gastrin-17 and Peptic-Ulcer

Aphton is developing an anti-gastrin vaccine [Anti-gastrin 17 immunogen, G17DT, Gastrimmune], which neutralises the gastrin 17 hormone and the Gly-G17 hormone. Gastrin 17 is a growth factor for pancreatic, stomach and colorectal cancers, and a potent stimulator of gastric acid secretion.The anti-gastrin immunogen, G17DT, consists of a large carrier protein, called Diptheria Toxoid (DT). A synthetic peptide, which is similar to a portion of the gastrin 17 hormone (GT), is attached to the carrier protein. These are then contained in a liquid suspension vehicle. When administered to patients, G17DT induces an immune response producing antibodies, which cross-react and neutralise the target hormone thus preventing its interaction with disease-causing or -participating cells. Aphton has entered into an agreement with Aventis Pasteur for the marketing of G17DT in all human cancer indications in North America and Europe. Under the terms of the agreement, Aphton is responsible for product development, clinical trials and regulatory agency approvals. The agreement was originally with Pasteur Mérieux Connaught, a subsidiary of Rhône-Poulenc. However, in December 1999, Rhône-Poulenc merged with Hoechst to form Aventis. As a result of the merger, Pasteur Mérieux Connaught underwent a name change to Aventis Pasteur. In July 2002, Aphton announced that it would negotiate with companies wanting to licence the vaccine in territories other than North America and Europe. In February 2003, Aphton announced it had received fast track designation for G17DT in combination with cisplatin and fluorouracil for use in stage IV gastric cancer to improve overall survival. In July 2002, the US FDA granted G17DT orphan drug status for the treatment of gastric cancer, an indication that was broader than the indication Aphton originally sought. The vaccine was also granted orphan drug status in Australia for gastric cancer in December 2002. In July 2002, Aphton announced that the US FDA had granted G17DT orphan drug status for the treatment of adenocarcinoma of the pancreas. In September 2002, the US FDA also granted G17DT, used in combination with gemcitabine, fast track status for the treatment of pancreatic cancer patients. In addition, the vaccine was also granted orphan drug status in Australia for pancreatic cancer in December 2002. In March 2003, Aphton announced that the Committee for Orphan Medicinal Products had recommended to the European Commission that G17DT be granted orph

Topics: Animals; Cancer Vaccines; Clinical Trials as Topic; Colorectal Neoplasms; Gastrins; Humans; Orphan Drug Production; Pancreatic Neoplasms; Peptic Ulcer; Rats; Stomach Neoplasms; Vaccines

On the basis of the levels of serum pepsinogen I (S-PGI) and gastrin-17 (S-G-17) as well as Helicobacter pylori - antibodies assayed from a blood sample it is possible to establish with high sensitivity and specificity whether the patient has gastritis, whether the gastritis is atrophic or not and in which part of the stomach the atrophic changes are located. The test enables the identification of patients whose risk of gastric cancer, of the consequences of vitamin B12 deficiency (e.g. elevated levels of homocysteine) or of peptic ulcer is considerably increased and who can then undergo gastroscopy. It also facilitates the diagnosis of non-atrophic Helicobacter gastritis enabling treatment before endoscopy.

Topics: Finland; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Pepsinogen A; Peptic Ulcer; Stomach Neoplasms; Vitamin B 12 Deficiency

The article presents the results of the first Russian open randomized comparative multicenter study on the effectiveness of Famotidine in the prevention of NSAID-gastropathy--Barrier. In addition, were showen the results of studies of the drugs effect used for prevention of NSAID gastropathy (Famotidine, Lansoprazole, Misoprostol) for the synthesis of prostaglandins in the gastric mucosa in patients with osteoarthritis. Was shown the impact of alternative anti-inflammatory drug on the basis of an extract of ginger as joint pain, and the mucous upper gastrointestinal tract in patients with osteoarthritis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Diclofenac; Famotidine; Gastric Mucosa; Gastrins; Humans; Middle Aged; Peptic Ulcer; Prostaglandins; Treatment Outcome

Methods for the measure of gastric acid secretion include invasive and non-invasive tests. The gold-standard to measure the acid output is the collection of gastric after in basal condition (Basal Acid Output, B.A.O.) and after an i.m. injection of pentagastrin (Maximal Acid Output, M.A.O.). However, direct measurement of gastric acid production is out of order in clinical practice, but many GI symptoms are claimed to be related with acid disorders and empirically cured. Hypochlorhydria is associated with precancerous conditions such as chronic atrophic gastritis (CAG). Acid measurement with non-invasive methods (pepsinogens) is supported by international guidelines.

Topics: Achlorhydria; Biomarkers; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastritis, Atrophic; Humans; Pentagastrin; Pepsinogens; Peptic Ulcer; Precancerous Conditions

Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastrins; Gastritis; Gene Frequency; Genetic Predisposition to Disease; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Polymorphism, Single Nucleotide; Risk Factors; Stomach Neoplasms; Toll-Like Receptor 4; Young Adult

To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa: i.e. those with Helicobacter pylori (H pylori) gastritis or atrophic gastritis, who have a high risk of gastric cancer or peptic ulcer diseases.. Among 162 Japanese outpatients, pepsinogen I (Pg I) and II (Pg II) were measured using a conventional Japanese technique, and the European GastroPanel examination (Pg I and Pg II, gastrin-17 and H pylori antibodies). Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa, H pylori non-atrophic gastritis or atrophic gastritis.. Pg I and Pg II assays with the GastroPanel and the Japanese method showed a highly significant correlation. For methodological reasons, however, serum Pg I, but not Pg II, was twice as high with the GastroPanel test as with the Japanese test. The biomarker assays revealed that 5% of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies. GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis. When compared to the endoscopic biopsy findings, the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy, 95% sensitivity and 93% specificity.. Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Topics: Adult; Aged; Biopsy; Diagnosis, Differential; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Middle Aged; Outpatients; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Prevalence; Reference Values; Risk Factors; Stomach; Stomach Neoplasms; Young Adult