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Other cancers in patients with gastric MALT lymphoma.

Patients with Hodgkin's disease and nodal non-Hodgkin's lymphomas seem to have an excess risk for other cancers. A high incidence of other cancers has also been found in some series of patients with gastric MALT lymphomas. In a series of 136 patients with gastric MALT lymphomas the occurrence and features of other cancers have been described. In order to evaluate their occurrence statistically (excluding skin cancers) standard incidence ratios (SRI) have been calculated, using the incidence rates of a Cancer Registry in Spain as a reference. A Cox's multivariate proportional hazard model was fitted in order to evaluate the influence of age, sex, histological grade and treatment with chemotherapy or chemotherapy plus radiotherapy in the development of other non-skin cancers occurring after the diagnosis of MALT lymphoma. Other cancers were detected in 16 of the 136 patients (11.7%); the other cancer was detected prior to MALT gastric lymphoma in 6 patients (4.41%), concomitantly in 4 (2.9%) and after diagnosis of the lymphoma in 6 (4.41%). Other cancers occurred in 14.4% of the male and in 8.3% of the female patients; in 12% of the patients with low grade and in 11% of the patients with high grade lymphomas. Of the 6 cancers that occurred after diagnosis of the gastric lymphoma, 3 did in the 80 patients (3.7%) that had been treated with chemotherapy, 1 in the 3 cases (33%) treated with chemotherapy and radiotherapy and 2 in the 53 patients (3.7%) who had not received chemotherapy or radiotherapy. The most frequent other cancers were lymphoid neoplasms and gastric carcinoma. There was not an excess of other cancers in the whole cohort or in the sex or histological grade strata. There was an excess close to significance (SIR =2.59; 95% CI:0.98-6.88) in the patients under 50 years of age. In the Cox's analysis, age, sex, histological grade and treatment did not influence the occurrence of other cancers after the diagnosis of lymphoma. In conclusion, in patients with gastric MALT lymphoma other cancers also occur. An excess incidence was not demonstrated, although it may exist in patients under 50 years. Of special importance is the occurrence of gastric cancer that appears concomitantly or after gastric lymphoma.

Adenocarcinoma↗

Interaction of gene effects with environments for malting quality of barley doubled haploids.

Barley doubled haploids covering a wide range of malting quality, along with their parental cultivars and F2, F3 hybrids, were investigated in six environments (three locations, two years) to study the genotype-environment (G x E) interaction structure and the influence of environments on additive, dominance and epistatic gene effects. Grain and malt characters, such as 1000-grain weight, percentage of plump kernels, malt extract yield, protein content, Kolbach index and malt fine-coarse difference (FCD), were measured. Main effects for genetic parameters were estimated and regression analysis was used to explain the interaction of gene effects with environments. The results show that additive effects had the greatest interaction with environments for all the analysed traits, but only for malt characters this interaction was linear. Interaction of dominance effects was much lower and only in the case of 1000-grain weight, protein content and Kolbach index it proved to be significant. The results suggest that effects of heterozygous loci are more stable in contrasting environments than effects of homozygous loci.

Genotype↗

[The expression of API2-MALT1 fusion gene and its influence on the cellular apoptosis and proliferation in gastrointestinal MALT lymphoma].

OBJECTIVE: To investigate the expression of API2-MALT1 fusion gene mRNA and its effect on protein of API2, Caspase3 and Ki67 in gastrointestinal MALT lymphoma (Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue). METHODS: The mRNA of API2-MALT1 fusion transcript was assayed in 33 archival cases of gastrointestinal MALT lymphoma by RT-PCR and nested PCR. According to the expression of API2-MALT1 mRNA or not, 33 cases of MALT lymphoma were divided into two groups. Ki67, API2 and Caspase3 were detected by immunohistochemical technique and analyzed by the microsoft Image-Pro plus. RESULTS: API2-MALT1 fusion gene mRNA was found in 16 of specimens with gastrointestinal MALT lymphoma. The expression rate was 48.4%. The average area (21177.30 +/- 6171.72) micron 2 and single cell average area (29.81 +/- 7.40) micron 2 of API2 were decreased in the group with the expression of API2-MALT1 mRNA, compared with those in the group without the expression of API2-MALT1 mRNA [(34325.65 +/- 6577.00) micron 2, (37.84 +/- 8.55) micron 2]. The integrated optical density(IOD) of API2 showed no significant difference between the two groups, neither did the expression of Ki67 and Caspase3. CONCLUSION: The expression of API2-MALT1 is related to the down-regulated expression of protein of API2, its effect on apoptosis of MALT lymphoma remains to be detected further. The expression of API2-MALT1 mRNA is unrelated to the cellular proliferation.

Apoptosis↗

Early gastric MALT lymphoma.

The endoscopic findings of mucosa-associated lymphoid tissue (MALT) lymphoma were classified into exophytic and infiltrative types by Palmer and Seifert. Normal-appearing gastric MALT lymphoma is quite uncommon, and only one case had been reported in the literature. Here we report the case of a 49-year-old woman who underwent esophagogastroduodenoscopy for health screening. Endoscopy revealed indistinct follicular gastritis mucosal change and a duodenal ulcer scar, and random biopsy was taken from her stomach to check for the presence of Helicobacter pylori (H. pylori). Biopsy revealed chronic gastritis with H. pylori, and atypical lymphoid infiltration highly suggestive of MALT lymphoma. Polymerase chain reaction study using primers specific for immunoglobulin heavy chain gene showed a clonal B cell lymphoproliferation consistent with MALT lymphoma. Treatment with amoxicillin, clarithromycin, and omeprazole for H. pylori rendered complete resolution of the disease. In conclusion, follicular gastritis may be a high-risk condition that gives rise to MALT lymphoma, and further investigation is indicated.

Female↗

Lymphocytic gastritis in Helicobacter pylori-positive gastric MALT lymphoma--report of two cases.

Both lymphocytic gastritis and gastric mucosa associated lymphoid tissue (MALT) lymphoma are associated with Helicobacter pylori (H. pylori) infection. However, this association has not been fully elucidated. We report two cases of lymphocytic gastritis in 57-year-old male and 47-year-old female patients which were diagnosed after the H. pylori eradication to treat gastric MALT lymphoma. MALT lymphoma was successfully treated in case 1, but residual MALT lymphoma remained in case 2. During the follow-up endoscopic examinations, several elevated erosions in case 1 and irregular mucosal atrophy in case 2 were newly detected. Biopsy specimens showed marked infiltration of lymphocytes in the surface epithelium (56.6+/-15.9 intraepithelial lymphocytes (IELs)/100 epithelial cells in case 1 and 40.5+/-9.3 IELs/100 epithelial cells in case 2), which were exclusively CD8-positive T lymphocytes. These findings suggest that H. pylori infection may cause a monoclonal proliferation of B lymphocytes, leading to MALT lymphoma as well as polyclonal proliferation of T lymphocytes which subsequently infiltrated into the surface epithelium as a host immune reaction, resulting in lymphocytic gastritis.

Gastric Mucosa↗

Complete regression of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the gastric stump after eradication of Helicobacter pylori.

Recent studies have suggested that Helicobacter pylori (H. pylori)-associated gastritis may play an important role in the pathogenesis of primary gastric lymphoma. Recently, triple therapy using proton pump inhibitor, amoxicillin, and clarithromycin, has been established for the eradication therapy of H. pylori infection, and is also recommended for the treatment of the superficial type of low-grade gastric MALT (mucosa-associated lymphoid tissue ) lymphoma. MALT lymphoma of the gastric stump is rare, and total resection or chemotherapy for MALT lymphoma of the gastric stump has been previously reported. Therefore, there is no evidence that eradication therapy is effective for low-grade MALT lymphoma of the gastric stump. Our case illustrates the remarkable efficacy of eradication of H. pylori for low-grade MALT lymphoma of the gastric stump without other modalities such as surgery and systemic chemotherapy.

Aged↗

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT-type) require CD40-mediated signaling and Th2-type cytokines for in vitro growth and differentiation.

To investigate the mechanisms of T cell dependence underlying the development of extranodal mucosa-associated lymphoid tissue (MALT)-type B cell lymphomas, the activation, proliferation, and differentiation of lymphoma B cells were studied using ligand binding to the CD40 membrane receptor. The activation and proliferative response of all investigated low-grade MALT-type lymphomas (n = 6) was strongly dependent on anti-CD40-mediated signals and was complemented by cytokines produced by T helper cells of the Th2 type (interleukin-4 (IL-4) and/or IL-10). Th1 cytokines (IL-2 and/or interferon-gamma) bad little effect. Low-grade, but less so high-grade, MALT-type lymphoma B cells were induced to secrete large amounts of tumor immunoglobulin in response to IL-10. In contrast, high-grade MALT-type lymphomas (n = 5) proliferated in response to both Th2- and Th1-type cytokines and CD40 stimulation, whereas Burkitt lymphomas (n = 3) could not be rescued from apoptosis by CD40 stimulation with or without cytokines. These results suggest that CD40 signaling in combination with Th2 cytokines are essential for the development and progression of low-grade MALT-type B cell lymphoma. We conclude that T cells, which activate B cells in a CD40-dependent fashion, may contribute to lymphoma pathogenesis.

B-Lymphocyte Subsets↗

Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone.

The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.

Adult↗

Gastric MALT lymphoma and Helicobacter pylori.

The majority of low grade gastric lymphomas arise within acquired organized lymphoid tissue, which has all the features of MALT. This MALT is specifically acquired most commonly in response to infection of the gastric mucosa by H pylori. The lymphocytes within this MALT are therefore programmed to respond to this organism and the neoplastic cells of the lymphoma that may develop within this acquired MALT retain the ability to respond to the immunological proliferative drive associated with the continued presence of the organism. Following the removal of this immunological drive by eradication of the organism in vivo, the lymphoma shows clinical and histological regression. The time required to see this response is unknown and there are some lymphomas that fail to respond to simple Helicobacter eradication. In some cases, there is continued molecular evidence of the presence of the lymphoma clone in low levels and the significance of this remains unknown. These factors are presently under detailed examination, and several clinical trials to assess the response of a large series of low grade gastric MALT lymphomas to anti-Helicobacter therapy and the requirement for additional chemotherapy are at present in progress.

Gastric Mucosa↗

Thyroid MALT lymphoma in patients with a compressive goiter.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas account for less than 1% of all primary thyroid malignancies. They typically arise as neoplastic transformations within areas of autoimmune thyroiditis. Although they tend to have an indolent course, these lymphomas present a diagnostic challenge requiring a high level of suspicion in patients at increased risk of development. METHODS: We retrospectively reviewed 3 cases of primary MALT thyroid lymphoma discovered in patients with a compressive goiter. This represents the experience at a single institution from 1996 to 2005. Hospital and clinic records were reviewed to identify the workup, treatment, and outcome. RESULTS: One of 3 patients underwent preoperative fine-needle aspiration (FNA). All patients underwent total thyroidectomy to relieve compressive symptoms, and the final pathology revealed MALT lymphoma. Two patients subsequently underwent radiation therapy. All patients are alive without evidence of disease recurrence. CONCLUSIONS: These cases are notable for the unexpected presentation of MALT lymphoma within a compressive goiter.

Adult↗

CRP induces the repositioning of MalT at the Escherichia coli malKp promoter primarily through DNA bending.

Activation of transcription initiation at the Escherichia coli malKp promoter requires the repositioning of MalT, the primary activator, from a set of non-productive sites to a set of productive sites, which is staggered by 3 bp. Occupation of the latter relies on the formation of a higher order structure involving distal MalT sites and the binding of CRP (cAMP receptor protein) to three sites located in the intervening region. We show here that one can successfully replace all of the CRP sites by the binding site of another DNA-bending protein, integration host factor, or by a sequence-directed bend without altering the process of malKp activation. This observation indicates that CRP action at malKp does not involve critical interactions with MalT and that CRP promotes MalT repositioning primarily through DNA bending. This structural role of CRP differs markedly from its role in the activation of the lac promoter.

Bacterial Proteins↗

Sonographic detection of secondary MALT lymphoma of the submandibular gland.

This report describes a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the lacrimal glands that recurred in the submandibular salivary glands. Gray-scale sonography showed small hypoechoic nodules, measuring less than 0.5 cm in diameter, in both submandibular glands. The echogenicity and echotexture of the rest of the submandibular glands and of the parotid glands was normal. Power Doppler sonography revealed increased vascularity within the nodules. A sonographically guided aspiration biopsy of the nodules revealed MALT lymphoma. Secondary MALT lymphoma should be considered in the presence of multiple small hypoechoic nodules in the salivary glands in patients with a history of MALT lymphoma at another location.

Female↗

Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma in an animal model of 'Helicobacter heilmannii' infection.

While Helicobacter pylori is accepted as the dominant human gastric bacterial pathogen, a small percentage of human infections have been associated with another organism, commonly referred to as 'Helicobacter heilmannii', which is more prevalent in a range of animal species. This latter bacterium has been seen in association with the full spectrum of human gastric diseases including gastritis, peptic ulceration, and gastric carcinomas, including gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study describes an analysis of the pathogenic potential of a number of 'H heilmannii' isolates in an animal model of gastric MALT lymphoma. BALB/c mice were infected with ten different 'H heilmannii' isolates originating from both human and animal hosts. The animals were examined at various time points for up to 28 months after infection. The infected animals initially developed a chronic inflammatory response within 6 months. This histological response increased in severity with the length of infection, with the development of overt lymphoma in some animals 18 months after infection. MALT lymphomas were detected in up to 25% of the infected animals. The prevalence of lymphoma was dependent on the length of infection and the origin of the infecting isolates. A range of other histological features accompanied the lymphocytic infiltration, including invaginations of the gastric epithelium and associated hyperplastic tissue, mucus metaplasia, and a small number of diffuse large B-cell lymphomas. The ability to manipulate experientially the presence of the bacterium in the animal model will allow further studies examining the role of antigen drive in the development of Helicobacter-associated MALT lymphoma.

Animals↗

Two-dimensional gel electrophoresis pattern (pH 6-11) and identification of water-soluble barley seed and malt proteins by mass spectrometry.

A protocol was established for two-dimensional gel electrophoresis (2-DE) of barley seed and malt proteins in the pH range of 6-11. Proteins extracted from flour in a low-salt buffer were focused after cup-loading onto IPG strips. Successful separation in the second dimension was achieved using gradient gels in a horizontal SDS-PAGE system. Silver staining of gels visualized around 380 (seed) and 500 (malt) spots. Thirty-seven different proteins from seeds were identified in 60 spots, among these 46 were visualized also in the malt 2-D pattern. Proteins were identified by peptide mass fingerprinting and by tandem MS sequencing after in-gel digestion by trypsin. In addition, the N-terminal sequence of 10 different proteins from 11 spots was determined after electroblotting to a polyvinylidene difluoride (PVDF) membrane. Five identified proteins (in 9 spots) are involved in glycolysis, 12 in defence against pathogens (21 spots), 4 in storage, folding, and synthesis of proteins, and in nitrogen metabolism (5 spots), 6 in carbohydrate metabolism (11 spots), and 4 in stress and detoxification (9 spots). Six proteins (7 spots) were not grouped in these categories, and 3 were not ascribed a function. The presented 2-D patterns and identifications will be used to describe proteome differences between cultivars and changes during malting.

Carbohydrates↗

Probing heat-stable water-soluble proteins from barley to malt and beer.

Proteins determine the quality of barley in malting and brewing end-uses. In this regard, water-soluble barley proteins play a major role in the formation, stability, and texture of head foams. Our objective was to survey the barley seed proteins that could be involved in the foaming properties of beer. Therefore, two-dimensional (2-D) electrophoresis and mass spectrometry were combined to highlight the barley proteins that could resist the heating treatments occurring during malting and brewing processes. As expected, from barley to malt and to beer, most of the heat-stable proteins are disulfide-rich proteins, implicated in the defense of plants against their bio-aggressors, e.g., serpin-like chymotrypsin inhibitors (protein Z), amylase and amylase-protease inhibitors, and lipid transfer proteins (LTP1 and LTP2). For LTP1s, the complex pattern displayed in 2-D electrophoresis could be related to some chemical modifications already described elsewhere, such as acylation or glycation through Maillard reactions, which occur on malting. Our proteomics approach allowed the identification of the numerous proteins present in beer in addition to the major ones already described. The involvement of these proteins in the quality of beer foam can now be evaluated.

Beer↗

Role of activated host T cells in the promotion of MALT lymphoma growth.

Gastric mucosa-associated lymphoid tissue (MALT) B cell lymphomas contain activated helper T cells. The evidence supports the presence of mechanisms of T cell dependence underlying the development of these lymphomas. It appears that the T cells, which activate B cells, may contribute to lymphoma pathogenesis. Co-stimulatory molecules necessary for effective B cell/T cell interaction are expressed in MALT lymphomas. The studies suggest that CD40 signaling, in combination with cytokines, is essential for the development and progression of MALT lymphomas. Activated T cells of low grade gastric MALT lymphoma, while delivering full help to B cells, are apparently deficient in two cytotoxic mechanisms involved in the concomitant control of B cell growth.

Cytotoxicity, Immunologic↗

Epidemiological and prognostic aspects of gastric MALT-lymphoma.

Since mucosa-associated lymphoid tissue (MALT) lymphoma was defined in the mid-1980s as a clinicopathologic entity, many sets of data on pathological, biological and clinical aspects have been generated. In particular, the finding that this process was responding well to antibiotic treatment fueled interest in it and has led to several clinical trials. This overview deals with epidemiological and prognostic aspects and identifies important questions which need to be answered before data from different sources can be compared. Incidence figures of gastric MALT lymphoma vary between countries and parallel the numbers of all non-Hodgkin's lymphoma. The incidence does not parallel the occurrence data of Helicobacter pylori infection. Incidence figures are highly dependent on the definition used for MALT-type primary gastric lymphomas. Several studies show that some prognostic factors are relevant, for instance stage and grade, whereas other factors such as the International Prognostic Index or treatment are not. These studies do not include the recently introduced antibiotic therapy. The inclusion of recent insights in biology and the treatment of gastric MALT lymphomas in prospective clinical studies will soon answer some of the main questions posed.

Aged↗

Physical and genetic structure of the glpD-malT interval of the Escherichia coli K-12 chromosome. Identification of two new structural genes of the glp-regulon.

A transducing lambda phage carrying glpD''lacZ, glpR, and malT was isolated from a strain harboring a glpD''lacZ fusion. Comparison of restriction endonuclease cleavage patterns of DNA isolated from this phage with that of the previously cloned malT region (Raibaud and Schwartz 1980) facilitated the construction of recombinant plasmids carrying different portions of the glpD-malT region. Results of minicell analysis and complementation studies showed that this region of the chromosome encodes at least five polypeptides. These included the previously identified glpD, glpR, and malT gene products. In addition, two new structural genes of the glp regulon (glpE and glpG) located between the glpD and glpR genes were identified. Hybrid plasmids carrying glpD''lacZ and glpR''lacZ fusions were constructed. Restriction endonuclease cleavage analysis of these two plasmids demonstrated that glpD and glpR are divergently transcribed.

Bacteriophage lambda↗