaleza, CE , Brasil.

Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. On the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.
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http://dx.doi.org/10.1590/S1517-838220120001000048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769002PMC
January 2012

Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent.

Mol Biol Rep 2012 Apr 2;39(4):4899-907. Epub 2011 Dec 2.

Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo, 1315, Rodolfo Teófilo, Fortaleza, CE, CEP 60430-270, Brazil.

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case-control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5'-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.
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http://dx.doi.org/10.1007/s11033-011-1285-1DOI Listing
April 2012

Cyclooxygenase-2 expression in central giant cell lesion of the jaws: an immunohistochemical study.

J Mol Histol 2012 Feb 1;43(1):59-62. Epub 2011 Nov 1.

Department of Dental Clinic, Discipline of Oral and Maxillofacial Surgery and Stomatology, Federal University of Ceará School of Dentistry, Dom Luiz 1200, Torre I, Sala 410, Aldeota, Fortaleza, Ceará, Brazil.

Central Giant Cell Lesion (CGCL) is an uncommon benign jaw lesion, with uncertain etiology, and a variable clinical behavior. Studies of molecular markers of CGCL, may help understanding better the nature and behavior of this lesion, and eventually may represent a definitive target to pharmacological approach in the treatment of CGCL. Chronic inflammation has been found to mediate a wide variety of diseases including neoplasms. Among the gene products involved in the induction of the inflammatory process, Cyclooxygenase 2 (COX-2) has been shown to have a close relationship with tumorigenesis, however COX-2 expression has never been evaluated in CGCL. The aim of the study was to investigate the expression of COX-2 in CGCL. Immunohistochemical assessment for COX-2 expression was performed in 18 patients previously diagnosed with CGCL. Multinucleated giant cells (MGC) and mononucleated stromal cells (MSC) were used in the slide analysis. Among the patients studied, 10 were male and 8 were female, with a median age of 15.4 years. Lesions in the mandible were observed in 11 cases and 7 were found in the maxilla. There were 9 aggressive and 9 non-aggressive CGCLs. COX-2 immunopositivity was present in only 3 cases stained in both MGC and MSC. All 3 cases presented with ulcerations in the mucosa lesion, suggesting that the COX-2 expression is due to the presence of inflammation. This study does not support the involvement of COX-2 in the etiophatogenesis of CGCL.
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http://dx.doi.org/10.1007/s10735-011-9369-8DOI Listing
February 2012