Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoblasts express high levels of liver/bone/kidney alkaline phosphatase (LBK AP), an enzyme critical for bone formation. Other tissues and cell types generally express much lower levels of LBK AP and correspondingly lower levels of mRNA. In light of our early observations that the human LBK AP promoter is expressed equally when transfected into a variety of different cells, we have carried out a detailed study of LBK AP gene expression in Saos-2 cells which are osteoblast-derived and express high levels of LBK AP mRNA, and in HepG2 hepatoblastoma cells which express LBK AP mRNA at levels which are approximately 1000-fold lower. Our results indicate that both of these cells utilize the same promoter sequences to initiate transcription of their LBK AP genes at roughly the same rates. Moreover, the stability of cytoplasmic LBK AP mRNA is equal in both cell types. The lack of any apparent buildup of unspliced precursor mRNA in the nucleus of HepG2 cells leads us to the conclusion that splicing (and nuclear export) is equivalent. It is therefore likely that differential expression is controlled at a very early step post-transcription, possibly by sequences that destabilize the nascent RNA in HepG2 cells. We reason that these destabilizing sequences are located in the gene's introns because a transfected LBK AP minigene, comprised of the full length cDNA and flanking sequences, is expressed efficiently in both cell types.
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PMID:Post-transcriptional regulation of the human liver/bone/kidney alkaline phosphatase gene. 199 14

Pleural effusion, secondary to a metastasis from a malignant hepatoblastoma, was diagnosed in a 3-year-old Appaloosa gelding. Severe hemorrhagic transudate in both pleural cavities resulted in acute onset of labored breathing, tachypnea, tachycardia, and jugular vein pulsation. Results of ultrasonography and radiography of the ventral lung field and cranial portion of the abdomen initially were nondiagnostic, as were results of cytologic examination of peritoneal fluid and tracheal wash specimens. Moderately high serum gamma-glutamyl transferase and alkaline phosphatase activities, despite normal hepatocyte-specific enzyme (sorbital dehydrogenase) activity, were indicative of biliary stasis without hepatocyte destruction. The horse was euthanatized. Necropsy revealed a 47-kg hepatoblastoma, with metastases in the lungs and intestines.
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PMID:Pleural effusion resulting from malignant hepatoblastoma in a horse. 253 79

Isozyme patterns of alkaline phosphatase (ALP) were electrophoretically examined in human cell lines derived from one hepatoblastoma, five hepatocellular carcinomas (HCCs) and two cholangiocellular carcinomas. Most of the cell lines tested had a liver-type ALP isozyme. In addition, an abnormal ALP isozyme, which was similar to variant ALP, was detected in one hepatoblastoma and two HCC cell lines. One HCC cell line of these variant-like ALP-positive cell lines was alpha-fetoprotein (AFP)-negative. These findings suggest that variant-like ALP may be useful for the identification of human hepatoma cell lines, especially in AFP or albumin-negative cell lines.
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PMID:Alkaline phosphatase expression in human cell lines derived from primary hepatomas. 256 37

The effect of the nucleoside anti-metabolite tiazofurin (TR) was examined on the growth and phenotypic alterations of MCF-7 breast cancer and HBL-100 normal breast cell lines. TR was shown to inhibit MCF-7 cell growth. This inhibition could be reversed by exogenous addition of guanosine. The anti-proliferative effect of TR is accompanied by phenotypic alterations that include lipid accumulation and an increase in alkaline phosphatase activity. In contrast to MCF-7 cells, the HBL-100 breast milk derived cell line is relatively resistant to inhibition by TR. Alkaline phosphatase is not affected by TR and untreated cells accumulate lipid droplets, similar to TR-treated MCF-7 cells. Determination of GTP and ATP pools in both cell lines revealed that TR markedly reduces GTP content in MCF-7 cells. In HBL-100 cells, TR induces only a small decrease in GTP and does not affect ATP levels. The prototypic IMP dehydrogenase inhibitor, mycophenolic acid (MA), markedly inhibits HBL-100 cell growth, similarly to its effect on MCF-7 breast cancer cells. These findings may suggest differential metabolism of TR in MCF-7 and HBL-100 cells.
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PMID:Growth inhibition and induction of phenotypic alterations by tiazofurin: differential effects on MCF-7 breast cancer and HBL-100 breast cell lines. 273 21

Two enzyme forms of alkaline phosphatase have been partially purified from the medium spent for the culture of HUH-6 clone 5 cells, which were originally derived from hepatoblastoma tissue. The purification methods used are ammonium sulfate precipitation, ethanol precipitation, diethylaminoethyl cellulose chromatography, Affi-Gel Blue chromatography, and Sephadex G-200 gel filtration. These alkaline phosphatases have been characterized by thermostability, inhibition, and immunological and electrophoretic studies. Both are L-phenylalanine and L-tryptophan sensitive and L-homoarginine and L-leucylglycylglycine insensitive, and both react with an antiserum against intestinal alkaline phosphatase. The major enzyme form is a neuraminidase-cleavable, moderately thermostable isoenzyme which on polyacrylamide gel shows an electrophoretic mobility similar to that of liver alkaline phosphatase. The minor enzyme form is a neuraminidase-uncleavable, thermolabile isoenzyme which shows an intermediate electrophoretic mobility between liver and hepatoma alkaline phosphatases. The molecular weights of the major and minor enzymes have been estimated by gel filtration to be 170,000 and 110,000, respectively. These results support the conclusion that the two enzyme forms of HUH-6 alkaline phosphatase are intestinal in type, with the major enzyme form closely resembling hepatoma and oncoamnionic alkaline phosphatases, and the minor enzyme form resembling "intestine-like liver alkaline phosphatase." HUH-6 clone 5 cell line may be a useful in vitro model to study the regulatory mechanism for phenotypic expression of intestinal-type alkaline phosphatase isoenzymes in liver cancer cells.
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PMID:Intestinal-type alkaline phosphatase produced by human hepatoblastoma cell line HUH-6 clone 5. 631 71

The importance of the oncofetal glycoprotein antigen alphafetoprotein (AFP) as a tumor marker is well documented. Structural heterogeneity of AFP molecules due to its associated carbohydrate moieties has also been demonstrated. In the present study, molecular variants of AFP, Concanavalin A reactive (R Con A) and Concanavalin A nonreactive (NR Con A) were quantified in five cases of hepatocellular carcinoma (HCC), three cases of hepatoblastoma, five gonadal and two extragonadal germ cell tumors, and two suspected liver secondaries by employing crossed immunoaffino electrophoresis (CIAE). AFP peaks were localized using anti-AFP antibodies conjugated to alkaline phosphatase. Characteristic patterns of AFP R Con A and NR Con A fractions were obtained in different AFP-secreting malignancies. Serum samples of HCC and hepatoblastoma were predominantly composed of R Con A AFP, while gonadal and extragonadal germ cell tumors showed significant reduction of R Con A AFP and elevation of NR Con A AFP. Analysis of AFP variants in sera from two patients of suspected liver metastasis with elevated AFP confirmed liver secondaries arising from germ cell tumor in one patient and HCC in the other patient. The present study highlights the importance of AFP microheterogeneity analysis not only as diagnostic aid for the differential diagnosis of AFP-secreting tumors, but also in providing better management and prognosis.
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PMID:Clinical relevance of alphafetoprotein microheterogeneity in alphafetoprotein-secreting tumors. 753 46

Epidemiological, clinical, biochemical and topographic features of primary hepatic cancer (PHC) were reviewed retrospective and prospectively in this study. This review consisted of 76 patients from 1971 to 1990. Forty nine males and 27 females. The mean age was 66.1 +/- 11.7 years. Hepatocellular carcinoma (HC) was the most frequent histological type (84.1%), followed by cholangiocarcinoma (87.7%). Mixed carcinoma and hepatoblastoma were 4.3 and 2.9% respectively. The prevalence af PHC among 1485 autopsies was 0.74%. The most frequent sites af metastasis were the lungs (66%) and portal vein (50%). Hepatocellular carcinoma was associated to cirrhosis in 80% of the cases. A syndrome including asthenia, weight loss, hepatomegaly and cholestasis was identified in most of the patients, and alkaline phosphatase was the most frequently disturbed laboratory test. 60% of tumors were bilateral and none of the solitary tumors had less than 5 cms in diameter. 20% of HC showed normal serum levels of AFP (< 20 ng/ml). 40% had at least one of the markers of B virus hepatitis in serum.
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PMID:[Primary liver cancer. Its epidemiological, clinical and biochemical characteristics]. 820 48

Human breast (MCF-7, HBL 100, T47D, BT20, HS578T), colon (HT29, CACO2, SW620, SW480, COLO320DM) and small cell lung cancer (NCI-N417, OH3, SW2) cell lines were transplanted subcutaneously into severe combined immunodeficient (SCID) mice. When sizeable tumours developed, the mice were sacrificed and the following enzyme activities were detected histochemically: presumed nitric oxide synthase-associated diaphorase (NOSaD), beta-D-glucuronidase (beta-Gluc) and non-specific alkaline phosphatase (alP). Except for HT29 and MCF-7 presumed NOSaD activity was not detected in the tumour itself or in the neo-vasculature of the tumours. beta-Gluc activity was found in all tumour cells (except N417 and COLO 320), in the necrotic parts of the tumours and in stromal cells of the tumour bed. AlP activity was present in all tumours including their necrotic areas. However, the activities of beta-Gluc and alP varied considerably even within one tumour, ranging from very weak to very strong. Principally the results show that the human/SCID mouse tumour model is well suited to test modern applications of tumour therapy involving the enzymes NOSaD, beta-Gluc and alP. In particular, antibody directed enzyme prodrug therapy concepts and activation of prodrugs by enzymes released from tumour cells into the necrotic areas of the tumour can be evaluated in this in vivo model.
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PMID:Histochemistry of therapeutically relevant enzymes in human tumours transplanted into severe combined immunodeficient (SCID) mice: nitric oxide synthase-associated diaphorase, beta-D-glucuronidase and non-specific alkaline phosphatase. 896 Mar 2

To obtain selective antiprogestins, we have examined the in vitro antiprogestational/antiglucocorticoid properties of two novel compounds, CDB-4124 and the putative monodemethylated metabolite, CDB-4453, in transcription and receptor binding assays and compared them to CDB-2914 and mifepristone. All four antiprogestins bound with high affinity to rabbit uterine progestin receptors (PR) and recombinant human PR-A and PR-B (rhPR-A, rhPR-B) and were potent inhibitors of R5020-induced transactivation of the PRE2-tk-luciferase (PRE2-tk-LUC) reporter plasmid and endogenous alkaline phosphatase production in T47D-CO human breast cancer cells. None of these compounds exhibited agonist activity in these cells. Induction of luciferase activity was potentiated about five-fold by 8-Br-cAMP under basal conditions and to the same extent in the presence of the PR antagonists. Mifepristone bound to rabbit thymic glucocorticoid receptors (GR) with approximately twice the avidity of the CDB antiprogestins. Inhibition of GR-mediated transcription of PRE2-tk-LUC was assessed in HepG2 human hepatoblastoma cells. Mifepristone exhibited greater antiglucocorticoid activity than CDB-2914, 4124, and 4453, about 12-, 22-, and 185-fold, respectively. Thus, while there was a good correlation between binding to PR and functional activity of these antiprogestins, GR binding was not predictive of their glucocorticoid antagonist activity. In agreement with our in vivo results, CDB-4124 and CDB-4453, as well as CDB-2914, are potent antiprogestins in vitro, but show considerably less antiglucocorticoid activity than mifepristone.
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PMID:CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914. 1191 51

The chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata (EBV) was evaluated in N-nitrosodiethylamine (DEN, 200 mg/kg) induced experimental liver tumor in rats and human cancer cell lines. Oral administration of ethanol extract of Bauhinia variegata (250 mg/kg) effectively suppressed liver tumor induced by DEN as revealed by decrease in DEN induced elevated levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (GPx) and glutathione S-transferase (GST). The extract produced an increase in enzymatic antioxidant (superoxide dismutase and catalase) levels and total proteins when compared to those in liver tumor bearing rats. The histopathological changes of liver samples were compared with respective controls. EBV was found to be cytotoxic against human epithelial larynx cancer (HEp2) and human breast cancer (HBL-100) cells. These results show a significant chemopreventive and cytotoxic effect of ethanol extract of Bauhinia variegata against DEN induced liver tumor and human cancer cell lines.
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PMID:Chemoprevention and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine induced liver tumors and human cancer cell lines. 1625 58


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