Interleukin 1 beta gene promoter SNPs are associated with risk of pancreatic cancer.

Epidemiological and experimental data demonstrate, that inflammation contributes significantly to pancreatic carcinogenesis. IL1beta, a pleiotropic cytokine produced by inflammatory cells and tumor cells, promotes cancer progression. Single nucleotide polymorphisms (SNPs) of the IL1beta promoter were found to be associated with an increased risk for certain cancers.

Correlation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase expression in ileal carcinoids, lymph nodes and liver metastasis with prognosis and survival.

Purpose: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis.

Toll-like receptor-dependent activation of antigen-presenting cells affects adaptive immunity to Helicobacter pylori.

Background & Aims: Recognition of infection leads to induction of adaptive immunity through activation of antigen-presenting cells (APCs). Among APCs, dendritic cells (DCs) have the unique capacity to deliver antigens from the periphery to T cells in secondary lymphoid organs.

Methods: We analyzed molecular mechanisms of the Helicobacter pylori-induced APC activation in vitro and investigated the influence of Myd88 signaling on the phenotype of adaptive immunity to H pylori in a murine infection model.

Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2.

Regulatory T cells (Treg) are vital in maintaining the homeostasis of immune reactions. In chronic infections, such as schistosomiasis, it remains unclear whether engagement of the TLR family is required to induce Treg activity. Thus, we performed in vivo studies using TLR2-/- mice infected with Schistosoma mansoni and found elevated immunopathology, decreased egg burden and extended antigen-specific Th1 responses.

Fox-P3-positive regulatory T cells are present in the skin of generalized atopic eczema patients and are not particularly affected by medium-dose UVA1 therapy.

Background: Regulatory T cells (T-reg cells) have been described as an important cell population in the UV treatment of inflammatory skin diseases.

Methods: We have treated five patients with generalized atopic eczema (AE) using medium-dose (15 cycles of 50 J/cm(2), total dose of 750 J/cm(2)) UVA1 therapy and have analyzed the skin-infiltrating T-cellular subsets before and after therapy. Skin biopsies were split for immunohistochemistry and Real-time PCR and analyzed for CD4, Fox-P3, GATA-3, and IL-10 transcription as well as for CD3, CD4, CD152, Fox-P3, and GITR staining.

Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase.

Background & Aims: Helicobacter pylori colonizes the human gastric mucosa of >50% of the world's population. Most of the patients have no overt clinical symptoms. However, the infection is invariably associated with the development of active chronic gastritis, leading in some cases to the development of peptic ulcer disease, distal gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma.

Lead-like, drug-like or "Pub-like": how different are they?

Academic and industrial research continues to be focused on discovering new classes of compounds based on HTS. Post-HTS analyses need to prioritize compounds that are progressed to chemical probe or lead status. We report trends in probe, lead and drug discovery by examining the following categories of compounds: 385 leads and the 541 drugs that emerged from them; "active" (152) and "inactive" (1488) compounds from the Molecular Libraries Initiative Small Molecule Repository (MLSMR) tested by HTS; "active" (46) and "inactive" (72) compounds from Nature Chemical Biology (NCB) tested by HTS; compounds in the drug development phase (I, II, III and launched), as indexed in MDDR; and medicinal chemistry compounds from WOMBAT, separated into high-activity (5,784 compounds with nanomolar activity or better) and low-activity (30,690 with micromolar activity or less).

Conjugative transfer of chromosomally encoded antibiotic resistance from Helicobacter pylori to Campylobacter jejuni.

Many strains of Helicobacter pylori are naturally competent for transformation and able to transfer chromosomal DNA among different isolates using a conjugation-like mechanism. In this study, we sought to determine whether H. pylori can transfer DNA into Campylobacter jejuni, a closely related species of the Campylobacterales group.

Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms.

Background: Expression of the Helicobacter pylori outer membrane protein HopH is regulated by phase variation within a CT dinucleotide repeat motif of the hopH gene.

Methods: To investigate the importance of HopH for bacterial pathogenicity, we performed a detailed functional genomic and population-based genetic characterization of this contingency locus.

Results: Sequencing of hopH in H.

Lack of RUNX3 regulation in human gastric cancer.

It has been proposed that the transcription factor RUNX3 is the product of a gastric tumour suppressor gene. We examined RUNX3 expression in gastric biopsies from 105 patients with different histological presentations. Surprisingly, immunohistochemical staining detected RUNX3 protein expression only in infiltrating leukocytes but not in the gastric epithelium.

CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo.

Background & Aims: Helicobacter pylori infects more than half of the world's population. In contrast to most other pathogens, the microbe persists for the virtual life of its host. It is unclear why the immune system is unable to eliminate the infection, but recent studies suggested that CD4+/CD25+/Foxp3+ regulatory T cells may be involved in this process.

VacA-associated inhibition of T-cell function: reviewed and reconsidered.

Chronic Helicobacter pylori infection is characterized by dense infiltration of the mucosa with neutrophilic granulocytes, lymphocytes, and monocytes/macrophages. Among these different cell types, T-lymphocytes are the most intriguing and crucial cells for the elimination of the bacteria. Previous studies have elucidated possible mechanisms on how bacteria could interfere with the human immune response and claimed that especially the secreted vacuolating toxin VacA may be responsible for the chronic persistence of the bacteria.

Targeting alternatively spliced sequence features for cancer diagnosis and therapeutics.

Alternative splicing is emerging as a major new mechanism of functional regulation in mammals, and there is increasing evidence that human cancers often involve significant changes in alternative splicing. In some cases, these changes contribute functionally to the maintenance of the transformed state and could be useful as novel targets for anticancer therapy. In other cases, they reflect changes due to tumorigenesis and could be useful for diagnostic purposes.

A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells.

Background & Aims: Although Helicobacter pylori is recognized by the human immune system, the bacteria are not eliminated and lead to a chronic inflammation of the gastric mucosa.

Methods: We investigated the interaction of H. pylori with human lymphocytes.

Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries.

Helicobacter pylori strains harboring the vacAs1, cagA and babA2 have been associated with ulcer disease (UD). We compared the prevalence of these different genotypes and adhesive properties in H. pylori infected patients with UD in four European countries.

Expression of tumor necrosis factor- alpha -related apoptosis-inducing ligand and its proapoptotic receptors is down-regulated during gastric infection with virulent cagA+/vacAs1+ Helicobacter pylori strains.

Background: Infection of the gastric mucosa with Helicobacter pylori leads to increased apoptosis. Cytokines and receptors of the tumor necrosis factor (TNF) family are known to be involved in this process. The role that the death-inducing TNF- alpha -related apoptosis-inducing ligand (TRAIL) and its receptors play, in the context of H.

Isolation and receptor profiling of ileal enterochromaffin cells.

Aim And Methods: Enterochromaffin (EC) cells, interspersed throughout the gastrointestinal mucosa, provide most of the serotonin of the body and control intestinal motility, secretion and absorption. We purified EC cells from the rat ileum by a combination of elutriation and density gradient centrifugation in order to characterize the function of this important cell type.

Results: Immunostaining showed that there were 84% serotonin-positive cells in the highly enriched EC fraction as compared with 12% in unfractionated cells, yielding a approximately sevenfold enrichment.

Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection.

Background And Aims: Recent studies linked cytokine gene polymorphisms to H pylori related gastric cancer development. The current study evaluated the role of cytokine gene polymorphisms for mucosal cytokine expression, the gastric inflammatory response, and bacterial colonisation during H pylori infection.

Patients And Methods: In 207 H pylori infected patients with chronic gastritis, polymorphisms at different loci of the interleukin (IL)-10, IL-1B, IL-1 receptor antagonist (IL-1RN), tumour necrosis factor (TNF)-A, and interferon (IFN)-G genes were genotyped by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR.

Human dendritic cells respond to Helicobacter pylori, promoting NK cell and Th1-effector responses in vitro.

Helicobacter pylori infection leads to chronic gastric inflammation. The current study determined the response of human APCs, NK cells, and T cells toward the bacteria in vitro. Human monocyte-derived dendritic cells (DC) were incubated with bacteria for 48 h.

Identification of a genetic marker of Helicobacter pylori strains involved in gastric extranodal marginal zone B cell lymphoma of the MALT-type.

Background And Aims: Gastric extranodal marginal zone B cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type (MZBL) is a rare complication of Helicobacter pylori infection. Currently, no bacterial factor has been associated with the development of this disease. Our aim was to identify genes associated with lymphoma development.

Toll-like receptor expression in human keratinocytes: nuclear factor kappaB controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but not toll-like receptor 4 or platelet activating factor receptor dependent.

Cultured primary human keratinocytes were screened for their expression of various members of the toll-like receptor (TLR) family. Keratinocytes were found to constitutively express TLR1, TLR2, TLR3, TLR5, and TLR9 but not TLR4, TLR6, TLR7, TLR8, or TLR10 as shown by polymerase chain reaction analysis. The expression of the crucial receptor for signaling of staphylococcal compounds TLR2 was also confirmed by immunohistochemistry, in contrast to TLR4, which showed a negative staining pattern.