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E O Riecken

Publications and source records attributed to E O Riecken.

At least 19 recordsLinked to original sources
PubMed2005

[Definitions of celiac disease--statement of an expert group from the German Society for Celiac Disease].

Celiac disease may have different manifestations and the clinical course can be very heterogeneous. Thus, management and treatment of celiac disease can be difficult and therefore requires individual patient care. In this article an expert group from the German Society for Celiac Disease (Deutsche Zöliakie-Gesellschaft) defines the different manifestations of celiac disease. In the past these definitions were often used differently. The consequent usage of these definitions may diminish uncertainties in clinical practice and lead to a more standardized management of the disease which is likely to improve patient care.

Adult↗
PubMed2002

Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells.

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a new treatment modality for early esophageal neoplasia. With two absorption maxima in the visible light range (550 and 588 nm) hypericin is a very promising photosensitizer for PDT with incoherent light sources. We studied the effects of photosensitizing hypericin in both primary cell cultures and cell lines (squamous: Kyse-140 and adenocarcinoma: OE-33) of human esophageal cancer using an incoherent white light source. MATERIALS AND METHODS: Esophageal cancer cells were preincubated (4-24 h) with hypericin (10 nM-1 micro M) and then irradiated with a light energy dose of 30 J/cm(2). RESULTS: Hypericin showed strong phototoxic effects and induced apoptosis in a dose-dependent fashion. The IC(50) value of hypericin phototoxicity was approximately 30 nM in both squamous and adenocarcinoma cells. In the concentrations used nonphotoactivated hypericin showed no toxic or apoptotic potency. The phototoxicity of hypericin was compared to that of delta-aminolevulinic acid (5-ALA), which is already being used for photodynamic therapy of gastrointestinal cancer. 5-ALA produced similar phototoxic effects but at a much higher dose (IC(50) 182+/-8 micro M in Kyse-140 and 308+/-40 micro M in OE-33 cells). Moreover, 5-ALA did not induce apoptosis to a relevant extent. CONCLUSION: Hypericin is a very promising new photosensitizer for innovative photodynamic therapy of esophageal cancer. Both the well known clinical safety of hypericin and the lower costs of broad band light sources argue in favor of clinical trials.

Adenocarcinoma↗
PubMed2002

Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells.

C-11- or F-18-DOPA positron emission tomography (DOPA PET) is a new sensitive imaging technique for small neuroendocrine gastrointestinal tumors which evaluates the decarboxylase activity. To further characterize the dopaminergic system in neuroendocrine gastrointestinal tumor cells, we investigated the expression of both dopamine receptors and the transmembrane dopamine transporter (DAT) in the human neuroendocrine pancreatic cell line BON and in the neuroendocrine gut cell line STC-1. Both BON and STC-1 cells expressed mRNA of the dopamine receptors D2-D5 and DAT. mRNA of the dopamine receptor D1 was detected in BON cells only. Both in BON and STC-1 cells, expression of D2 and D5 receptors and DAT was also demonstrated immunocytochemically. For functional receptor characterization intracellular cAMP levels ([cAMP]i) were determined. Whereas in STC-1 cells dopamine and the D1-like (D1/D5) receptor agonist SKF 38393 increased [cAMP]i, [cAMP]i was decreased by dopamine or the D2-like (D2-D4) receptor agonist quinpirole in BON cells. Functional DAT activity was, however, not detected in either cell line. The presence of both dopamine receptors and of the DAT suggests an autocrine and/or paracrine function of dopamine in neuroendocrine gastrointestinal tumor cells. Yet neither the transmembrane dopamine transporter nor dopamine receptors are likely to contribute to positive DOPA PET imaging of neuroendocrine gastrointestinal tumors. However, these molecules may be of diagnostic importance when applying other dopaminergic system tracers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells.

The peripheral benzodiazepine receptor (PBR) has been implicated in growth control of various tumour models. Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorectal cancers and the human colorectal carcinoma cell lines HT29, LS174T, and Colo320 DM we studied the involvement of PBR in the growth control and apoptosis of colorectal cancers. Both mRNA and protein expression of PBR were detected by RT-PCR and flow cytometry. Using confocal laser scanning microscopy and immunohistochemistry the PBR was localized in the mitochondria. The specific PBR ligands FGIN-1-27, PK 11195, or Ro5-4864 inhibited cell proliferation dose-dependently. FGIN-1-27 decreased the mitochondrial membrane potential, which indicates an early event in apoptosis. Furthermore, FGIN-1-27, PK 11195 or Ro5-4864 increased caspase-3 activity. In addition to their apoptosis-inducing effects, PBR ligands induced cell cycle arrest in the G(1)/G(0)-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer.

Adult↗
PubMed2001

Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.

Collagen type XVIII (C18) is a nonfibrillar collagen of basement membranes. Its C-terminal fragment, endostatin, has been identified as an inhibitor of angiogenesis. C18 is predominantly expressed by hepatocytes of normal, cirrhotic and neoplastic liver. We compared the patterns of C18 RNA-expression in colonic adenocarcinoma metastases, which represent the most frequently occurring liver tumours, to normal colon mucosa, to primary colon cancers and to ovarian cancers which are often morphologically similar to colonic cancer or metastasis. Two C18-specific RNA-probes were generated to perform in situ hybridization combined with immunohistochemistry for cytokeratin, vimentin and the endothelial marker CD31, in order to characterize the C18-expressing cells. C18/endostatin protein was localized by immunohistology. In colorectal carcinomas and their liver metastases high levels of C18 transcripts were observed in endothelial cells and fibroblasts/myofibroblasts, whereas C18 RNA was virtually absent from carcinoma cells. Ovarian carcinomas displayed high C18 RNA expression both in carcinoma and stromal cells, indicating that induction of C18 transcription in tumour stromal cells is independent of the ability of carcinoma cells to express C18. While the role of tumour cell derived C18 in cancer growth regulation remains unknown, stimulation of proteolysis of the locally strongly expressed C18 to endostatin could offer an attractive approach for a targeted antineoplastic therapy.

Adenocarcinoma↗
PubMed2001

Interstitial collagens I, III, and VI sequester and modulate the multifunctional cytokine oncostatin M.

The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that oncostatin M (OSM), a profibrogenic cytokine and modulator of cancer cell proliferation, specifically binds to collagen types I, III, IV, and VI, immobilized on polystyrene or nitrocellulose. Single collagen chains inhibit these interactions in a dose-dependent manner. Cross-inhibition experiments of collagen-derived peptides point to a limited set of OSM-binding collagenous consensus sequences. Furthermore, this interaction is found for OSM but not for other interleukin-6 type cytokines. OSM binding to collagens is saturable, with dissociation constants around 10(-8) m and estimated molar ratios of 1-3 molecules of OSM bound to one molecule of triple helical collagen. Furthermore, collagen-bound OSM is biologically active and able to inhibit proliferation of A375 melanoma cells. We conclude that abundant interstitial collagens dictate the spatial pattern of bioavailable OSM. This interaction could be exploited for devising collagenous peptide-antagonists that modulate OSM bioactivity in tumor growth and fibrotic disorders like rheumatoid arthritis and hepatic fibrosis.

Binding Sites↗
PubMed2001

Regulation of the intestinal mucin MUC2 gene expression in vivo: evidence for the role of promoter methylation.

In the present work we investigated the in vivo regulation of the mucin gene MUC2, which is overexpressed in all mucinous colorectal carcinomas. The inhibition of methylation by 5-azadeoxycytidine induces de novo expression of MUC2 in the colon carcinoma cell line COLO 205. The expression is retained in xenograft tissue and the cells give rise to MUC2-expressing tumours in nude mice. The strong expression of MUC2 in the normal human goblet cells and in the tissue of human mucinous colorectal carcinomas is associated with the average methylation of about 50% at every investigated CpG site of the MUC2 promoter. In contrast, MUC2 promoter in the non-expressing normal columnar cells and in the non-mucinous carcinoma tissue is methylated to nearly 100%. These data show that (i) low methylation of MUC2 promoter is associated with MUC2 expression in vivo and (ii) the pattern of MUC2 promoter methylation in the normal goblet or columnar cells most closely resembles that in mucinous or non-mucinous colorectal carcinomas, respectively. They indicate that MUC2 expression in vivo is regulated by promoter methylation and support the hypothesis that cells with goblet-like differentiation give rise to mucinous colonic carcinomas.

Animals↗
PubMed2001

Growth inhibition and apoptosis induced by P2Y2 receptors in human colorectal carcinoma cells: involvement of intracellular calcium and cyclic adenosine monophosphate.

Extracellular nucleotides induce apoptosis and inhibit growth of colorectal cancer cells. To understand the underlying signaling pathways, we investigated the role of nucleotide-sensitive P2 receptors and focused on the receptor-mediated signaling of intracellular Ca2+ and cyclic adenosine monophosphate (cAMP) in two colorectal carcinoma cell lines (HT29, Colo320 DM). Expression and functionality of P2 receptor subtypes evaluated by RT-PCR and [Ca2+]i imaging revealed that solely metabotropic P2 receptors of the subtype P2Y2 were expressed on a functional level in both cell lines. Short-term stimulation of P2Y2 receptors caused Ca2+ mobilization from intracellular stores and a subsequent transmembrane Ca2+ influx. The receptor-induced [Ca2+]i elevation was shown to increase basal-stimulated [cAMP]i moderately and to potentiate forskolin-stimulated [cAMP]i vigorously, since the effects were dose-dependently inhibited by preloading the cells with the [Ca2+]i chelator BAPTA. In contrast, activation of protein kinase C (PKC) did not contribute to a receptor-mediated rise in [cAMP]i, since the PKC inhibitor staurosporine completely failed to reduce P2Y2 receptor-induced increases in [cAMP]i. Prolonged application of P2Y2 receptor agonists induced a time-dependent increase in apoptosis (up to 50% above control values) in both cell lines and caused dose-dependent inhibition of cell proliferation of up to 85% (Colo320 DM) or 64% (HT29). Chelating [Ca2+]i with BAPTA almost completely abolished P2Y2 receptor-induced cell death. Rises in [cAMP]i elicited by either forskolin or cAMP derivatives inhibited growth in both cell lines, too. In line with the potentiating effect of P2Y2 receptors on forskolin-stimulated [cAMP]i increases, costimulation with forskolin and P2Y2 receptor agonists led to synergistic antiproliferative effects. Moreover, a synergistic growth inhibition was observed when coincubating the cells with the P2Y2 receptor agonist ATP and the cytostatic drug 5-fluorouracil, which forms the basis for most currently applied chemotherapeutic regimes in colorectal cancer treatment. Our results demonstrate the growth inhibitory potency of P2Y2 receptors in colorectal carcinoma cells. Receptor-induced [Ca2+]i signaling appears to play a major role in the observed antiproliferative and apoptosis-inducing effects.

Adenosine Triphosphate↗
PubMed2001

Modulation of collagen XVIII/endostatin expression in lobular and biliary rat liver fibrogenesis.

BACKGROUND/AIMS: The liver is the major source of collagen XVIII (C18), the precursor of the angiogenesis inhibitor endostatin. In human liver C18 is mainly expressed by hepatocytes. However, its quantitative and temporospatial expression patterns during liver fibrogenesis are unknown. METHODS: We used RNA quantification and in situ hybridization combined with cell-specific markers to study C18 compared to procollagen alpha1(I) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA expression in acute (single dose of CCl4) and chronic (biliary) rat liver fibrogenesis. RESULTS: C18 transcripts were only found in hepatocytes and bile duct epithelia of normal and fibrotic livers, and occasionally in arterial myocytes and hepatic stellate cells. 72 h after CCl4 injection, C18 mRNA levels remained unchanged, while procollagen alpha1(I) mRNA was increased at 72 h and TIMP-1 mRNA peaked at 12 h (P < 0.05). In biliary fibrosis C18 mRNA levels increased 1.8-fold, contrasting with 20- and 4-fold elevated procollagen alpha1(I) and TIMP-1 transcript levels, respectively. CONCLUSIONS: Hepatocytes and bile duct epithelia are the predominant sources of C18 in normal and fibrotic rat liver. Contrary to procollagen alpha1(I) and TIMP-1, C18 expression remains constant in acute fibrogenesis and is upregulated in biliary fibrosis. Modulation of epithelial C18 expression and its processing to endostatin could allow a liver-specific anticancer therapy.

Animals↗
PubMed2001

Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen alpha1(I) and TIMP-1.

BACKGROUND/AIMS: Silymarin reduces hepatic collagen accumulation by 35% in rats with secondary biliary cirrhosis. The aim of the present study was to explore its antifibrotic mechanism. METHODS: Thirty female adult Wistar rats were allocated to (1) bile duct occlusion, (2) bile duct occlusion and oral silymarin at 50 mg/kg per day, and (3) sham operation and oral silymarin at 50 mg/kg per day. Steady-state mRNA levels for procollagen alpha1(I), tissue inhibitor of metalloproteinases-1 (TIMP-1), and transforming growth factor (TGF) beta1 were determined by multi-probe ribonuclease protection assay. RESULTS: After 6 weeks of bile duct occlusion, liver collagen content was increased 12-fold, when compared with the sham-operated controls. These animals displayed 17-, 6.5- and 16-fold higher transcript levels for procollagen alpha1(I), TIMP-1 and TGFbeta1 (P < 0.01). Silymarin downregulated elevated procollagen alpha1(I), TIMP-1 and TGFbeta1 mRNA levels by 40-60% (P < 0.01). These lowered hepatic profibrogenic transcript levels correlated with decreased serum levels of the aminoterminal propeptide of procollagen type III. CONCLUSIONS: Silymarin suppresses expression of profibrogenic procollagen alpha1(I) and TIMP-1 most likely via downregulation of TGFbeta1 mRNA in rats with biliary fibrosis. The serum procollagen type III propeptide level mirrors profibrogenic mRNA expression in the liver.

Animals↗
PubMed2001

Rapid increase of mucosal CD4 T cells followed by clearance of intestinal cryptosporidiosis in an AIDS patient receiving highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) suppresses the replication of human immunodeficiency virus (HIV) and leads to an increase in circulating CD4 T lymphocytes, but its effects on other immune compartments such as the intestinal mucosa are not well understood. We describe a severely immunodeficient HIV-infected patient with intractable watery diarrhea and weight loss caused by infection with Cryptosporidium parvum in whom we studied virologic and immunologic changes in both peripheral blood and the intestinal mucosa after initiating HAART. Mucosal biopsies were performed by rectoscopy before and at several time points after HAART was begun. Nucleic acids were extracted from rectal biopsy specimens and blood samples, and HIV RNA was measured by reverse-transcription polymerase chain reaction. Lymphocytes were isolated from rectal biopsy specimens after mechanical disaggregation, and circulating and mucosal CD4 T cells were determined by flow cytometry. HAART led to clinical recovery and eradication of cryptosporidiosis. In both blood and mucosa, HIV RNA decreased below the limit of detection and CD4 T cells increased. Mucosal CD4 T cells increased much faster and to much higher levels than circulating CD4 T cells. Our findings show a rapid repopulation of the intestinal mucosa with CD4 T cells after initiation of HAART that can effectively restore mucosal immunity, leading to eradication of opportunistic pathogens.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome.

BACKGROUND & AIMS: Abdominal symptoms in the absence of mucosal abnormalities are features of both the irritable bowel syndrome (IBS) and latent/potential celiac disease (cd). To identify a possible subgroup of IBS patients with latent/potential cd, surrogate markers of cd were investigated in IBS patients. METHODS: IBS patients suffering from diarrhea (n = 102), and patients with active cd (n = 10), treated cd (n = 26), and latent cd (n = 5) were included in the study. We measured serum immunoglobulin (Ig) A against gliadin and tissue-transglutaminase, and IgA and IgM against gliadin, tissue-transglutaminase (intestinal cd-associated antibodies), and the dietary proteins beta-lactoglobulin and ovalbumin in duodenal aspirate by enzyme-linked immunosorbent assay. Intraepithelial lymphocytes (IELs) were counted in histology sections, and the expression of HLA-DQ2 (A1*0501/B1*0201) was investigated by polymerase chain reaction. In 26 IBS patients, the effect of 6 months of gluten withdrawal was examined. RESULTS: Most cd patients expressed HLA-DQ2 and had increased intestinal cd-associated antibodies, whereas cd-associated serum IgA and IEL counts were increased in active cd in contrast to treated or latent cd. In IBS patients, 35% were HLA-DQ2-positive, 23% had increased IEL counts, and 0% and 30% had increased cd-associated antibodies in serum and duodenal aspirate, respectively. Furthermore, stool frequency and intestinal IgA decreased significantly under a gluten-free diet in the subgroups of HLA-DQ2-positive and intestinal antibody-positive IBS patients when compared with IBS patients without these markers. CONCLUSIONS: HLA-DQ2 expression and increased intestinal cd-associated antibodies are markers that can identify latent/potential cd in a subgroup of IBS patients who consequently appear to profit from a gluten-free diet.

Adolescent↗
PubMed2001

Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance.

BACKGROUND: The mechanism of the antisecretory effect of loperamide was investigated in cultured highly differentiated colon epithelial cells (HT-29/B6). METHODS: Chloride secretion was stimulated via cAMP by forskolin (FSK, 10(-5) M), via Ca2+ by the muscarinic agonist carbachol (CCh, 10(-4) M), and via protein kinase C by the phorbol ester PMA (5 x 10(-9) M). Stimulated Cl- secretion was quantified as short circuit current (I(SC)) of HT-29/B6 monolayers mounted in Ussing-type chambers. RESULTS: Loperamide (5 x 10(-5) M) inhibited I(SC) stimulated by FSK, CCh and PMA. The antisecretory action of loperamide was unaffected by preincubation with naloxone (10(-5) M). Furthermore, loperamide strongly inhibited basolateral 86Rb efflux. Like loperamide, the calmodulin antagonist trifluoperazine (10(-4) M) inhibited I(SC) induced by FSK, CCh or PMA. The Ca2+ channel blocker verapamil (5 x 10(-5) M), on the other hand, inhibited only PMA-stimulated I(SC),but had no effect on FSK or CCh-induced I(SC) CONCLUSIONS: Loperamide exerts a direct antisecretory action on chloride secretion of colon epithelial cells independently of the respective stimulatory signal transduction pathway. This antisecretory effect is not mediated by opiate receptors and reflects inhibition of basolateral K+ conductance.

Antidiarrheals↗
PubMed2001

Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer.

OBJECTIVE: To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. METHODS: The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months' survival for combined groups 0 and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III-IV colorectal cancer.

Adenocarcinoma↗
PubMed2001

Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T cell lymphoma, coeliac disease, and refractory sprue.

BACKGROUND: Clonal T cell receptor (TCR) gene rearrangements and loss of T cell antigens such as CD8 and TCR-beta in intraepithelial lymphocytes (IELs) may indicate the development of an enteropathy-type intestinal T cell lymphoma (EITCL) in patients with refractory sprue. AIMS: To define the diagnostic value of these markers in duodenal biopsies from patients with villous atrophy as a result of various underlying disorders. PATIENTS AND METHODS: Duodenal biopsies from eight patients with coeliac disease and five patients with villous atrophy caused by defined disorders were compared with three patients with refractory sprue evolving into overt EITCL, two patients with ulcerative jejunitis, and with eight patients with overt EITCL, for expression of CD3, CD4, CD8, and TCR-beta in IELs using immunohistochemistry and for clonal TCR-gamma gene rearrangements using polymerase chain reaction. In addition, biopsies from six consecutive patients with refractory sprue of uncertain cause were examined. RESULTS: Clonal TCR-gamma gene rearrangements were found in all resected tumours of patients with EITCL, in 3/8 duodenal biopsies of patients with EITCL, in 2/2 patients with ulcerative jejunitis, in 2/3 patients with refractory sprue evolving into overt EITCL, and in 1/6 patients with refractory sprue. No rearrangements were found in biopsies from patients with refractory sprue caused by defined disorders or those with coeliac disease. Clonality in duodenal biopsies was associated with an abnormal phenotype of IELs in all cases and in all but one case in patients with evidence of underlying coeliac disease. Specificity for detection of an EITCL using immunohistology was 77% for CD8 and for TCR-beta staining, and 100% for detection of a clonal TCR-gamma gene rearrangement. Sensitivity was 62% for staining with CD8 and clonality investigation, while sensitivity reached 100% for TCR-beta staining in all investigated patients with EITCL. CONCLUSIONS: Clonal proliferations of phenotypically abnormal IELs in refractory sprue represent an early manifestation of EITCL, for which the term "sprue-like intestinal T cell lymphoma" is proposed. This constellation is also found in duodenal biopsies from patients with an overt EITCL and is not related to other sprue syndromes, resulting in a high specificity for detection of an EITCL or refractory sprue evolving into EITCL. Overt EITCL may develop directly from coeliac disease without a precursor lesion (refractory sprue with clonal IELs) being demonstrable in duodenal biopsies or via a "sprue-like intestinal T cell lymphoma". This latter entity is a complication of coeliac disease.

Adolescent↗
PubMed2000

Collagens serve as an extracellular store of bioactive interleukin 2.

The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that interleukin 2 (IL-2), an important stimulator of T cell growth, preferentially binds to collagen types I, III, and VI and to a lesser degree to collagen types II, IV, and V, immobilized on polystyrene or nitrocellulose. These interactions are inhibited by denatured, single collagen chains or a subset of their cyanogen bromide peptides in a dose-dependent manner. Cross-inhibition experiments and ligand blotting of collagen-derived peptides point to a limited set of collagenous consensus sequences mediating the binding of IL-2. This interaction is saturable, with dissociation constants of approximately 10(-)(8) m, and estimated molar ratios of 4-6 molecules of IL-2 bound to one molecule of triple helical collagen. Furthermore, collagen-bound IL-2 stimulates proliferation of mouse lymphocytes. We conclude that its specific binding to the abundant interstitial collagens leads to a spatial pattern of bioavailable IL-2 which is dictated by the local organization of the collagenous extracellular matrix. This interaction may contribute to the particular phenotype of stromal lymphocytes and could be exploited for devising collagenous peptide analogues that modulate IL-2 bioactivity.

Animals↗
PubMed2000

Expression of SIALYL-Le(x) antigen defined by MAb AM-3 is an independent prognostic marker in colorectal carcinoma patients.

Expression of mucin-bound sialyl-Le(x) antigen during the progression of colorectal carcinoma and its potential prognostic value were analysed in sections of tumours from 182 patients with a documented follow-up by immunohistochemistry using the monoclonal antibody (MAb) AM-3. Two groups of colonic carcinomas with weak (n = 79) and strong (n = 103) sialyl-Le(x) expression were discerned. The percentage of strongly expressing tumours increased with the progression of the disease (UICC stage I = 10%, stage II = 46%, stage III = 63%, stage IV = 68%, p < 0.0001). Seventy-four percent of patients with carcinomas exhibiting a strong sialyl-Le(x) expression but only 34% of patients with weak sialyl-Le(x) expression died of the disease (p = 0.0026). In multivariate analysis, strong sialyl-Le(x) expression increased the relative risk of cancer-related death 3.8-fold (95% CI = 1.8-7.9, p = 0.00034). The separate analyses of patients in UICC stage II (n = 56), III (n =5 9) and IV (n = 57) revealed that strong sialyl-Le(x) expression was associated with a reduction of the 5-year overall survival rate in UICC stage II (84% vs. 54%, p = 0.0013) and in stage III patients (86% vs. 35%, p = 0.0008) after curative resection but was not relevant in patients with distant metastases. In conclusion, the strong expression of sialyl-Le(x) antigen defined by the MAb AM-3 in colorectal carcinomas is an independent unfavourable prognostic factor after curative resection in stage II and III patients. The predictive power of the sialyl-Le(x) expression may be helpful to define subgroups of patients at high risk for whom preventive adjuvant therapy can be selectively applied before the occurrence of detectable metastases.

Adult↗