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C N Leitao

Publications and source records attributed to C N Leitao.

7 recordsLinked to original sources
PubMed2000

Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach.

Mutation searching was performed in the hMSH2 and hMLH1 genes in 20 Portuguese families representing 124 registered affected individuals. Of the 20, 16 fulfilled the classic 'Amsterdam' criteria for HNPCC, whereas the remaining four families satisfied a modified set of criteria. These criteria required a CRC diagnosed before age 50 years and cancers diagnosed in two other relatives within the HNPCC spectrum. A multi-method approach was performed using the protein truncation test (PTT), single strand conformation polymorphism (SSCP) with two different sets of conditions, heteroduplex analysis (HA) and denaturing gradient gel electrophoresis (DGGE). Putative phenotype-genotype correlations were also explored. Ten different germline mutations were identified. Six of these were found in hMLH1 in seven families and four in hMSH2 in four families. SSCP and DGGE had the highest diagnostic yields with the percentage of variants detected above 67% and together HA and PTT had the lowest. No single technique detected all variants. Trends for the absence of extracolonic manifestations were observed in families carrying hMLH1 germline mutations (four of seven in hMLH1 vs one of four in hMSH2). Most of the families with rectal cancer were associated with hMLH1 (six of seven in hMLH1 vs two of four in hMSH2). A multi-technique approach is necessary to identify a high percentage of germline mutations. Seven novel mutations were found in this Portuguese population.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Non-goblet cell population of Barrett's esophagus: an immunohistochemical demonstration of intestinal differentiation.

Barrett's esophagus develops with the following 2 distinct types of lining mucosa: with and without specialized intestinal metaplasia (SIM). Goblet cells found only in SIM areas identify an intestinal phenotype, recognized as the histological hallmark diagnosing Barrett's metaplasia, and selecting high-risk patients for endoscopic surveillance. The columnar non-goblet cells are the major component of the heterogeneous Barrett's metaplastic cell population and are present in areas either with or without SIM. Their significance in the differentiation of columnar-lined esophagus, and their relationship to malignancy, is still unclear. This immunohistochemical study used two markers of enterocytic differentiation, to explore the intestinal phenotype of the non-goblet cell population of Barrett's epithelium and Barrett's-associated adenocarcinoma cells. Sucrase-isomaltase (SI) and dipeptidilpeptidase IV (DPP) immunoexpression was assessed in paraffin-embedded samples of 12 surgical specimens containing Barrett's esophageal mucosa in association with adenocarcinoma/high grade dysplasia. Ileal mucosa and mucosa from normal gastric and esophageal segments of the surgical specimen were used as positive and negative controls, respectively. SI and DPP were expressed by the neoplastic cells and the columnar non-goblet, being negative in goblet cells. The localization of the enzymes was predominantly apical for SI and cytoplasmatic for DPP. There was immunoreactivity for SI in 58.3% of the carcinomas and in 66.6% of Barrett's mucosa, with equal frequency in areas with and without SIM. DPP was identified in 66.6% of the carcinomas, in 50% of the cases of Barrett's metaplasia with SIM, and in 75% of those without SIM. The columnar non-goblet cell components of Barrett's metaplasia contain small intestine enzymes in the areas either with or without SIM, which suggests that they identify an "incomplete form" of intestinal metaplasia. The demonstration that the two enzymes, SI and DPP, are produced by the columnar non-goblet cell metaplastic population and by the neoplastic cells of the associated adenocarcinoma, indicates that, in addition to the goblet cells, the non-goblet elements may also be involved in the malignant transformation of Barrett's esophagus.

Adenocarcinoma↗
PubMed1994

Red wine consumption and gastric cancer in Portugal: a case-control study.

The present case-control study was designed mainly to estimate the risk of gastric cancer associated with consumption of alcoholic beverages. Seventy-four cases were selected from patients undergoing endoscopy with a histologically confirmed diagnosis of gastric cancer and matched by age and sex to a pool of controls (193) from three different sources, at the same hospital ward. After adjustment for several confounders, consumption of more than one bottle of red wine per day 20 years prior to the interview showed an odds ratio (OR) = 2.61 (P = 0.049), with a dose-response relationship increasing from 1.36 for those consuming less than one glass of wine per meal, up to 3.67 if the daily consumption exceeded one bottle of red wine. Other statistically significant determinants of the disease occurrence were low education level (OR = 4.33; P = 0.0008) and low social class (OR = 2.77; P = 0.016), as well as the regular practice of preserving food by smoke at home (OR = 1.91; P = 0.032).

Adult↗
PubMed1994

DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation.

Several studies have suggested that DNA hypomethylation is an early step in colorectal carcinogenesis. However, it is not clear at which stage in carcinogenesis this hypomethylation occurs, what promotes it, the extent to which it can be reversed and the consequences of such reversal in affecting tumour development. In an attempt to address some of these questions, we studied three groups of subjects with similar age and gender distributions: a group of 12 patients with colorectal carcinomas; a group of 12 patients with colorectal adenomas; and a group of eight healthy control subjects. Two experimental protocols were employed. In the first protocol, intrinsic DNA methylation was evaluated in neoplastic and in normal-appearing rectal mucosa of patients with colonic carcinomas or adenomas, compared with a group of healthy controls. In the second protocol, we examined, in a prospective and controlled fashion, the effect of folic acid supplementation (10 mg/day) on the degree of DNA methylation of rectal mucosa from those same patients after removal of the neoplasms. The degree of intrinsic DNA methylation was assessed on the basis of the capacity of the DNA isolates to serve as methyl acceptors in in vitro incubations that contained DNA methylase and [3H-methyl] S-adenosylmethionine. Intrinsic DNA methylation was significantly lower in carcinomas than in adenomas (P < 0.005). In addition, normal-appearing rectal mucosa from patients with carcinomas was significantly less methylated than in healthy controls (P < 0.005); the mean value found in the latter was also greater than the value observed in patients with adenomas, but not significantly so (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1993

Anti-Helicobacter pylori antibodies prevalence and gastric adenocarcinoma in Portugal: report of a case-control study.

Evidence from large cohort studies has established an increased risk of gastric cancer for individuals infected with Helicobacter pylori (HP). In low incidence countries, like the United Kingdom and Sweden, case-control studies suggested that the prevalence of anti-HP antibodies in gastric cancer patients (at the time of cancer diagnosis) is greater than in control populations. We present results from a case-control study of the prevalence of IgG anti-HP antibodies in gastric cancer patients and a control population in a country with a high incidence of gastric cancer. Sera were studied from 80 gastric cancer patients (GC group) admitted consecutively to our department in 1990/91, and from 80 controls (CT group) matched by age and sex. IgG anti-HP was determined by ELISA. Patients' files were reviewed for evidence of previous diagnosis of peptic ulcer, gastric surgery, tumor localization and histopathological classification. Controls were submitted to a questionnaire for past history of peptic ulcer and gastric surgery. Positive results for anti-HP were: gastric cancer patients, 70.0%; control group, 81.5% (NS). However, the median optical densities (OD, a measure of antibody concentration) were significantly lower in the gastric cancer group than in controls: gastric cancer patients, 0.720 +/- 0.424 OD; control group, 0.906 +/- 0.443 OD (P = 0.004). There were no differences concerning past history of peptic ulcer or surgery. The proportion of positives for cancer of the cardia (66.7%) was lower than for the other tumour localizations (70.4%) (NS). Anti-HP positivity was lower in patients with gastric cancer associated with intestinal metaplasia than in controls (P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗