Rui M Ferreira

University of Nottingham, Nottigham, England, United Kingdom

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Publications (16)87.71 Total impact

  • Virchows Archiv. A, Pathological anatomy and histopathology 07/2013; 2013 Jul 26. [Epub ahead of print].
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    ABSTRACT: First-degree relatives (FDR) of early-onset gastric cancer (EOGC) is presumed to be a population with a distinct molecular and phenotypic profile, regarding the prevalence of gastric premalignant conditions and the association with Helicobacter pylori infection and host proinflammatory gene polymorphisms. A case-control study was conducted with FDR of EOGC patients (n = 103) and age and gender matched controls (n = 101; ranging from spouses to neighbors and dyspeptics). Upper endoscopy was performed, Operative Link on Gastritis Assessment (OLGA) system used for staging and H. pylori (cagA and vacA) and host IL1B-511, IL1RN intron2 VNTR and IFNGR1-56 genotyping. Seventy percent of cases showed atrophy, while 19 % presented with high-stage gastritis (OLGA stage III or IV) (p < 0.001); gastric dysplasia was present in seven cases (vs none in controls) (p = 0.007). In cases, H. pylori was present in 82 % (vs 62 % in controls; p = 0.004) with vacA s1 and vacA m1 + strains significantly associated with the presence of atrophy; individuals homozygous for IL1B-511*T present a significantly higher risk for dysplasia. An increased global prevalence of IFNGR1-56*T/*T polymorphism (37 % in cases vs 24 % in controls; p = 0.03) was observed with no association with atrophic changes or dysplasia. All trends observed were kept when comparing FDR of EOGC with spouses, neighbors, or dyspeptic controls. We demonstrated that FDR of EOGC patients have an increased prevalence of high-risk OLGA stages and dysplasia that seem to be associated with high virulence H. pylori strains and pro-inflammatory host genotypes, including a possible population-specific risk marker. FDR of EOGC patients may merit specific management through endoscopic and histopathological adequate assessment of gastric mucosa and surveillance.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2013; · 2.68 Impact Factor
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    ABSTRACT: In here, we evaluated a previously established PNA-FISH method as a new diagnostic test for H. pylori clarithromycin resistance detection in paraffin embedded gastric biopsies. Both a retrospective and a prospective cohort study were conducted to evaluate the specificity and sensitivity of a PNA-FISH method to determine H. pylori clarithromycin resistance. In the retrospective study (n=30 patients), full agreement between PNA-FISH and PCR-sequencing was observed. When compared to the reference method (culture followed by Etest®), specificity and sensitivity of PNA-FISH were 90.9% (95% confidence interval [CI], 57.1-99.5%) and 84.2% (95% CI, 59.5-95.8%), respectively. In the prospective cohort (n=93 patients), 21 cases were positive by culture. For the patients harboring clarithromycin-resistant H. pylori, the method showed a sensitivity of 80.0% (95% CI, 29.9-98.9%) and specificity of 93.8% (95% CI, 67.7-99.7%). These values are likely to be underestimated, as in some discrepant results patients were infected by more than one strain. PNA-FISH appears to be a simple, quick and an accurate method for detecting H. pylori clarithromycin resistance in paraffin embedded biopsies. It is also the only one of the methods assessed here that allows direct and specific visualization of this microorganism within the biopsies, a characteristic that allowed observing that different H. pylori strains can subsist very closely in the stomach.
    Journal of clinical microbiology 04/2013; · 4.16 Impact Factor
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    ABSTRACT: The present report describes a novel method for genotyping the virulence-associated vacA intermediate (i) region of Helicobacter pylori in archive material.vacA i-region genotypes as determined by the novel method, were completely concordant with those of sequence analysis and with those of functional vacuolation activity. The method was further validated directly in gastric biopsy specimens of 386 H. pylori-positive cases, and effective characterization of the vacA i-region was obtained in 191 of 192 (99.5%) frozen and in 186 of 194 (95.9%) formalin-fixed paraffin-embedded gastric biopsy specimens, respectively.The genotyping method was next used to address the relationship between the vacA genotypes and the cagA status. The vacA i1 genotype was associated with vacA s1, vacA m1 and cagA-positive genotypes (P < 0.0001), while the vacA i2 genotype was closely related with vacA s2, vacA m2 and cagA-negative genotypes (P < 0.0001).The relationship between H. pylori vacA i-region genotypes and gastric disease development was subsequently evaluated in the Portuguese population. Patients infected with vacA i1 strains showed an increased risk for gastric atrophy and for gastric carcinoma with odds ratio of 8.0 (95%, CI 2.3-27) and of 22 (95%, CI 7.9-63), respectively.Taken together, the results show that this novel H. pylori vacA i-region genotyping method can be applied directly to archive material, providing a fast evaluation of strain virulence determinants without the need of culture. The results further emphasize that the characterization of the vacA i-region may be useful to identify patients at higher risk of gastric carcinoma development.
    Journal of clinical microbiology 10/2012; · 4.16 Impact Factor
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    ABSTRACT: First-degree relatives (FDRs) of early-onset gastric carcinoma (EOGC) patients are at increased risk of cancer development. OLGA/OLGIM (Operative Link on Gastritis/Intestinal Metaplasia Assessment) classifications have been proposed for the identification of individuals at high risk of gastric cancer development. To estimate the prevalence and severity of premalignant conditions and lesions in FDRs of EOGC patients. A case-control study was conducted encompassing 103 FDRs of EOGC patients (cases) and 101 age- and gender-matched controls, all submitted to upper GI endoscopy and OLGA and OLGIM used for staging as well as modified versions with exclusion of the biopsies from incisura angularis in the analysis. Helicobacter pylori infection was present in 82% of cases (P = 0.001). Atrophy was present in 70% of cases (OLGA stages I-IV). High-risk stages (III-IV) were identified only in cases (19%) (P < 0.001). Dysplasia was diagnosed only in cases (n = 7, P = 0.007). The application of OLGIM, modified OLGA and modified OLGIM classifications led to downgrade of stages in comparison with the original OLGA classification (27%, 15% and 30% respectively). In all classification systems, dysplastic lesions clustered (86%) in high-risk stages. FDRs of EOGC patients have, even at young ages, a high prevalence of H. pylori infection, high-risk OLGA and OLGIM stages and dysplasia. These patients should undergo accurate endoscopic observation with at least four biopsies in antrum and corpus to allow adequate staging and follow-up of premalignant conditions and lesions scored in high-risk stages, in accordance with international guidelines recently proposed.
    Alimentary Pharmacology & Therapeutics 05/2012; 35(12):1451-9. · 4.55 Impact Factor
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    ABSTRACT: As CDX2 expression precedes the occurrence of gastric preneoplastic lesions in the intestinal differentiation pathway, study of these steps of gastric carcinogenesis may contribute toward understanding the early effects of gastric cancer determinants. Our aim was to quantify the association between Helicobacter pylori infection and other environmental factors and the gastric expression of CDX2. Dyspeptic patients undergoing an upper digestive endoscopy (Gastroenterology Department, Maputo Central Hospital) were consecutively invited to participate in this study and classified as having normal stomach/chronic nonatrophic gastritis (NS/CNAG), chronic atrophic gastritis (CAG), or intestinal metaplasia (IM). For all patients with CAG or IM and a subsample of NS/CNAG patients (sex-matched and age-matched, 1 : 2), H. pylori infection and CDX2 gene expression were assessed by histology and PCR and by immunohistochemistry, respectively. Age-adjusted, sex-adjusted, education-adjusted, and H. pylori infection-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were computed. CDX2 expression was observed in 56 NS/CNAG (49.1%), 39 CAG (86.7%), and all IM patients (n=12). It was more frequent among the H. pylori-infected patients (OR=2.26, 95% CI: 1.00-5.15). Infection with high-virulence strains was associated with CDX2 expression in patients with CAG (cagA, OR=3.20, 95% CI: 1.35-7.52) and IM (vacA m1, OR=5.86, 95% CI: 1.08-31.62). Patients with a lower frequency of vegetable consumption had a higher risk of marked CDX2 expression (OR=3.64, 95% CI: 1.02-12.95). The virulence of the infecting strains and vegetable consumption were associated with CDX2 expression and may play a role in the progression to more advanced lesions.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2012; 21(6):532-540. · 2.21 Impact Factor
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    ABSTRACT: To characterize the variation in virulence of Helicobacter pylori associated with CagA Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs, and to explore its relationship with the histopathological features of chronic gastritis and with the development of gastric carcinoma. A total of 169 H. pylori-infected patients with chronic gastritis and gastric carcinoma were studied. The presence of cagA and the number and type of EPIYA motifs were determined by polymerase chain reaction. Infection with strains harbouring two or more CagA EPIYA C motifs was associated with the presence of surface epithelial damage, and with atrophic gastritis and gastric carcinoma. The magnitude of risk for atrophic gastritis and gastric carcinoma increased with increasing number of EPIYA C motifs: strains with one EPIYA C motif conferred a risk (odds ratio [OR]) of 7.3 [95% confidence interval (CI) 2.1-25] for atrophic gastritis, whereas strains with two or more EPIYA C motifs conferred a risk (OR) of 12 (95% CI 2.5-58); strains with one EPIYA C motif conferred a risk (OR) of 17 (95% CI 5.4-55) for gastric carcinoma, whereas strains with two or more EPIYA C motifs conferred a risk (OR) of 51 (95% CI 13-198). Characterization of the number of H. pylori EPIYA C motifs is important in better defining gastric carcinoma risk.
    Histopathology 02/2012; 60(6):992-8. · 2.86 Impact Factor
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    ABSTRACT: H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.
    PLoS ONE 01/2012; 7(4):e35072. · 3.73 Impact Factor
  • The American Journal of Gastroenterology 01/2012; 107(1):145-6. · 7.55 Impact Factor
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    ABSTRACT: There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions. This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression. The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains. H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.
    The American Journal of Gastroenterology 02/2011; 106(5):867-74. · 7.55 Impact Factor
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    ABSTRACT: Triple therapy is the gold standard treatment for Helicobacter pylori eradication from the human stomach, but increased resistance to clarithromycin became the main factor of treatment failure. Until now, fastidious culturing methods are generally the method of choice to assess resistance status. In this study, a new genotypic method to detect clarithromycin resistance in clinical samples, based on fluorescent in situ hybridization (FISH) using a set of peptide nucleic acid probes (PNA), is proposed. The set of probes targeting the point mutations responsible for clarithromycin resistance was applied to H. pylori suspensions and showed 100% sensitivity and specificity (95% CI, 79.9-100 and 95% CI, 71.6-100 respectively). This method can also be amenable for application to gastric biopsy samples, as resistance to clarithromycin was also detected when histological slides were tested. The optimized PNA-FISH based diagnostic method to detect H. pylori clarithromycin resistance shown to be a very sensitive and specific method for the detection of clarithromycin resistance in the H. pylori smears and also proved to be a reliable method for the diagnosis of this pathogen in clinical samples and an alternative to existing plating methods.
    BMC Microbiology 01/2011; 11:101. · 3.10 Impact Factor
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    ABSTRACT: The transmission of the gastric pathogen Helicobacter pylori involves the oral route. Molecular techniques have allowed the detection of H. pylori DNA in samples of the oral cavity, although culture of H. pylori from these type of samples has been sporadic. Studies have tried to demonstrate the presence of H. pylori in adenotonsillar tissue, with contradictory results. Our aim was to clarify whether the adenotonsillar tissue may constitute an extra gastric reservoir for H. pylori. Sixty-two children proposed for adenoidectomy or tonsillectomy were enrolled. A total of 101 surgical specimens, 55 adenoid and 46 tonsils, were obtained. Patients were characterized for the presence of anti-H. pylori antibodies by serology. On each surgical sample rapid urease test, immunohistochemistry, fluorescence in situ hybridization (FISH) with a peptide nucleic acid probe for H. pylori, and polymerase chain reaction-DNA hybridization assay (PCR-DEIA) directed to the vacA gene of H. pylori were performed. Thirty-nine percent of the individuals had anti-H. pylori antibodies. Rapid urease test was positive in samples of three patients, all with positive serology. Immunohistochemistry was positive in samples of two patients, all with negative serology. All rapid urease test or immunohistochemistry positive cases were negative by FISH. All samples tested were negative when PCR-DEIA for H. pylori detection was used directly in adenotonsillar specimens. The adenotonsillar tissue does not constitute an extra gastric reservoir for H. pylori infection, at least a permanent one, in this population of children. Moreover, techniques currently used for detecting gastric H. pylori colonization are not adequate to evaluate infection of the adenotonsillar tissues.
    International journal of pediatric otorhinolaryngology 05/2010; 74(7):807-11. · 0.85 Impact Factor
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    ABSTRACT: Helicobacter pylori induces an invasive phenotype in gastric epithelial cells through a mechanism that requires the type IV secretion system and the phosphorylation of c-Met. The E-cadherin-catenin complex is a major component of the adherens junctions and functions as an invasion suppressor. We investigated whether E-cadherin has a role in H. pylori-induced, c-Met phosphorylation-dependent cell-invasive phenotype. AGS cells that lack E-cadherin and that are invasive to H. pylori stimulation were transduced with E-cadherin and infected with H. pylori. NCI-N87 cells, which endogenously express E-cadherin, were also used for infection experiments. E-cadherin was sufficient to suppress not only H. pylori-mediated cell-invasive phenotype but also c-Met and p120-catenin tyrosine phosphorylation. H. pylori infection led to increased interactions between E-cadherin and p120-catenin, c-Met and E-cadherin, and c-Met and p120-catenin. Using in vitro infection assays, we showed that H. pylori CagA interacts with E-cadherin, p120-catenin, and c-Met. Finally, using small interfering RNA, we showed that interactions between CagA and E-cadherin and between CagA and p120-catenin were established through c-Met. We suggest that H. pylori alters the E-cadherin-catenin complex, leading to formation of a multiproteic complex composed of CagA, c-Met, E-cadherin, and p120-catenin. This complex abrogates c-Met and p120-catenin tyrosine phosphorylation and suppresses the cell-invasive phenotype induced by H. pylori.
    The Journal of Infectious Diseases 10/2009; 200(5):745-55. · 5.85 Impact Factor
  • Gastroenterology 01/2009; 136(5). · 12.82 Impact Factor
  • Gastroenterology 01/2009; 136(5). · 12.82 Impact Factor
  • Gastroenterology 01/2008; 134(4). · 12.82 Impact Factor

Publication Stats

87 Citations
87.71 Total Impact Points

Institutions

  • 2012
    • University of Nottingham
      Nottigham, England, United Kingdom
    • Centro Hospitalar do Porto
      Oporto, Porto, Portugal
  • 2009–2012
    • University of Porto
      • Institute of Molecular Pathology and Immunology (IPATIMUP)
      Oporto, Porto, Portugal