Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal and gastric tumors are often considered as a single group: they share similar symptoms - upper GI endoscopy with a flexible video-endoscope is the gold standard procedure of detection - similar techniques of endotherapy for cure or palliation are offered for both types of tumors. When the endoscopic procedure is performed for a superficial cancer or its precursors, with a curative intent, endoscopic mucosal resection (EMR) is generally preferred to mucosal ablation with a thermal (Nd:YAG) or non-thermal (photodynamic therapy) procedure. In addition to esophageal squamous cell cancer and gastric cancer, new indications of EMR arise in the Barrett esophagus. Guidelines for safe indications concern diameter, polypoid or non polypoid morphology with the subtypes elevated, flat and depressed, and depth of invasion. A superficial invasion in the sub-mucosa is a relative contra-indication in the esophagus, but not in the stomach. The technique of EMR is now codified with an injection into the submucosa for lifting the lesion and either suction with a cap, grasping with a forceps if a 2 channel instrument is used, or tissue incision with a needle knife. En bloc, gives better results than piecemeal resection. The most frequent complication is bleeding. When legitimate indications are respected, the results of EMR are equivalent to those of surgical resection and have reached the consensus level. The major indication in palliation is the relief of dysphagia from malignant esophageal obstruction. Increased indications are proposed for malignant pyloric obstruction. Multiple models of metal expandable and coated stents with appropriate balance between rigidity and flexibility (nitinol alloy) and enough expansive radial force are now offered. After stenting the survival period is short and there is a toll of complications.
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PMID:Treatment of esophagogastric tumors. 1256 Oct 5

From a clinical and biological point of view, the term "adenocarcinoma of the esophagogastric junction" (AEG) encompasses several distinct tumor entities. The topographic anatomic classification into adenocarcinoma of the distal esophagus (AEG I), true carcinoma of the cardia (AEG II), and subcardiac gastric cancer (AEG III) also reflects differences regarding the pathogenesis of these tumors and is increasingly accepted worldwide. Associated Barrett's esophagus, which usually develops as a consequence of chronic gastroesophageal reflux, can be documented in practically all patients with AEG I tumors and constitutes the most important precancerous lesion. A metaplasia-dysplasia-carcinoma sequence has been confirmed for these tumors. Barrett's esophagus is thus considered a model for studies on carcinogenesis and the prevention of esophageal adenocarcinoma. Its pathogenetic role in AEG II and III tumors must, however, be discussed differently. Our own experience shows that pathogenetic mechanisms similar to those in AEG I tumors may be present in up to 30% of tumors classified as AEG II. The majority of AEG II tumors, however, show morphologic, biologic and pathogenetic similarities with AEG III tumors and proximal gastric cancer.
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PMID:[Carcinoma of the oesophagogastric junction and Barrett's esophagus: an almost clear oncologic model?]. 1292 90

There is a clear relationship between Barrett's oesophagus and oesophageal adenocarcinoma, and between Helicobacter pylori and gastric cancer, but the histogenesis of cardiac adenocarcinomas is unknown. Some clues as to possible disease associations may be provided by the pattern of gastritis. In our study, we analysed gastritis associated with oesophageal, cardiac and gastric adenocarcinomas according to the Sydney classification. Chronic gastritis was more common in gastric (88%) than in cardiac (56%) and oesophageal adenocarcinomas (38%). H. pylori was significantly more prevalent in gastric (73%) than in cardiac (34%) or oesophageal (21%) adenocarcinomas. Our results show that factors other than H. pylori must be involved in the histogenesis of cardiac adenocarcinomas. As the pattern of gastritis and the clinical features of cardiac adenocarcinomas are more comparable to oesophageal carcinomas than gastric carcinomas, we speculate that most of these tumours share similar aetiological factors with oesophageal carcinomas.
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PMID:Are carcinomas of the cardia oesophageal or gastric adenocarcinomas? 1460 34

Since the rediscovery of Helicobacter pylori two decades ago, it has become increasingly clear that the true relationships between this organism and diseases of the upper gastrointestinal tract are highly complex. H. pylori colonization is a strong risk factor for peptic ulceration and distal gastric cancer; however, gastritis has no adverse consequences for most hosts, and the prevalence of H. pylori is inversely related to gastroesophageal reflux disease (GERD) and its sequelae, which include Barrett's esophagus and esophageal adenocarcinoma. One clinical implication stemming from these data is that H. pylori eradication may not be appropriate in certain human populations due to potential beneficial effects conferred by persistent gastric inflammation. However, the majority of published intervention trials indicate that H. pylori treatment neither leads to the development of clinically significant de novo esophagitis nor exacerbates existing reflux disease. Superimposed upon these observations are reports that long-term acid suppression induced by proton-pump inhibitors (PPIs) in conjunction with H. pylori colonization may enhance the development of atrophic gastritis, a well-recognized histologic step in the progression to intestinal-type gastric cancer. Therefore, current evidence-based recommendations regarding management of H. pylori-positive individuals with GERD include the following. H. pylori should not be treated with the intent to either improve reflux symptoms or prevent the development of reflux complications. However, if patients are to receive long-term acid suppressive therapy, they should be tested for H. pylori and treated if positive, due to the potential for PPIs to accelerate atrophy within H. pylori-infected mucosa. Optimal first-line regimens in this country consist of a PPI in combination with clarithromycin and either amoxicillin or metronidazole (triple therapy) for at least 7, but preferably 10, days. Because the most effective second-line regimens contain metronidazole, it is advisable to use amoxicillin instead of metronidazole as first-line therapy in order to optimize results should subsequent therapy be required. If first-line regimens fail to eliminate H. pylori, patients should receive quadruple therapy consisting of a PPI, bismuth subsalicylate, metronidazole, and tetracycline for 14 days. Due to the availability and accuracy of noninvasive diagnostic tests for H. pylori, it is recommended that successful cure be confirmed after intervention.
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PMID:Helicobacter pylori and Gastroesophageal Reflux Disease. 1472 39

Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.
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PMID:Personal view: to treat or not to treat? Helicobacter pylori and gastro-oesophageal reflux disease - an alternative hypothesis. 1498 71

The human monoclonal antibody PAM-1 was isolated from a patient with stomach cancer. The germ-line coded IgM antibody identifies a recently described 130 kDa variant of CFR-1 (cysteine-rich fibroblast growth factor receptor 1). This CFR-1/PAM-1 receptor is post-transcriptionally modified and over-expressed on human epithelial tumors and carcinoma pre-cancer lesions such as H. pylori induced gastritis, intestinal metaplasia and dysplasia of the stomach, ulcerative colitis-related dysplasia and adenomas of the colon, Barrett metaplasia and dysplasia of the esophagus, squamous cell metaplasia and dysplasia of the lung and cervical intraepithelial neoplasia. Furthermore, the expression of CFR-1/PAM-1 correlates with the proliferation rate and increases with the grade of malignancy. This study demonstrates that the human monoclonal antibody PAM-1 inhibits cell growth and induces apoptosis, in vitro and in vivo. Both, the unique tumor-specific expression of the CFR-1/PAM-1 receptor and the growth inhibitory effect of the PAM-1 antibody makes this combination a good diagnostic and therapeutic tool for all kinds of epithelial cancers and precursor lesions.
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PMID:CFR-1 receptor as target for tumor-specific apoptosis induced by the natural human monoclonal antibody PAM-1. 1501 Aug 72

Gastro-oesophageal reflux disease (GORD) and Helicobacter pylori infection are both common in Western countries. A recently published meta-analysis has shown an association between an absence of H. pylori infection and GORD symptoms. Infection with cagA-positive H. pylori strains is a causative factor for the development of duodenal ulcer and is a risk factor for gastric cancer. Data about a protective role of cagA-positive H. pylori strains against more severe reflux oesophagitis are documented in several studies, but questioned by some other studies. There is a need for further studies to clear the definite role of cagA-positive H. pylori strains in severe reflux oesophagitis and their possible effect on the development of Barrett's adenocarcinoma. The role of Helicobacter pylori in gastro-oesophageal reflux disease (GORD) is still discussed controversially. Different factors might be responsible for the remarkably heterogeneous results of previously performed studies (e.g. location, environmental factors and different virulence factors of H. pylori strains). A very recently published meta-analysis has shown a significant association between the absence of H. pylori infection and GORD symptoms, and a positive correlation between anti-H. pylori therapy and the occurrence of both de-novo and rebound/exacerbated GORD. The results of this meta-analysis are questioned by some authors because of single larger trials and geographical variations of the studies analysed. Data on the role of the cytotoxic-associated antigen (cagA)-positive H. pylori strains are contradictory. Several studies have provided evidence supporting the protecting role of cagA-positive H. pylori strains against GORD, but these results were not confirmed by all studies. A multitude of patients suffer from H. pylori infection and GORD, simultaneously. Therefore, further studies are needed to clearly answer the question whether infection with cagA-positive H. pylori strains, which bear a well-documented risk for gastric cancer and gastro-duodenal ulcer, is really helpful against more severe reflux oesophagitis and, in consequence, perhaps protective against Barrett's oesophagus and Barrett's adenocarcinoma.
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PMID:cagA-positive Helicobacter pylori strains and gastro-oesophageal reflux disease: still puzzling? 1520 76

Through previous large-scale gene expression profiling we identified a transcript that was abundant in normal stomach and down-regulated in gastric cancer. Genes expressed at similar levels included gastrin, MUC5 and pS2, which are important in gastric function. We aimed to characterise this candidate, gastrokine 1 (GKN1), at mRNA, DNA, protein and tissue levels. The gene was studied in human, mouse, rat and cow, and was highly conserved across these species. The mRNA transcripts averaged 750 bp in length. The human, mouse and rat genes all contained six exons spanning 6 kb, and were located on chromosomes 2, 6 and 4 respectively. The full-length translation products were 183-185 amino acids long, reducing to the mature protein of 18 kDa following signal peptide cleavage; these predictions were confirmed by Western blotting. Tagged gastrokine 1 yielded granular cytoplasmic staining with perinuclear accentuation, representing the Golgi apparatus, in keeping with secretion or expression on the extracellular surface. Gene expression in tissues was profiled extensively by Northern blotting, in situ hybridisation and immunohistochemistry. Gastrokine 1 was highly expressed in normal stomach, where it was located in the superficial/foveolar gastric epithelium, but was absent from gastric carcinomas. Outwith the stomach, gastrokine 1 was found only in epithelia showing gastric metaplasia eg Barrett's oesophagus, the ulcer-associated cell lineage and ovarian mucinous neoplasms. In conclusion, we have characterised gastrokine 1, previously known as CA11, AMP-18 or foveolin. Its abundance in, and specificity for, native or metaplastic gastric epithelium, down-regulation in gastric carcinoma and evolutionary conservation suggest that this gene is physiologically important in the stomach. The function of gastrokine 1 is unknown but a role in mucosal protection is postulated.
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PMID:Gastrokine 1 is abundantly and specifically expressed in superficial gastric epithelium, down-regulated in gastric carcinoma, and shows high evolutionary conservation. 1522 38

Premalignant esophagogastric (EG) lesions develop against a background of chronic inflammation, called a premalignant condition. For esophageal squamous cell cancer, causal factors include alcohol, tobacco, hot beverages, oral consumption of opioids, and probably infectious agents. For adenocarcinoma in the Barrett's esophagus (BE), gastroesophageal reflux disease (GERD) is the principal causal factor. At the EG junction, adenocarcinoma arises either from the esophagus or from the proximal stomach (cardia). In the distal stomach, chronic gastritis with atrophy is the premalignant condition related to Helicobacter pylori infection. A high intake of salt and low intake of antioxidants also play a role. The histopathology of EG premalignant lesions is now included in the groups low-grade and high-grade intraepithelial neoplasia (IEN) of the revised Vienna classification. Endoscopy is the gold standard for detection of the lesions at the preclinical stage and their appearance is described in subtypes of the type 0 of the Japanese classification, with a distinction between protruding and nonprotruding lesions. There is a priority for primary prevention of causal factors rather than for mass screening, which is justified only in Japan for the prevention of stomach cancer. The trend to early detection of premalignant lesions justifies the development of mini-invasive endoscopic procedures of treatment.
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PMID:Premalignant lesions of the esophagogastric mucosa. 1529 42

Gastric cancer has been declining for more than half a century, whereas the incidence of oesophageal cancer is increasing rapidly. The histopathological subtype is also changing with a predominance of oesophageal adenocarcinoma compared with squamous carcinoma. The reasons for these epidemiological changes are not clear, although population-based data have implicated gastro-oesophageal reflux disease as a risk factor. In susceptible individuals reflux of duodeno-gastric contents can lead to the development of a columnar-lined oesophagus, commonly called Barrett's oesophagus. This can then progress to adenocarcinoma via a metaplasia-dysplasia-carcinoma sequence. At the current time, the mortality from oesophageal adenocarcinoma exceeds 80% at 5 years. Therefore, endoscopic surveillance programmes have been generally recommended for patients with Barrett's oesophagus in an attempt to detect early, curable lesions. Unfortunately these programmes are cumbersome and costly and have not yet been proved to reduce population mortality. In order to improve patient outcomes we need to be able to identify patients at high risk and to understand the triggers for disease progression. There is mounting evidence that there is an underlying genetic susceptibility to Barrett's oesophagus and oesophageal adenocarcinoma. However, this is likely to be as a result of multiple low penetrance susceptibility genes which have yet to be identified. Once patients are identified as having Barrett's oesophagus their chance for developing adenocarcinoma is in the order of 0.5%-1% per year. The histological assessment of dysplasia as a predictor of cancer development is highly subjective. Therefore multiple, specific somatic mutations in the tissue have been investigated as potential biomarkers. The most promising markers to date are the presence of aneuploidy, loss of heterozygosity of p53 and cyclin D1 overexpression. However, a study of evolutionary relationships suggest that mutations occur in no obligate order. Combinatorial approaches are therefore being advocated which include genomic profiling or the use of a panel of molecular markers in order to define the common molecular signatures that can then be used to predict malignant progression. An alternative approach would be to use markers for the final common pathway following genetic instability, which is the loss of proliferative control. We have demonstrated an increase in the expression of a novel proliferation marker, Mcm2, which occurs during the malignant progression of Barrett's oesophagus. These Mcm2-expressing cells are detectable on the surface, and hence a cytological approach may be applicable. In view of the role of reflux components in the pathogenesis of Barrett's oesophagus the effect of acid and bile on the cell phenotype have been studied. These studies have demonstrated that pulsatile acid and bile exposure induce cell proliferation. The mechanism for the hyperproliferative response appears to involve p38 mitogen activated protein kinase (MAPK) pathways as well as protein kinase C (PKC) and cyclo-oxygenases. A clinical implication of the laboratory studies is that suppression of acid and bile may need to be profound in order to suppress cell proliferation and, by inference, ultimately prevent the development of dysplasia. There is some support for this concept from short-term clinical studies, and a large randomised chemoprevention trial is being instigated which will evaluate the effect of proton pump inhibitors with or without aspirin. Given the epidemic increase in oesophageal adenocarcinoma and the dismal 5-year mortality rate, a radical approach is necessary to prevent cancer development in individuals with pre-malignant lesions.
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PMID:Genetics and prevention of oesophageal adenocarcinoma. 1564 81


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