F. Carneiro - Academia.edu (original) (raw)

Papers by F. Carneiro

Inflammatory Bowel Diseases, 2005

Background: NOD2/CARD15 was described as the first susceptibility gene to Crohn's disease (CD). P... more Background: NOD2/CARD15 was described as the first susceptibility gene to Crohn's disease (CD). Polymorphisms in the TNFA gene and in the IL1 gene cluster, which are associated with an enhanced chronic inflammatory response, may also play a role in the development of CD. The aim of this study was to determine the association of polymorphisms in the CARD15, TNFA, IL1B, and IL1RN genes with risk of development of CD and with the clinicopathological profile of CD patients.

Virchows Archiv, 2014

Inflammatory fibroid polyps are rare mesenchymal lesions. The frequency of Helicobacter pylori in... more Inflammatory fibroid polyps are rare mesenchymal lesions. The frequency of Helicobacter pylori infection in the gastric mucosa overlying inflammatory fibroid polyps and its relation with the histologic features of the polyps are undetermined. The clinico-pathological features of inflammatory fibroid polyps, the frequency of Helicobacter pylori infection in the overlying gastric mucosa, and its putative impact on the phenotype of the polyps were evaluated. Gastric inflammatory fibroid polyps diagnosed in our Hospital from 1998 to 2012 were reviewed and the histological. The histological sections were stained with hematoxylin and eosin and modified Giemsa for the evaluation of Helicobacter pylori infection. Inconclusive cases were further analyzed by immunohistochemistry with anti-Helicobacter pylori antibody. Diagnosis was confirmed in 54 polyps, 85 % developed in females, mean age 63±11 years. Most polyps were sessile (74 %), with a mean size of 15±12 mm, 96 % were located in the antrum and 85 % were removed by snare polypectomy. Helicobacter pylori infection was identified in 48 % of the polyps. Most inflammatory fibroid polyps developed in the submucosa, and mucosal extension was observed in 96 % of the cases. Chronic gastritis was observed in all cases (63 % with activity, 31 % with intestinal metaplasia, and 61 % with foveolar hyperplasia). Erosion and ulceration of the overlying gastric mucosa was observed in 48 % and 11 % of the polyps, respectively. Onion skin features were present in 52 % of the polyps and were more frequently observed in cases without evidence of Helicobacter pylori infection. Background changes in gastric mucosa were not distinctive according to Helicobacter pylori infection. Chronic atrophic gastritis with intestinal metaplasia was associated with the presence of perivascular onion skin lesions. To our knowledge, this is the second largest series of gastric inflammatory fibroid polyps. Helicobacter pylori infection was identified in about half of the cases and was associated with a lower frequency of onion skin features in the polyps.

European Journal of Cancer, 2014

splicing products of the ING1 gene affect apoptosis and cell senescence, but the mechanisms are c... more splicing products of the ING1 gene affect apoptosis and cell senescence, but the mechanisms are currently unclear. Materials and Methods: Primary diploid fibroblasts were examined for their propensity to express different isoforms of ING1, and their response to increased and decreased levels of ING1 was examined. Results: Expression of the alternatively spliced ING1a tumor suppressor increases >10-fold during replicative senescence. ING1a overexpression inhibits growth; induces a large flattened cell morphology and the expression of senescence-associated b-galactosidase; increases Rb, p16, and cyclin D1 levels; and results in the accumulation of senescence-associated heterochromatic foci. Here we identify ING1a-regulated genes and find that ING1a induces the expression of a disproportionate number of genes whose products encode proteins involved in endocytosis. Intersectin 2 (ITSN2) is most affected by ING1a, being rapidly induced >25-fold. Overexpression of ITSN2 independently induces expression of the p16 and p57 KIP2 cyclin-dependent kinase inhibitors, which act to block Rb inactivation, acting as downstream effectors of ING1a. ITSN2 is also induced in normally senescing cells, consistent with elevated levels of ING1a inducing ITSN2 as part of a normal senescence program. Inhibition of endocytosis or altering the stoichiometry of endosome components such as Rab family members similarly induces senescence. Knockdown of ITSN2 also blocks the ability of ING1a to induce a senescent phenotype, confirming that ITSN2 is a major transducer of ING1ainduced senescence signaling. Conclusions: These data identify a pathway by which ING1a induces senescence and indicate that altered endocytosis activates the Rb pathway, subsequently effecting a senescent phenotype. Since ING1a levels increase naturally near the end of cell replicative activity, the alternative splicing of ING1 might represent a regulatory event that subsequently prevents senescing cells from responding normally to mitogenic factors, helping enforce the senescence phenotype believed to block the progression of cancer.

conganat.uninet.edu

... Entre los peregrinos se destacan Carlo Magno (778 DC), el Rey Alfonso II de España (813 DC), ... more ... Entre los peregrinos se destacan Carlo Magno (778 DC), el Rey Alfonso II de España (813 DC), El Cid Campeador ... Hay cinco pasos principales de aproximadamente 3.300 pies, uno de los cuales,Cruz de Ferro supera los 5.000 pies. ... Louis, Dr. Vincenzo Eusebi, Bologna, Italia. ...

The American journal of gastroenterology, 1996

Bacterial attachment is a prerequisite for colonization of the gastric epithelial surface. Recent... more Bacterial attachment is a prerequisite for colonization of the gastric epithelial surface. Recently, it was demonstrated that the receptor for Helicobacter pylori is the blood group antigen Lewis b, which is exposed only in blood group O. We prospectively examined the prevalence of blood groups in H. pylori-positive and -negative patients. To avoid a genetic bias, we compared blood group prevalence of our patients with the general population of Israel. In the 187 consecutive patients we studied, in addition to regular upper endoscopy, H. pylori status and blood group. Exposure to H. pylori was diagnosed when the results of two or more of three methods were found to be positive. Exposure was found in 123 patients and 64 negative. The groups were similar in average age and origin, and no significant difference was demonstrated for blood group. Blood group distribution between any given origin was not significantly different in our patients and in a sample of 182,701 blood donors. Posi...

Cancer research, 1999

Intestinal metaplasia is a well-established premalignant condition of the stomach that is charact... more Intestinal metaplasia is a well-established premalignant condition of the stomach that is characterized by mucin carbohydrate modifications defined by histochemical methods. The purpose of the present study was to see whether the expression of mucin core proteins was modified in the different types of intestinal metaplasia and to evaluate the putative usefulness of mucins as "molecular markers" in this setting. We used a panel of monoclonal antibodies with well-defined specificities to MUC1, MUC2, MUC5AC, and MUC6 to characterize the expression pattern of mucins. In contrast to normal gastric mucosa, the complete form or type I intestinal metaplasia (n = 20) displayed little or no expression of MUC1, MUC5AC, or MUC6 in the metaplastic cells and strong expression of the intestinal mucin MUC2 in the goblet cells of all cases. The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in c...

Here, we evaluated a previously established peptide nucleic acid-fluorescence in situ hybridizati... more Here, we evaluated a previously established peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) method as a new diagnostic test for Helicobacter pylori clarithromycin resistance detection in paraffin-embedded gastric biopsy specimens. Both a retrospective study 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. Compared to the reference method (culture followed by Etest), the specificity and sensitivity of PNA-FISH were 90.9% (95% confidence interval [CI], 57.1% to 99.5%) and 84.2% (95% CI, 59.5% to 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 sensitivity of 80.0% (95% CI, 29.9% to 98.9%) and specificity of 93.8% (95% CI, 67.7% to 99.7%). These values likely represent underestimations, as some of the discrepant results corresponded to patients infected by more than one strain. PNA-FISH appears to be a simple, quick, and accurate method for detecting H. pylori clarithromycin resistance in paraffin-embedded biopsy specimens. It is also the only one of the methods assessed here that allows direct and specific visualization of this microorganism within the biopsy specimens, a characteristic that allowed the observation that cells of different H. pylori strains can subsist in very close proximity in the stomach.

Laboratory Investigation, 2002

It has been advanced that the trefoil factor (TFF) 1 gene is a candidate tumor-suppressor gene an... more It has been advanced that the trefoil factor (TFF) 1 gene is a candidate tumor-suppressor gene and may be involved in the development and/or progression of human gastric cancer. We aimed to clarify the putative role of TFF1 in gastric carcinogenesis. Ninety gastric carcinomas and eight gastric carcinoma-derived cell lines were screened for TFF1 mutations; subsets of the primary tumors and of the cell lines were subjected to loss of heterozygosity (LOH), immunohistochemistry, and promoter methylation analyses. TFF1 mutations were not detected in any of 90 gastric carcinomas. Eight (28%) of 28 informative cases displayed LOH at the TFF1 locus and absence of TFF1 staining by immunohistochemistry. These results indicate a frequent loss of TFF1 expression in gastric carcinomas through a mutation-independent mechanism. Extensive TFF1 promoter methylation was observed in nonexpressing gastric carcinoma-derived cell lines and tissues. Expressing cell lines, as well as normal gastric mucosa, presented little or no methylation of the promoter. Gastric carcinoma DNA presented de novo methylation of the promoter. These results point to the involvement of promoter methylation in the shutting down of TFF1. We conclude that TFF1 point mutations seem to be a rare event in gastric carcinogenesis. The loss of expression of TFF1 in a proportion of gastric carcinomas may be explained by LOH and methylation of the TFF1 promoter region. Our results further support the role of TFF1 inactivation in gastric carcinogenesis, in agreement with the results obtained in the Tff1-knockout mice model. (Lab Invest 2002,

Scandinavian Journal of Gastroenterology, 2005

We report the case of a 56-year-old woman followed for ulcerative colitis since 1987. In 1993, sh... more We report the case of a 56-year-old woman followed for ulcerative colitis since 1987. In 1993, she underwent a total hysterectomy with bilateral salpingo-oophorectomy. In 1996, a narrowing of the lumen at 20 cm of the anal margin was observed and she was put under endoscopic observation. In 1998, a mass in the stricture was observed, with significant narrowing of the lumen. Histologic examination revealed a biphasic tumor with features of malignant mixed müllerian tumor. Five years after surgery and chemotherapy with paclitaxel and carboplatinum, the patient remains well.

Human Pathology, 1992

RefDoc Bienvenue - Welcome. Refdoc est un service / is powered by. ...

Virchows Archiv, 2012

For several years, the lack of consensus on definition, nomenclature, natural history, and biolog... more For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa00.557; p<0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p<0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

Virchows Archiv, 2009

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outc... more Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

Ultrastructural Pathology, 1992

The present study was undertaken to determine whether or not signet ring cell (diffuse, isolated ... more The present study was undertaken to determine whether or not signet ring cell (diffuse, isolated cell) gastric carcinomas display a specific profile at the ultrastructural, morphometric, and DNA cytometric levels. Thirty-two cases of gastric carcinoma and 8 cases of peptic ulcer (control group) were studied with electron microscopy, morphometry, flow cytometry, and image cytometry. Despite the ultrastructural cellular heterogeneity of signet ring cell carcinomas, the neoplastic cells display fairly constant morphometric features: The cellular and nuclear volumes are significantly smaller than those of the other types of gastric carcinomas and closely resemble those of normal foveolar cells. The relatively small size of signet ring cell carcinoma nuclei fits with the high percentage of the cases of this type of gastric carcinoma that are either diploid or nearly diploid. There is a relationship between the infiltrative pattern of growth of gastric carcinoma (regardless of histologic subtype and ultrastructural cell differentiation) and the small size of neoplastic cells and their nuclei.

Trends in Molecular Medicine, 2013

Gastric cancer: epidemiology, clinicopathological features, and clinical management GC represents... more Gastric cancer: epidemiology, clinicopathological features, and clinical management GC represents a high burden in terms of incidence and cancer-related mortality, being the fourth most common malignancy in the world and the second leading cause of

Transplantation Proceedings, 2000

Seminars in Diagnostic Pathology, 2008

The overall survival of gastric cancer patients remains poor despite efforts and advances in its ... more The overall survival of gastric cancer patients remains poor despite efforts and advances in its prevention, diagnosis, and treatment. The development of new therapies is crucial for the effective control of this disease. An increasing number of genetic and epigenetic alterations have been associated with distinct histological types of gastric cancer. In this review, we will discuss the involvement of E-cadherin, EGFR, ERBB2, MMR genes, KRAS, and PIK3CA in the development and progression of gastric cancer and their role as biomarkers or as novel putative targets for therapy.

Scandinavian Journal of Gastroenterology, 2007

Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trend... more Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trends and etiological factors. However, the available information is not always collected in population cancer registries, and heterogeneous criteria have been applied for the histopathological classification of tumors. We describe the pathological features of incident gastric and esophageal cancers identified within the European Prospective Investigation into Cancer and Nutrition (EPIC). In an investigation on gastric and esophageal cancer (EUR-GAST) in the EPIC project, a validation study of diagnoses reported by EPIC centers was conducted by a European panel of pathologists. Original pathology reports, stained slides of tumors and the respective paraffin blocks were requested from the centers. The whole series encompassed 467 cancer cases (gastric and esophageal cancers). Material was available for histopathological validation in 263 cases (56%); in the remaining cases, information was retrieved from the original reports (n=110; 24%) or codes provided by the EPIC centers (n=94; 20%). Among cases submitted to histopathological validation reported originally as unknown histotype or unknown site, a specific diagnosis was made in 95% and 74% of the cases, respectively. In cases for which only the original reports were available, the respective percentages were 46% and 67%. Gastric adenocarcinomas were classified according to site (cardia (29.4%), non-cardia (48.2%) and unknown (22.4%)) and histological type (intestinal (33.4%), diffuse (33.7%) and mixed, unclassified or unknown (32.9%)). Frequency of cardia was higher in Northern countries (35%) than in Mediterranean countries (18%). In addition to providing epidemiological data within the EPIC cohort on gastric and esophageal adenocarcinomas, the results reported here confirm the relevance of a validation study, notably for multicenter studies.

Pediatric Surgery International, 1998

Pathology - Research and Practice, 1995

Pathology - Research and Practice, 1999

Among 474 cases of gastric carcinoma studied in gastrectomy specimens from 1990 to 1996, only one... more Among 474 cases of gastric carcinoma studied in gastrectomy specimens from 1990 to 1996, only one (0.21 %) showed positivity for vimentin. It was located on a gastric stump and, endoscopically, the tumor was classified as early gastric carcinoma type IIb + IIc. Histologically, tumor cells were extensively round to polygonal and had eosinophilic, or clear cytoplasm; the nuclei were large with conspicuous nucleoli. In some arcas, the cytoplasm showed vimentin and(or cytokeratin coexpression by double immunostaining. Our results and the patient's rapid deterioration (death occurred six months after surgery) suggest that this type of tumor, although diagnosed as early carcinoma, behaved like an advanced malignancy.