P53 and Rb tumor suppressor gene alterations in gastric cancer

Inactivation of tumor suppressor genes has been frequently observed in gastric carcinogenesis. Our purpose was to study the involvement of p53, APC, DCC, and Rb genes in gastric carcinoma. METHOD: Loss of heterozygosity of the p53, APC, DCC and Rb genes was studied in 22 gastric cancer tissues using polymerase chain reaction; single-strand conformation polymorphism of the p53 gene exons 5-6 and exons 7-8 was studied using 35S-dATP, and p53 expression was detected using a histological immunoperoxidase method with an anti-p53 clone. RESULTS AND DISCUSSION: No loss of heterozygosity was observed in any of these tumor suppressor genes; homozygous deletion was detected in the Rb gene in 23% (3/13) of the cases of intestinal-type gastric carcinoma. Eighteen (81.8%) cases showed band mobility shifts in exons 5-6 and/or 7-8 of the p53 gene. The presence of the p53 protein was positive in gastric cancer cells in 14 cases (63.6%). Normal gastric mucosa showed negative staining for p53; thus, the immunoreactivity was likely to represent mutant forms. The correlation of band mobility shift and the immunoreactivity to anti-p53 was not significant (P = .90). There was no correlation of gene alterations with the disease severity. CONCLUSIONS: The inactivation of Rb and p53 genes is involved in gastric carcinogenesis in our environment. Loss of the Rb gene observed only in the intestinal-type gastric cancer should be further evaluated in association with Helicobacter pylori infection. The p53 gene was affected in both intestinal and diffuse histological types of gastric cancer.

Maladies peptiques [Acid related diseases progress in 2007].

The treatment of reflux disease did not changed. PPI treatment remains the first line treatment and surgery a second line treatment. The effect of surgery in reflux disease reduces and, after ten years, a part of the operated patients needs PPI again. The triple therapy is the treatment of choice of Helicobacter pylori infection. Patients with persistent Helicobacter pylori infection, after a first treatment, should be treated with a sequential treatment. PPI are effective in the prevention of gastroduodenal lesions and in the treatment of dyspeptic symptoms during NSAID treatment. IPP should be given to all patients presenting dyspeptic symptoms under NSAID or COX-2 administration.

Maladies peptiques [Progress in 2008 for acid related diseases]

The treatment of reflux disease did not change in the review period. PPI therapy remains the first line treatment and surgery the second line approach. Endoscopic anti-reflux procedures should be only performed in controlled studies. Beside the classic triple therapy, sequential treatment of Helicobacter pylori infection can today be considered as a first line therapy. PPI are effective in the prevention of gastroduodenal lesions and in the treatment of dyspeptic symptoms induced by NSAIDs treatment. Only patients younger then 65 years and without any risk factors do not need a preventive PPI prescription during classic NSAIDS treatment.

Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype.

Gastric cancer incidence and mortality decreased substantially over the last decades in most countries worldwide, with differences in the trends and distribution of the main topographies across regions. To monitor recent mortality trends (1980-2011) and to compute short-term predictions (2015) of gastric cancer mortality in selected countries worldwide, we analysed mortality data provided by the World Health Organization. We also analysed incidence of cardia and non-cardia cancers using data from Cancer Incidence in Five Continents (2003-2007). The joinpoint regression over the most recent calendar periods gave estimated annual percent changes (EAPC) around -3% for the European Union (EU) and major European countries, as well as in Japan and Korea, and around -2% in North America and major Latin American countries. In the United States of America (USA), EU and other major countries worldwide, the EAPC, however, were lower than in previous years. The predictions for 2015 show that a levelling off of rates is expected in the USA and a few other countries. The relative contribution of cardia and non-cardia gastric cancers to the overall number of cases varies widely, with a generally higher proportion of cardia cancers in countries with lower gastric cancer incidence and mortality rates (e.g. the USA, Canada and Denmark). Despite the favourable mortality trends worldwide, in some countries the declines are becoming less marked. There still is the need to control Helicobacter pylori infection and other risk factors, as well as to improve diagnosis and management, to further reduce the burden of gastric cancer.

The stomach cancer pooling (StoP) project: study design and presentation.

Gastric cancer affects about one million people per year worldwide, being the second leading cause of cancer mortality. The study of its etiology remains therefore a global issue as it may allow the identification of major targets, besides eradication of Helicobacter pylori infection, for primary prevention. It has however received little attention, given its comparatively low incidence in most high-income countries. We introduce a consortium of epidemiological investigations named the 'Stomach cancer Pooling (StoP) Project'. Twenty-two studies agreed to participate, for a total of over 9000 cases and 23 000 controls. Twenty studies have already shared the original data set. Of the patients, 40% are from Asia, 43% from Europe, and 17% from North America; 34% are women and 66% men; the median age is 61 years; 56% are from population-based case-control studies, 41% from hospital-based ones, and 3% from nested case-control studies derived from cohort investigations. Biological samples are available from 12 studies. The aim of the StoP Project is to analyze the role of lifestyle and genetic determinants in the etiology of gastric cancer through pooled analyses of individual-level data. The uniquely large data set will allow us to define and quantify the main effects of each risk factor of interest, including a number of infrequent habits, and to adequately address associations in subgroups of the population, as well as interaction within and between environmental and genetic factors. Further, we will carry out separate analyses according to different histotypes and subsites of gastric cancer, to identify potential different risk patterns and etiological characteristics.

Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas

CD95 (Fas/APO-1)-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas). However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis) related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95) was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells) was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03). The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1%). Histological examination revealed fundic type epithelium in 58.3% of cases, H. pylori was present in 50% and chronic inflammation in 66.7%. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7% of cases and Barrett's esophagus in 90% of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Expression of TERT in precancerous gastric lesions compared to gastric cancer

The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46% of IM, 50% of GU, and 79% of GC. The relative mean level of TERT mRNA after normalization with the β-actin reference gene and comparison with the respective adjacent normal mucosa was slightly increased in the IM and GU groups, 2.008 ± 2.605 and 2.730 ± 4.120, respectively, but high TERT mRNA expression was observed in the GC group (17.271 ± 33.852). However, there were no statistically significant differences between the three groups. TERT protein-positive immunostaining was observed in 38% of IM, 39% of GU, and 55% of GC. No association of TERT mRNA and protein expression with Helicobacter pylori infection or other clinicopathological variables was demonstrable, except for the incomplete type vs the complete type of IM. This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.

Health benefits of probiotics: are mixtures more effective than single strains?

PURPOSE: Most studies on probiotics utilise single strains, sometimes incorporated into yoghurts. There are fewer studies on efficacy of mixtures of probiotic strains. This review examines the evidence that (a) probiotic mixtures are beneficial for a range of health-related outcomes and (b) mixtures are more or less effective than their component strains administered separately. RESULTS: Mixtures of probiotics had beneficial effects on the end points including irritable bowel syndrome and gut function, diarrhoea, atopic disease, immune function and respiratory tract infections, gut microbiota modulation, inflammatory bowel disease and treatment of Helicobacter pylori infection. However, only 16 studies compared the effect of a mixture with that of its component strains separately, although in 12 cases (75%), the mixture was more effective. CONCLUSION: Probiotic mixtures appear to be effective against a wide range of end points. Based on a limited number of studies, multi-strain probiotics appear to show greater efficacy than single strains, including strains that are components of the mixtures themselves. However, whether this is due to synergistic interactions between strains or a consequence of the higher probiotic dose used in some studies is at present unclear.

Esophageal and gastric biopsies in symptomatic children and adolescents. Should both be performed?

This study investigated the relationship among the histological diagnosis of esophagitis and gastritis in children and adolescents with gastroesophageal reflux disease (GERD) and/or dyspepsia. Records of 366 patients submitted to endoscopic biopsies were reviewed. Two groups were analyzed: G1 n=258 with esophageal and gastric biopsies, G2 n=108 with gastric biopsies only. For total subjects median age (range) was 8.5y (2mo-19.9y). Helicobacter pylori infection was detected in 30.6 %, median age 12.5y for H pylori-infected and 5.5y for uninfected children. Histological esophagitis was found in 216/258 (83.7 %) and gastritis in 95/258 (36.8 %) of G1. Both biopsies were normal for 13.6 % cases. Normal gastric biopsies were associated with esophagitis in 128/ 163 (78.5 %) of G1, but gastritis was associated with normal esophageal biopsies in only 7/95 (7.4 %) (0<.001). Histological gastritis was found in 80/108 (74.1 %) of G2 patients. Therefore, for symptomatic children both biopsies are indicated.

Expression of TERT in precancerous gastric lesions compared to gastric cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-beta pro-inflammatory cytokine is not

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise da expressão da anexina-1 e galectina-1 na carcinogênese gástrica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Gastric cancer is associated with NOS2-954G/C polymorphism and environmental factors in a Brazilian population

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)