Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using proton magnetic resonance spectroscopy (1H MRS) spectra were obtained in vitro from extracts of four types of lung cancer (squamous cell, adenocarcinoma, large cell, small cell) and normal lung. The hydrophilic phase of the chloroform/methanol-water extracts yielded several distinct peaks. Among them the peak areas for cholines, creatines, glycine, and alanine, and their ratios were calculated and used as parameters to characterize different lung tissues. The ratios, cholines/alanine and glycine/alanine, were significantly (P < 0.001 to P < 0.05) higher for the normal lung than lung cancers. Creatines/glycine and creatines/cholines generally provided good discrimination (P < 0.001 to P < 0.05) between any two types of lung cancer. When data were further analyzed by discriminant factor analysis, there was 81.5 to 90.7% accuracy in predicting between normal lung and each cancer type, or among the four types of lung cancer. These results suggested that 1H MRS might be useful as an adjunct modality in the differential diagnosis of lung cancers.
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PMID:In vitro characterization of lung cancers by the use of 1H nuclear magnetic resonance spectroscopy of tissue extracts and discriminant factor analysis. 838 59

Thirty-four patients showing cystic intracranial mass lesions on MR imaging were evaluated by in vivo proton MR spectroscopy (MRS) with the aim of detecting lesion-specific spectral patterns that may assist imaging in better tissue characterization. In vivo spectroscopy was performed using stimulated echo acquisition mode with echo times 20 and 270 m in all, and spin echo with echo time 135 m in 11 patients. All primary neoplasms (intra-as well as extra-axial) showed choline (3.22 ppm) resonance along with lipid and/or lactate (1.3 ppm). It was not possible to grade cystic gliomas based on N-acetyl asparate-to-choline ratio. High-grade gliomas (n = 8) showed lipid/lactate and low-grade gliomas (n = 6) showed only lactate. Seven patients with brain abscess showed resonances only from acetate (1.92 ppm), lactate (1.3 ppm) and alanine (1.5 ppm). Two cases of metastatic adenocarcinoma showed only lipid/lactate. In 7 patients with epidermoid cyst, lactate along with an unassigned resonance at 1.8 ppm was observed and could be easily differentiated from arachnoid cysts (n = 2), which showed only minimal lactate. A case of cystic meningioma could be differentiated from cystic schwannoma by the presence of alanine in the former. It is concluded that MR imaging, when combined with in vivo MRS, may help to better characterize intracranial cystic mass lesions.
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PMID:Cystic intracranial mass lesions: possible role of in vivo MR spectroscopy in its differential diagnosis. 858 66

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.
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PMID:Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability. 906 23

Mammalian selenocysteine-containing thioredoxin reductase (TR) isolated from HeLa cells and from human lung adenocarcinoma cells was separated into two major enzyme species by heparin-agarose affinity chromatography. The low-affinity enzyme forms that were not retained on heparin agarose showed strong crossreactivity in immunoblot assays with anti-rat liver TR polyclonal antibodies, whereas the high-affinity enzyme forms that were retained by the heparin column were not detected. Both low and high heparin-affinity enzyme forms contained FAD, were indistinguishable on SDS/PAGE analysis, and exhibited similar catalytic activities in the NADPH-dependent DTNB [5,5'-dithiobis(2-nitrobenzoate)] assay. The C-terminal amino acid sequences of 75Se-labeled tryptic peptides from lung adenocarcinoma low- and high heparin-affinity enzyme forms were identical to the predicted C-terminal sequence of human placental TR. These two determined peptide sequences were -Ser-Gly-Ala-Ser-Ile-Leu-Gln-Ala-Gly-Cys-Secys-(Gly). Occurrence of the Se-carboxymethyl derivative of radioactive selenocysteine in the position corresponding to TGA in the gene confirmed that UGA is translated as selenocysteine. The presence of cysteine followed by a reactive selenocysteine residue in this C-terminal region of the protein may explain some of the unusual properties of the mammalian TRs.
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PMID:Heparin-binding properties of selenium-containing thioredoxin reductase from HeLa cells and human lung adenocarcinoma cells. 917 83

The aim of the present study was to investigate the earlier finding that cAMP stimulation activates Na+/glucose cotransport in intestinal epithelia. Western blotting demonstrated the existence of Na+/glucose cotransporters in the colonic adenocarcinoma cell line HT29 cl.19A. Monolayers of this cell type showed a glucose transport, which was inhibited by 0.5 mM phlorizin (specific inhibitor of Na+/glucose cotransport). Brush border membrane vesicles of HT29 cl.19A cells exhibited a Na(+)-gradient dependent glucose transport, which was stimulated by DbcAMP-pretreatment (dibutyryladenosine 3',5'-cyclic monophosphate) of the cells. In the Ussing chamber, glucose (10 mM) unexpectedly lacked stimulatory effect on short circuit current (Isc) in HT29 cl.19A monolayers in the control situation. In DbcAMP-stimulated monolayers, glucose induced a complex Isc-response consisting of both stimulatory and inhibitory components, usually leading to a 'net' stimulation of lsc. Phlorizin (0.5 mM) did not prevent the stimulatory effect of glucose. Mannitol, alanine, fructose, ethanol (solvent for phlorizin) and the non-metabolizable glucose analogue 3-o-methyl-alpha-glucopyranoside inhibited Isc in a similar fashion as did phlorizin. Glucose transport in human colon biopsies were studied both in [14C]glucose accumulation experiments and in a specially designed Ussing chamber. There were no indications of glucose absorption in neither of these experiments. We conclude: (1) The human colon lacks Na+/glucose transport, (2) HT29 cl.19A cells exhibit Na+/glucose cotransport, which is stimulated by cAMP, (3) but this mechanism seem to be of a different type from the Na+/glucose cotransport of the 'normal' small intestine.
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PMID:Na+/glucose cotransport in the colonic adenocarcinoma cell line HT29 cl.19A: effect of cAMP. 920 45

Thyroid transcription factor 1 (TTF-1) is a homeodomain-containing nuclear transcription factor expressed in epithelial cells of the lung and thyroid. TTF-1 binds to and activates the transcription of genes expressed selectively in the respiratory epithelium including pulmonary surfactant A, B, C and Clara cell secretory protein. Transfection with a plasmid encoding the cyclic AMP-dependent protein kinase (protein kinase A; PKA) catalytic subunit, Cat-beta, stimulated the phosphorylation of a TTF-1-flag fusion protein 6-7-fold in H441 pulmonary adenocarcinoma cells. Recombinant TTF-1 was phosphorylated by purified PKA catalytic subunit in the presence of [gamma-32P]ATP. PKA catalytic subunit family members, Cat-alpha and Cat-beta, markedly enhanced the transcriptional activation of surfactant B gene promoters by TTF-1 in vitro. Peptide mapping was used to identify a PKA phosphorylation site at the NH2 terminus of TTF-1. A 17-amino acid synthetic peptide comprising this site completely inhibited the PKA-dependent phosphorylation of TTF-1 in vitro. A substitution mutation of TTF-1 (Thr9 two head right arrow Ala) abolished phosphorylation by PKA and reduced transactivation of the surfactant B gene promoter. Transfection with a plasmid encoding the cAMP regulatory element binding factor inhibited transcriptional activity of the surfactant protein B gene promoter. Phosphorylation of TTF-1 mediates PKA-dependent activation of surfactant protein B gene transcription.
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PMID:Protein kinase A activation of the surfactant protein B gene is mediated by phosphorylation of thyroid transcription factor 1. 921 70

A cDNA for the GATA-6 (GATA-GT1) DNA binding protein was cloned from a library of the human gastric adenocarcinoma cell line MKN45. The deduced amino acid sequence (449 residues) indicates that the primary structure of human GATA-6 is highly homologous to that of the rat protein. The potential phosphorylation site for protein kinases (A and C), and histidine and alanine clusters are conserved. Whereas the rat H+/K+-ATPase alpha and beta subunit genes have two and three GATA protein binding sites in their promoter regions, respectively, the human alpha subunit gene has only one binding site [Maeda, M., Kubo, K., Nishi, T. and Futai, M. (1996) J. Exp. Biol. 199, 513-520]. We cloned the 5'-upstream region of the human H+/K+-ATPase beta subunit gene by genome walking and found that it also has a single GATA protein binding site near the TATA box. The GATA sites of the human alpha and beta subunit genes are recognized by the zinc finger domain of human GATA-6. The conservation of the GATA protein binding sites suggests that they are important for the gene regulation of the human and rat H+/K+-ATPase.
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PMID:GATA-6 DNA binding protein expressed in human gastric adenocarcinoma MKN45 cells. 931 13

In order to determine the topographical distribution of the K-ras codon 12 mutations in carcinoma and preneoplastic lesions of the lung, selective ultraviolet radiation fractionation, as well as microdissection followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP), was performed. Fourteen of 61 samples amplified (23.0%) had a mutation in the K-ras codon 12. Of 41 adenocarcinoma, 12 samples (29.3%) had a mutation, whereas none of the squamous cell carcinomas had a mutation. One of six large-cell carcinomas, one of three carcinoid tumours and none of three other carcinomas had a mutation. Direct sequencing revealed that K-ras codon 12 of six samples were TGT (Cys), five samples were GTT (Val), two samples were GCT (Ala) and one sample was TTT (Phe). A total of 113 lesions of 13 cases covered by dot were amplified after UV radiation. All of 74 carcinoma lesions had the mutation, and intratumour heterogeneity was not observed. Of 39 non-malignant lesions, one type II cell hyperplasia had the mutation, which suggests that the K-ras mutation occurs in the early stage of carcinogenesis. The lack of intratumour heterogeneity supports the hypothesis.
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PMID:K-ras point mutation occurs in the early stage of carcinogenesis in lung cancer. 951 49

The levels of cathepsins in malignant and surrounding nonmalignant lung tissue were determined in 17 non-small cell lung cancer specimens. Cathepsin (Cat) D activity was assayed using hemoglobin, whereas Cat B and Cat L activities were assayed using fluorimetric substrates, benzoylcarbonyl-Ala-Arg-Arg-7-amino-4-methylcoumarine and benzoylcarbonyl-Phe-Arg-7-amino-4-methylcoumarine, respectively. Cat protein concentrations were determined using ELISAs. In malignant tissues, the activities of Cat B and Cat L were significantly higher than the activities in nonmalignant tissues (P < 0.0012 and P < 0.0003, respectively), whereas Cat D concentration was not. There was also a 5.6-fold increase in median Cat B protein (P < 0.054) and a 2.2-fold increase in Cat L protein (P < 0.069). By contrast, the aspartic proteinase, Cat D protein, was not significantly increased in tumors versus control lung tissues. Moderate but significant correlation (r = 0.5, P < 0.045) between Cat B and Cat L expression was observed, but neither correlated with Cat D. The relative increase in median Cat L activity (P < 0.037) and protein (P < 0.0005) was greater in poorly differentiated tumors than in moderate ones. Cat L activity (P < 0.003) and protein (P < 0. 005) increases were higher in adenocarcinoma than in squamous cell carcinoma. We conclude that in lung cancers the three lysosomal enzymes are regulated in a noncoordinate manner and that there is specific induction of cysteine cathepsins. Whether Cat B and/or Cat L would be of diagnostic and/or prognostic value requires further study in a larger patient population.
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PMID:Cathepsins D, B, and L in malignant human lung tissue. 981 4

The novel oral hypoglycemic agent nateglinide (AY4166) is a nonsulfonylurea insulin secretagogue, and its pharmacokinetic features include rapid absorption and elimination. As nateglinide is a dipeptide-like drug, we investigated the interaction of nateglinide with peptide transporters PEPT1 and PEPT2, which mediate the absorption of various peptide-like drugs. Nateglinide exhibited a potent inhibitory effect on [14C]glycylsarcosine uptake by the human colon adenocarcinoma cell line Caco-2 and rat PEPT-transfectants. Kinetic analysis revealed that these inhibitory effects were noncompetitive. Na(+)-coupled alanine or threonine uptake by Caco-2 cells was not inhibited by nateglinide, suggesting that the inhibitory effect of nateglinide on peptide transporters was not due to nonspecific interaction. There was little uptake of [14C]nateglinide by peptide transporters. Various sulfonylureas, such as glibenclamide, also inhibited [14C]glycylsarcosine uptake by rat PEPT-transfectants. In conclusion, nateglinide as well as sulfonylureas inhibit the transport activity of PEPT1 and PEPT2, although nateglinide itself is not transported by these transporters.
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PMID:Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. 1074 66


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