Expression of transforming growth factor beta-1 in gastric cancer and in the gastric mucosa of first-degree relatives of patients with gastric cancer

Transforming growth factors beta (TGF-β) constitute a family of polypeptide growth factors that control cell growth, cell differentiation and migration, as well as the formation of the extracellular matrix. Recent analyses revealed the overexpression of TGF-β1 in human gastric cancers and demonstrated increased cell proliferation in the stomach of patients with gastric cancer and their first-degree relatives. Using human gastric tissues obtained from patients with gastric cancer (n = 19), biopsies from healthy first-degree relatives of gastric cancer patients (n = 18) and healthy individuals (n = 19), we analysed the expression of TGF-β1 using the reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Fifteen of 19 patients with gastric cancer expressed TGF-β1 in the tumour. In 11 of these 15 cases TGF-β1 mRNA was also detectable in the non-tumourous stomach. Interestingly, all but two individuals with a first-degree relative diagnosed with gastric cancer exhibited TGF-β1 expression in either the antrum or corpus biopsy or both. In contrast, only one of 19 individuals without a family history of gastric cancer expressed TGF-β1 in the stomach (P< 0.0001). TGF-β1 expression is detectable in a large proportion of gastric cancers and in the stomach of healthy first-degree relatives of gastric cancer patients. Since individuals without gastric cancers in their family express TGF-β1 only in one of 19 cases, the induction of TGF-β1 expression in first-degree relatives of patients with gastric cancer points to the presence of specific molecular alterations in a subgroup of individuals with an increased risk of developing gastric cancer that may precede the development of gastric cancers. © 2000 Cancer Research Campaig

Diffuse duodenal nodular lymphoid hyperplasia: a large cohort of patients etiologically related to Helicobacter pylori infection

Abstract Background Nodular lymphoid hyperplasia of gastrointestinal tract is a rare disorder, often associated with immunodeficiency syndromes. There are no published reports of its association with Helicobacter pylori infection. Methods From March 2005 till February 2010, we prospectively followed all patients with diffuse duodenal nodular lymphoid hyperplasia (DDNLH). Patients underwent esophagogastroduodenoscopy with targeted biopsies, colonoscopy, and small bowel video capsule endoscopy. Duodenal nodular lesions were graded from 0 to 4 based on their size and density. Patients were screened for celiac sprue (IgA endomysial antibody), immunoglobulin abnormalities (immunoglobulin levels & serum protein electrophoresis), small intestine bacterial overgrowth (lactulose hydrogen breath test), and Helicobacter pylori infection (rapid urease test, and histological examination of gastric biopsies). Patients infected with Helicobacter pylori received sequential antibiotic therapy and eradication of infection was evaluated by 14C urea breath test. Follow up duodenoscopies with biopsies were performed to ascertain resolution of nodular lesions. Results Forty patients (Males 23, females 17; mean age ± 1SD 35.6 ± 14.6 years) with DDNLH were studied. Patients presented with epigastric pain, vomiting, and weight loss. Esophagogastroduodenoscopy showed diffuse nodular lesions (size varying from 2 to 5 mm or more) of varying grades (mean score ± 1SD 2.70 ± 0.84) involving postbulbar duodenum. Video capsule endoscopies revealed nodular disease exclusively limited to duodenum. None of the patients had immunoglobulin deficiency or small intestine bacterial overgrowth or positive IgA endomysial antibodies. All patients were infected with Helicobacter pylori infection. Sequential antibiotic therapy eradicated Helicobacter pylori infection in 26 patients. Follow up duodenoscopies in these patients showed significant reduction of duodenal nodular lesions score (2.69 ± 0.79 to 1.50 ± 1.10; p Helicobacter pylori infection showed no significant reduction of nodular lesions score (2.71 ± 0.96 to 2.64 ± 1.15; p = 0.58). Nodules partially regressed in score in 2 patients, showed no interval change in 10 patients and progressed in 2 patients. Conclusions We report on a large cohort of patients with DDNLH, etiologically related to Helicobacter pylori infection.</p

The association of serum lipids with the histological pattern of rectosigmoid adenoma in Taiwanese adults

<p>Abstract</p> <p>Background</p> <p>The mortality rate of colorectal cancer ranks third behind lung and hepatic cancer in Taiwan. Colorectal cancer mostly arises from adenomatous polyps of left colon. The aim of our study was to examine the association of serum lipids with the histological pattern of rectosigmoid adenoma.</p> <p>Methods</p> <p>There were 2,506 eligible examinees aged 20 and above who underwent sigmoidoscopy as a screening examination in National Cheng Kung University Hospital between January 2003 and October 2006. They were classified into three groups: tubular adenoma (333 subjects), villous-rich (tubulovillous/villous) adenoma (53 subjects) and normal (2,120 subjects). We defined high total cholesterol (TC) as a level ≧200 mg/dl, low high-density lipoprotein cholesterol (HDL-C) as a level <40 mg/dL, and high triglyceride (TG) as a level ≧200 mg/dl according to the third report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Adenoma histology was classified as tubular, tubulovillous and villous according to the proportion of villous part.</p> <p>Results</p> <p>Among the study population, 333 subjects (13.3%) had tubular adenomas and 53 subjects (2.1%) had villous-rich adenomas. The odds ratio (OR) for villous-rich adenoma in subjects with TG≧200 mg/dL compared to those with TG < 200 mg/dL was 3.20 (95% confidence interval [CI]:1.71-6.01), after adjusting for age, gender, general obesity, central obesity, diabetes, hypertension, smoking, and alcohol consumption. If further taking high TC and low HDL-C into consideration, the OR was 4.42 (95% CI:2.03-9.63).</p> <p>Conclusions</p> <p>Our study showed that subjects with high serum TG tended to have a higher risk of tubulovillous/villous adenoma in rectosigmoid colon. Therefore, reducing the serum TG level might be one method to prevent the incidence of colorectal cancer.</p

Na⁺/Ca²⁺ countertransport in plasma membrane of rat pancreatic acinar cells

The presence of a coupled Na+/Ca2+ exchange system has been demonstrated in plasma membrane vesicles from rat pancreatic acinar cells. Na+/Ca2+ exchange was investigated by measuring 45Ca2+ uptake and 45Ca2+ efflux in the presence of sodium gradients and at different electrical potential differences across the membrane (= delta phi) in the presence of sodium. Plasma membranes were prepared by a MgCl2 precipitation method and characterized by marker enzyme distribution. When compared to the total homogenate, the typical marker for the plasma membrane, (Na+ + K+)-ATPase was enriched by 23-fold. Markers for the endoplasmic reticulum, such as RNA and NADPH cytochrome c reductase, as well as for mitochondria, the cytochrome c oxidase, were reduced by twofold, threefold and 10-fold, respectively. For the Na+/Ca2+ countertransport system, the Ca2+ uptake after 1 min of incubation was half-maximal at 0.62 mumol/liter Ca2+ and at 20 mmol/liter Na+ concentration and maximal at 10 mumol/liter Ca2+ and 150 mmol/liter Na+ concentration, respectively. When Na+ was replaced by Li+, maximal Ca2+ uptake was 75% as compared to that in the presence of Na+. Amiloride (10-3 mol/liter) at 200 mmol/liter Na+ did not inhibit Na+/Ca2+ countertransport, whereas at low Na+ concentration (25 mmol/liter) amiloride exhibited dose-dependent inhibition to be 62% at 10-2 mol/liter. CFCCP (10-5 mol/liter) did not influence Na+/Ca2+ countertransport. Monensin inhibited dose dependently; at a concentration of 5 X 10-6 mol/liter inhibition was 80%. A SCN- or K+ diffusion potential (= delta phi), being positive at the vesicle inside, stimulated calcium uptake in the presence of sodium suggesting that Na+/Ca2+ countertransport operates electrogenically, i.e. with a stoichiometry higher than 2 Na+ for 1 Ca2+. In the absence of Na+, delta phi did not promote Ca2+ uptake. We conclude that in addition to ATP-dependent Ca2+ outward transport as characterized previously (E. Bayerdörffer, L. Eckhardt, W. Haase & I. Schulz, 1985, J. Membrane Biol. 84:45-60) the Na+/Ca2+ countertransport system, as characterized in this study, represents a second transport system for the extrusion of calcium from the cell. Furthermore, the high affinity for calcium suggests that this system might participate in the regulation of the cytosolic free Ca2+ level