Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the first correlation of Nm23 sequence and its tumor metastasis-suppressive capacity using site-directed mutagenesis and an in vitro tumor cell motility assay. MDA-MB-435 human breast carcinoma cells were transfected with a control expression vector (pCMVBamneo), the vector containing the wild type nm23-H1, or the nm23-H1 vector encoding mutations at the following amino acids: serine 44, a phosphorylation site; proline 96, the k-pn mutation in the Drosophila nm23 homolog that causes developmental defects; histidine 118, involved in Nm23's nucleoside diphosphate kinase activity; and serine 120, a site of mutation in human neuroblastomas and phosphorylation. The wild type nm23-H1 transfectants were 44-98% less motile to serum and 86-99% less motile to autotaxin than control vector transfectants. The proline 96 k-pn, serine 120 to glycine, and to a lesser extent serine 120 to alanine mutant nm23-H1-transfected cell lines exhibited motility levels at or above the control transfectants, indicating that these mutations can abrogate the motility-suppressive phenotype of nm23-H1. No effect was observed on cellular proliferation, nor were the serine 44 to alanine nm23-H1 mutant transfectants motile, demonstrating the specificity of the data. The data identify the first structural motifs of nm23-H1 that influence its metastasis suppressive effect and suggest complex biochemical associations or activities in the Nm23 suppressive pathway.
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PMID:Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells. 881 Feb 65

The deposition of copper on Descemet's membrane and the anterior and posterior lens capsule with extreme hypercupremia and IgG hypergammaglobulinemia has been previously described with multiple myeloma and pulmonary carcinoma. A 66-year-old man presenting with blurred vision was found to have bilateral golden-brown metallic dust-like deposits on the central region of Descemet's membrane and the anterior and posterior lens capsule. Laboratory investigations revealed an elevated serum copper level 10 times the normal level associated with a monoclonal gammopathy and a normal ceruloplasmin level. Copper binding to the serum proteins was investigated by three biochemical methods. The results demonstrated that the major copper binding fraction in the serum was IgG. N-terminal amino acid analysis of the IgG did not find the sequence of Asp-Ala-His, which has been shown to be a copper binding site in albumin. This is the first report of benign monoclonal gammopathy being associated with the ocular deposition of copper.
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PMID:Ocular copper deposition associated with benign monoclonal gammopathy and hypercupremia. 890 88

The genes for either the TSH receptor (TSH-R) or the stimulatory guanine nucleotide-binding protein subunit (Gs alpha) can undergo somatic mutations in thyroid cells, leading to constitutive activation of adenylyl cyclase and the formation of clonal hyperfunctioning thyroid adenomas. Autonomously functioning thyroid adenomas are thought not to be common precursors of thyroid cancer. If this is the case, mutations of the TSH-R or Gs alpha would not be expected to be highly prevalent in thyroid carcinomas. In this paper we report the results of a screen for structural defects in exon 10 of the TSH-R (which includes the whole serpentine structure, but not the extracellular domain) and of Gs alpha in 30 thyroid carcinomas. Five of these were from patients with functioning metastasis, as we hypothesized that if mutations of these genes were to play a role in the progression to malignancy, they would be more likely to manifest in thyroid cancers that retain unusual differentiated function (i.e. capable of synthesizing enough thyroid hormone to render patients euthyroid or hyperthyroid after total thyroidectomy). None of the 30 tumors had activating point mutations of Gs alpha. Only 2 of 30 had somatic mutations of the TSH-R (codon 632: ACC to GCC, Thr to Ala; and ACC to ATC, Thr to Ile, respectively), the latter in a patient with a thyroid hormone-producting follicular carcinoma. These results suggest that events leading to constitutive activation of the adenylate cyclase signal transduction cascade are not a frequent event in the progression toward differentiated thyroid carcinomas.
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PMID:Structural studies of the thyrotropin receptor and Gs alpha in human thyroid cancers: low prevalence of mutations predicts infrequent involvement in malignant transformation. 892 35

Commercially available alanine dosimeters from different manufacturers were purchased for this study. The response of the detectors was evaluated with 60Co gamma radiation in the dose range 0.2-200 Gy, using a small EPR spectrometer dedicated to dosimetry. The batch sensitivity, inter-specimen scattering and background signal for the different selection of dosimeters were evaluated. The usefulness of the alanine dosimetry system for clinical routine is illustrated by in vivo measurements during 192Ir brachytherapy of cervix carcinoma.
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PMID:One year of experience with alanine dosimetry in radiotherapy. 902 76

A 60-kDa glycoprotein named metanestin was identified by molecular cloning. The glycoprotein had a twice-repeated motif of Pro-Gly-Pro-Gly and carried metastasis-associated carbohydrate epitopes. The antibody to the protein portion of metanestin strongly reacted with lymph-node metastasis of transitional-cell carcinoma of the urinary bladder, but the reactivity to the primary tumor was generally weaker and the normal urothelium was scarcely reactive. Thus both metanestin and the carbohydrate on it showed metastasis-associated expression. In addition, we identified a 100-kDa glycoprotein with a 4-times-repeated motif of Pro-Ala-Pro-Ala. The antibody to the 100-kDa glycoprotein showed reactivity similar to that to metanestin.
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PMID:Metanestin, a glycoprotein with metastasis-associated expression in transitional cell carcinoma of the urinary bladder. 903 62

We previously compared the structure and motility suppressive capacity of nm23-H1 by transfection of wild type and site-directed mutant forms into breast carcinoma cells. Wild type nm23-H1 and an nm23-H1(S44A) (serine 44 to alanine) mutant suppressed motility, whereas the nm23-H1(P96S), nm23-H1(S120G), and to a lesser extent, nm23-H1(S120A) mutant forms failed to do so. In the present study wild type and mutant recombinant Nm23-H1 proteins have been produced, purified, and assayed for phosphorylation and phosphotransfer activities. We report the first association of Nm23-H1 mutations lacking motility suppressive capacity with decreased in vitro activity in histidine-dependent protein phosphotransferase assays. Nm23-H1(P96S), a Drosophila developmental mutation homolog, exhibited normal autophosphorylation and nucleoside-diphosphate kinase (NDPK) characteristics but deficient phosphotransfer activity in three histidine protein kinase assays, using succinic thiokinase, Nm23-H2, and GST-Nm23-H1 as substrates. Nm23-H1(S120G), found in advanced human neuroblastomas, exhibited deficient activity in several histidine-dependent protein phosphotransfer reactions, including histidine autophosphorylation, downstream phosphorylation on serines, and slightly decreased histidine protein kinase activity; significant NDPK activity was observed. The Nm23-H1(S120A) mutant was deficient in only histidine-dependent serine autophosphorylation. Nm23-H1 and Nm23-H1(S44A) exhibited normal activity in all assays conducted. Based on this correlation, we hypothesize that a histidine-dependent protein phosphotransfer activity of Nm23-H1 may be responsible for its biological suppressive effects.
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PMID:Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro. 903 58

The extracellular matrix glycoprotein thrombospondin-1 (TSP1) inhibits angiogenesis, endothelial cell growth, motility and adhesion. Peptides from the type I repeats of TSP1 mimic the adhesive and growth inhibitory activities of the intact protein and specifically interact with heparin and transforming growth factor-beta (TGF beta). To define the structural basis for the antiangiogenic activities of these peptides, we prepared analogs of the TSP1 peptide KRFKQDGGWSHWSPWSSC. L-forward, L-reverse, and D-reverse (retro-inverso) analogs displayed identical activities for binding to heparin, demonstrating a lack of stereospecificity for heparin binding. The L-reverse and D-reverse peptides, however, had somewhat decreased abilities to activate latent TGF beta. Conjugation of the forward peptides through a C-terminal thioether and the reverse peptides through an N-terminal thioether to polysucrose abolished the adhesive activity of the peptides and enhanced their antiproliferative activities for endothelial and breast carcinoma cells stimulated by fibroblast growth factor-2. Their antiproliferative activities were independent of latent TGF beta activation, because substitution of an Ala residue for the essential Phe residue in the TSP1 type-1 repeat peptide increased their potency for inhibiting TSP1 binding to heparin and for inhibiting endothelial cell proliferation. Although the conjugated peptides were inactive in vivo, an unconjugated retro-inverso analog of the native TSP peptide inhibited breast tumor growth in a mouse xenograft model. Thus, these TSP-derived peptide analogs antagonize endothelial growth through their heparin-binding activity rather than through activation of latent TGF beta or increasing cell adhesion. These stable analogs may therefore be useful as therapeutic inhibitors of angiogenesis stimulated by fibroblast growth factor-2.
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PMID:Antiproliferative and antitumor activities of D-reverse peptides derived from the second type-1 repeat of thrombospondin-1. 930 85

Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits cis-diamminedichloroplatinum (cisplatin)-induced poly(ADP-ribose) polymerase degradation and apoptosis, without altering Bcl-2, Bcl-X(L), or Bax expressions. Galectin-3 contains the NWGR amino acid sequence highly conserved in the BH1 domain of the bcl-2 gene family, and a substitution of glycine to alanine in this motif abrogated its antiapoptotic activity. Our findings demonstrate that galectin-3 inhibits apoptosis through a cysteine protease pathway and highlight the functional significance of the NWGR motif in apoptosis resistance of a non-Bcl-2 protein.
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PMID:Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. 939 48

Examples of in vivo detection of skin neoplasmas (Mercl, melanoma) and breast carcinoma using laser induced fluorescence (LIF) and bis-1[1-alanylo-N]-ethylodeuteroporphyrin (Ala-PP) are described in this study. Photosensitizer, wave titanium laser and standard CCD camera coupled to vision amplifier enable precise neoplasm imaging, Ala-PP retention monitoring and further photodynamic therapy (PDT).
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PMID:Protoporphyrin derivatives--the use in localization of neoplasmas by titanium laser-induced fluorescence technique. 941 3

Different Epstein-Barr-virus(EBV) variants were found to be associated with nasopharyngeal carcinoma (NPC). The type-C variant lacks the BamHI site between the BamHI W1* and I* regions and the type-f variant has an extra BamHI site in the BamHI F fragment. The BNLF1 gene (which encodes the LMP1 protein) from a nude-mouse-passaged CAO strain and from NPC biopsies from Taiwanese patients also exhibits variations resulting in structural and functional differences in the protein. The BZLF1 gene encodes the ZEBRA protein which triggers the EBV lytic cycle. A difference has been observed in 8 amino acids in the ZEBRA sequence in B95-8 (Z95) and P3HR1 (ZP3) cell lines. EBV found in NPC biopsies and peripheral-blood cells from Asians was predominantly of the ZP3 type (72%), while 81% of samples from different EBV-associated diseases and peripheral-blood cells from North Africa or Europe were of the Z95 type. We found that an alanine 206 had been replaced by a serine in the Z95 sequence in 72% of the NPC biopsies from European and North African patients. The Zser206 variant is found in a significantly lower percentage (p < 0.001) of other EBV-positive tissues from individuals in the same region (10-33%). In contrast, a 30-bp deletion is observed near the 3' end of the LMP1 gene in the majority of EBV (86%) from NPC and peripheral-blood cells from Asians, whereas a significantly lower percentage (p < 0.001) of NPC biopsies from European and North African patients (56%) have this deletion, as do lymphocytes from control individuals from the same region (36 and 55% respectively).
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PMID:Amino-acid change in the Epstein-Barr-virus ZEBRA protein in undifferentiated nasopharyngeal carcinomas from Europe and North Africa. 946 47


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