Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brush border of normal small-intestine epithelial cells is rich in enzymes that are involved in the digestive process. Such molecules can be used as markers to analyze cell lineages and differentiation properties of colorectal cancers. Monoclonal antibodies detecting dipeptidyl peptidase-IV, aminopeptidase N, endopeptidase F, sucrase-isomaltase, alkaline phosphatase, maltase-glucoamylase and lactase have been used to analyze the phenotype of colorectal cancers, adjacent mucosa and histologically normal distant mucosa. The avidin-biotin peroxidase complex method was used. Expression of dipeptidyl peptidase-IV, aminopeptidase N, sucrase-isomaltase and alkaline phosphatase was common in non-neoplastic mucosa adjacent to, and distant from, the tumor; in contrast, endopeptidase F, maltase-glucoamylase and lactase were rarely expressed in normal distant mucosa and more frequently expressed in mucosa adjacent to the tumor. Dipeptidyl peptidase-IV, aminopeptidase N, endopeptidase F, sucrase-isomaltase and alkaline phosphatase were frequently expressed in colorectal cancers, whereas maltase-glucoamylase and lactase were rarely expressed. Two general patterns of antibody reactivity were observed: diffuse cytoplasmic and apical; apical reactivity was generally associated with more differentiated tumors. A logistic predictive regression model indicated that enzyme expression in colorectal cancers followed a coordinate pattern, but was unrelated to the location of the tumor, Dukes stage or differentiation grade. In conclusion, expression of brush-border-associated enzymes occurs frequently in colorectal cancers and is regulated in a co-ordinated manner. These markers can be used for the phenotypic sub-classification of colorectal cancers.
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PMID:Intestinal brush-border-associated enzymes: co-ordinated expression in colorectal cancer. 134 6

Expression and cellular localization of brush-border enzymes (aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase) in normal human colon, colonic polyps and malignant intestinal tumors were investigated with a panel of monoclonal antibodies reacting with either native or denatured proteins. The enzymes were detected on cryostat sections by indirect immunofluorescence staining, or affinity-purified and analyzed by gel electrophoresis and immunoblotting. Dipeptidylpeptidase IV, lactase and maltase were absent from all samples examined, while aminopeptidase N (APN) was detected at the basal membrane of the epithelial cells in most specimens of colon obtained from individuals free of intestinal tumors. In contrast, APN was frequently localized at the luminal membrane of the surface epithelium in large-intestinal mucosa distal to tumors, adenomas and hyperplastic polyps, and from members of hereditary colon cancer syndrome families. APN was also expressed in colonic tumors, where it was present in an apical cell membrane location in 3/23 adenomas and 14/35 adenocarcinomas examined. No correlation was found between tumor-cell invasiveness (classified by "Dukes" stage) and expression or cellular location of aminopeptidase N. Histologically, all positive tumors were moderately or well differentiated. These results suggest that aminopeptidase N is normally expressed in adult human colon, but epithelial cells in the large and small intestine differ in their ways of sorting this enzyme intracellularly and eventually inserting it into different aspects of their surface membrane, a process which may be altered at an early stage of carcinogenesis.
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PMID:Expression and different polarity of aminopeptidase N in normal human colonic mucosa and colonic tumors. 137 88

Although gluten withdrawal is likely to remain the mainstay of treatment for adult coeliac disease, many patients find the diet inconvenient and unpalatable and compliance among asymptomatic patients is often poor. Oral corticosteroids have been used for patients who seem to be resistant to gluten withdrawal but preparations with low systemic bioavailability might be preferable. We have given a new glucocorticoid (fluticasone propionate) to 12 adults with untreated coeliac disease for six weeks while they were on a normal diet. One patient defaulted and one suffered a relapse in a pre-existing neoplasm. Excluding these, there was an improvement of symptoms, a mean weight gain of 2 kg, and a rise in albumin of 5.4 g/l. There was a significant improvement in the lactulose/mannitol excretion ratio (p less than 0.05) and in all histological variables examined in paired biopsy specimens (surface and crypt intraepithelial lymphocyte/enterocyte and goblet cell/enterocyte ratios and enterocyte height, p less than 0.01 or better). In six paired specimens sucrase and alkaline phosphatase activity increased in all (p less than 0.05) and lactase in five of six. No appreciable side effects were observed, but two patients had suppressed cortisol values and synacthen responses at six weeks. A further three, with normal pretrial results, had a blunted tetracosactrin response at six weeks. Fluticasone propionate seems worthy of further assessment in the treatment of coeliac disease as an adjunct to gluten withdrawal.
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PMID:A pilot study of fluticasone propionate in untreated coeliac disease. 190 62

Several clonal sublines of HCT-116 human colon adenocarcinoma cells were isolated and characterized on the basis of their growth characteristics, intrinsic enterocyte-like differentiation (as assessed by alkaline phosphatase and lactase activities), and responses to butyrate, an inducer of colon tumor cell maturation. The HCT-116 sublines were found to be heterogeneous and several phenotypically distinct clones were identified. Further characterization of these clones indicated that the effects of butyrate on cell growth, alkaline phosphatase activity, and lactase activity were distinct and separable. The growth of all of the clones were inhibited by butyrate (IC50 values varied from 0.44 to 1.5 mM), but the effects of this agent on alkaline phosphatase and lactase activities varied widely. In several sublines butyrate had no effect on either enzyme while in others one or both activities were induced. Additionally, the binding of 125I-epidermal growth factor (EGF) to cell surface receptors was found to be proportional to the expression of lactase activity in the cell. The D3 clone and other sublines with intrinsic lactase activities greater than 100 nmol/mg/min expressed a class of high-affinity EGF receptors (e.g., D3 cells had 3.48 X 10(4) EGF receptors/cell with a kd of 0.61 nM). Other clones with less lactase activity had undetectable levels of 125I-EGF binding. In clones which exhibited greater than twofold increases in lactase activity in response to butyrate, the expression of a large number of low-affinity EGF receptors was also induced. In one such clone, the P1 subline, lactase activity was increased from 70 nmol/mg/min to 230 nmol/mg/min after 96 h in 2 mM butyrate, and the expression of EGF receptors was increased from undetectable levels to 1.18 X 10(5) EGF receptors/cell (kd of 3.2 nM). Northern blot analysis indicated that the increased 125I-EGF binding after butyrate treatment may have been due, in part, to a greater than twofold accumulation of EGF receptor mRNA. In addition, the expression of the messages for transforming growth factor alpha (TGF-alpha) and transforming growth factor beta (TGF-beta) was examined in butyrate-treated cells. While TGF-alpha mRNA levels were found to correlate with EGF receptor message levels in the HCT-116 clones, TGF-beta mRNA expression was not found to correlate with the butyrate-induced growth inhibition or with increases in EGF receptor expression, alkaline phosphatase activity, or lactase activity in these cells.
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PMID:Increased cell surface EGF receptor expression during the butyrate-induced differentiation of human HCT-116 colon tumor cell clones. 197 61

Nine monoclonal antibodies were prepared against luminal membranes purified from rat intestinal cells at day 19 of gestation, and seven of them were found to define antigens common to adult crypt cells and fetal or embryonic intestinal epithelial cells. The FBB 2/29 antigen was first detected over the entire intestinal epithelial population at days 14-15 of gestation, a period of development characterized by formation of a stratified intestinal epithelium and differentiation of the surrounding mesenchyme. This antigen, identified as a set of high molecular mass proteins, became restricted to the crypt and lower villus cells after birth and was exclusively expressed by the crypt cells in adult intestine. It also was found to be expressed by the epithelial cells of the distal tubuli in the kidney of adult rats and by cultured human tumor colonic cells. The FBB 1/54/1, FBB 3/46, and FBB 3/78/9 antibodies stained only the epithelial cells present at the base of the villi in fetal intestine, starting at days 20-21 of gestation (about 1-2 days before birth), and stained the crypt and lower villus cells in newborn and adult intestine; these antigens may be regarded as specific markers for the developing crypt cells in fetal intestine shortly before birth. The FBB 1/20 and FBB 4/2 antigens were first detected on the fetal intestinal cells at day 18 of gestation; they were located over the entire epithelium in newborn rats and became restricted to the crypts after weaning. The FBB 2/28 antigen was expressed by the entire intestinal epithelium at all stages of development, starting from days 18-19 of gestation in the fetus. Two antibodies, FBB 3/4 and FBB 3/24, were found to be specific for lactase. These results have demonstrated the expression of cell- and tissue-specific components in rat intestine during early embryonic development and revealed a marked similarity in surface membrane antigens between fetal intestinal epithelial cells and adult crypt cells.
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PMID:Fetal characteristics of small intestinal crypt cells. 351 86

The serum lactase dehydrogenase (LDH) of 56 patients with Ewing's sarcoma was examined to determine the use of LDH as a tumor marker. The initial LDH level was used to determine its ability to predict survival. The follow-up LDH level also was examined, as an indicator of recurrent disease. The initial LDH level was found to have no prognostic value. Both patients with elevated and normal LDH levels had the same survival rate. The LDH level at recurrence was significantly higher, however, than the follow-up LDH level of those without recurrence (P less than 0.001). The LDH level was most sensitive as a tumor marker for recurrent disease in those patients with multiple sites of tumor involvement at the time of recurrence.
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PMID:Lactase dehydrogenase as a tumor marker for recurrent disease in Ewing's sarcoma. 381

Glutamine supplementation has been advocated for patients requiring parenteral nutritional support. However, the direct effect of glutamine on neoplastic cells is poorly understood. We therefore investigated the effects of glutamine on the proliferation, differentiation, and cell-matrix interactions of two human colon carcinoma cell lines (Caco-2 and SW620) adapted to glutamine-free media. Doubling times were calculated by logarithmic transformation of serial cell counts. Alkaline phosphatase, cathepsin C (dipeptidyl peptidase), lactase, and isomaltase expression (markers of differentiation) were assayed by digestion of synthetic substrates. Adhesion to matrix proteins was assessed by colorimetric quantitation of toluidine blue staining of adherent cells. Surface expression of Caco-2 receptors for matrix proteins (integrins) was studied by biotinylation and immunoprecipitation with specific antibodies. Glutamine (1-10 mM) dose-dependently stimulated Caco-2 proliferation on all matrices studied with maximal effect at 7 mM. For instance, Caco-2 doubling time on collagen IV decreased by 57 +/- 0.2% (SE) (P < 0.001). Glutamine inhibited the expression of all four digestive enzymes with maximal inhibition ranging from 10 to 40% (P < 0.05 for all). Adhesion to matrix proteins was markedly diminished (51 +/- 1%, P < 0.01) by glutamine (5 mM) treatment, correlating with decreased alpha 2 and beta 1 integrin subunit surface expression. Glutamine had similar effects on SW620 cells, stimulating proliferation, inhibiting digestive enzyme expression, and diminishing both adhesion and integrin surface expression. Glutamine supplementation modulates the phenotype of at least two human colon carcinoma cell lines, increasing proliferation, decreasing differentiation, and decreasing adhesion to matrix proteins in association with decreased integrin expression. Although the mechanisms of these effects await elucidation, such characteristics would appear to predict more aggressive tumor behavior and raise the possibility that nutritional supplementation with glutamine may be deleterious in patients with cancer.
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PMID:Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines. 795 30

Human colon adenocarcinoma cells, treated with deoxycholate for 24 h prior to exposure to 1 mM butyrate, exhibited dose-dependent increases in the activities of three markers of colonic differentiation (alkaline phosphatase, lactase and CEA). Treatment with deoxycholate alone, for 24 h or longer, did not increase the secretion of CEA or the activities of either of the brush border-associated enzyme activities. Increases in differentiation markers were found to be bile acid-specific. Pretreatment with either dehydrocholic acid or cholic acid, even at cytotoxic concentrations, led to no significant butyrate-induced increases in brush-border associated hydrolase activities. The addition of a bacterial superoxide dismutase decreased the short-term cytotoxicity of deoxycholate and increased the maturation-potentiating effects of the bile acid in HCT-116 DO cells. The results of these studies demonstrate that bile acids, which are commonly thought to have tumor promoting activities in vivo, may also have physiological effects which serve to limit carcinogenic processes in the human colon by potentiating tumor cell differentiation.
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PMID:Potentiation of butyrate-induced differentiation in human colon tumor cells by deoxycholate. 851 44

Sucrase-isomaltase (SI), trehalase (T) and lactase-beta-glucosidase (LG) activities were assessed histochemically in samples of colorectal adenomas (11 tubular, 12 tubulovillous, 10 villous) and 30 adenocarcinomas obtained by biopsy during colonoscopy or from specimens removed by surgical intervention. Small samples of tumor tissue, tissue of the transitional zone and of macroscopically normal mucosa were quenched in heptan cooled in an acetone-dry ice mixture. Cryostat sections, transferred to non-precooled slides and in some cases to semipermeable membranes, were dried and subjected to the histochemical reactions for SI, T and LG. Sucrose, 2-naphthyl, 6-Br-2-naphthyl, and 5-Br-4-Cl-3-indoxyl alpha-D-glucosides, trehalose, and 5-Br-4-Cl-3-indoxyl-beta-D-fucoside were used as substrates. Sections of jejunal biopsies with normal activities of brush border glycosidases were used as controls. From samples of 5 adenomas, 5 adenocarcinomas and collected rests of jejunal biopsies with a normal finding 10% (w/vol) homogenates in 2% Triton X-100 were prepared. Homogenates were frozen and thawed 3 times and their supernatants subjected to isoelectric focusing on polyacrylamide gel plates. Zymograms were developed with the same methods as for the detection of alpha-glucosidases in sections. In no colorectal tumor LG was present. SI was found in 70% adenocarcinomas, 50% villous, 25% tubulovillous and 19% tubular adenomas when the method with sucrose, glucose oxidase-peroxidase and 3,3'-diaminobenzidine was used. Hardly discernible traces of activity were found in tumors with azo-coupling reactions applied at pH 5, 6 and 6.5. No reaction was detected with the indigogenic method applied at pH above 6.0. However, jejunal biopsies displayed very strong reactions confined to the brush border of enterocytes under the same conditions. A strongly positive reaction was seen in 7 of 12 tumors investigated recently when the indigogenic reaction was applied at pH below 6.0 (particularly at pH 5.0). In this case the deposition of indigo was due to membrane and lysosomal alpha-glucosidases of the tumor cells and lysosomal alpha-glucosidase of macrophages and leukocytes. These findings were corroborated by zymograms. T was detected in the same tumors as SI; its activity was lower, however. SI activity in colorectal tumors is a useful, but not general marker of these tumors.
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PMID:Sucrase-isomaltase and other brush border glycosidases in colorectal tumors. 886 57

Cutaneous melanoma is a significant and increasing clinical problem. Knowing accurately the prognosis in a given patient is critical for treatment decisions and for optimal patient education. In this article we discuss the most current information regarding prognostic factors in early-stage and advanced malignant melanoma. Tumor thickness and ulceration are the most important predictors for primary melanoma. Number of positive lymph nodes is the most powerful predictor for stage III patients, and sites of disease and lactase dehydrogenase levels are the most useful predictors in metastatic disease.
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PMID:The changing prognosis of melanoma. 1112 60


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