Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A proposed Wilms tumor gene, WT1, which encodes a zinc finger protein, has previously been isolated from human chromosome 11p13. Chemical mismatch cleavage analysis was used to identify point mutations in the zinc finger region of this gene in a series of 32 Wilms tumors. Two exonic single base changes were detected. In zinc finger 3 of a bilateral Wilms tumor patient, a constitutional de novo C----T base change was found changing an arginine to a stop codon. One tumor from this patient showed allele loss leading to 11p hemizygosity of the abnormal allele. In zinc finger 2 of a sporadic Wilms tumor patient, a C----T base change resulted in an arginine to cysteine amino acid change. To our knowledge, a WT1 gene missense mutation has not been detected previously in a Wilms tumor. By comparison with a recent NMR and x-ray crystallographic analysis of an analogous zinc finger gene, early growth response gene 1 (EGR1), this amino acid change in WT1 occurs at a residue predicted to be critical for DNA binding capacity and site specificity. The detection of one nonsense point mutation and one missense WT1 gene point mutation adds to the accumulating evidence implicating this gene in a proportion of Wilms tumor patients.
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PMID:Zinc finger point mutations within the WT1 gene in Wilms tumor patients. 131 72

Sterigmatocystin and aflatoxin are potent mutagens that contaminate foodstuffs stored under conditions that permit fungal growth. These food mycotoxins can be metabolically activated to their epoxides, which subsequently form covalent adducts with DNA and can eventually induce tumor development. We have generated the sterigmatocystin-d(A1-A2-T3-G4-C5-A6-T7-T8) covalent adduct (two sterigmatocystins per duplex) by reacting sterigmatocystin-1,2-epoxide with the self-complementary d(A-A-T-G-C-A-T-T) duplex and determined its solution structure by the combined application of two-dimensional NMR experiments and molecular dynamics calculations. The self-complementary duplex retains its 2-fold symmetry following covalent adduct formation of sterigmatocystin at the N7 position of G4 residues on each strand of the duplex. The H8 proton of [ST]G4 exchanges rapidly with water and resonates at 9.58 ppm due to the presence of the positive charge on the guanine ring following adduct formation. We have assigned the exchangeable and nonexchangeable proton resonances of sterigmatocystin and the duplex in the covalent adduct and identified the intermolecular proton-proton NOEs that define the orientation and mode of binding of the mutagen to duplex DNA. The analysis was aided by intermolecular NOEs between the sterigmatocystin protons with both the major groove and minor groove protons of the DNA. The molecular dynamics calculations were aided by 180 intramolecular nucleic acid constraints, 16 intramolecular sterigmatocystin constraints, and 56 intermolecular distance constraints between sterigmatocystin and the nucleic acid protons in the adduct. The sterigmatocystin chromophore intercalates between the [ST]G4.C5 and T3.A6 base pairs and stacks predominantly over the modified guanine ring in the adduct duplex. The overall conformation of the DNA remains right-handed on adduct formation with unwinding of the helix, as well as widening of the minor groove. Parallel NMR studies on the sterigmatocystin-d(A1-A2-A3-G4-C5-T6-T7-T8) covalent adduct (two sterigmatocystins per duplex) provide supportive evidence that the mutagen covalently adducts the N7 position of G4 and its chromophore intercalates to the 5' side of the guanine and stacks over it. The present NMR-molecular dynamics studies that define a detailed structure for the sterigmatocystin-DNA adduct support key structural conclusions proposed previously on the basis of a qualitative analysis of NMR parameters for the adduct formed by the related food mutagen aflatoxin B1 and DNA [Gopalakrishnan, S., Harris, T. M., & Stone, M. P. (1990) Biochemistry 29, 10438-10448].
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PMID:Solution structure of the covalent sterigmatocystin-DNA adduct. 132 56

In this study a human glioma-derived intracerebral tumor model was analyzed histologically and examined by image-guided 1H NMR spectroscopy. It was shown that histological characteristics such as cellular subpopulation and necrosis of the primary tumor were preserved in the implants. Usually circumscript tumor growth was present with tumor cells invading the surrounding brain parenchyma. It was demonstrated that tumor growth and tumor metabolism could be monitored by image-guided 1H NMR spectroscopy in a longitudinal study. One of the initial changes noticed was the rise of the lactate signal in the tumor region followed by an increase of the choline and a decrease of N-acetyl-aspartate and phosphocreatine signals. Even before tumor invasion in brain adjacent to the central tumor area could be demonstrated by NMR imaging increased lactate and moderately increased choline signals were measured in these regions. By histopathological examination these areas were shown to be infiltrated by single tumor cells. These observations indicate that image-guided 1H NMR spectroscopy could play an important role in the study of brain tumor biology, especially in the case of changing tumor metabolism during growth.
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PMID:Image-guided 1H NMR spectroscopical and histological characterization of a human brain tumor model in the nude rat; a new approach to monitor changes in tumor metabolism. 133 42

Four platinum(II) aminobenzamidine complexes have been prepared and characterized by IR and 1H and 13C NMR spectroscopy, and tested for their ability to interact with the nicked and closed circular forms of the pUC8 plasmid DNA. The results show that the complexes of formula [Pt(LH)2Cl2]2X have a cis- geometry with an amino-Pt bonding, where L is either p- or m-aminobenzamidine and where 2X is 2Cl- or PtCl4(2-). It was observed that these complexes significantly alter the electrophoretic mobility of nicked and closed circular forms of DNA and that the alteration in electrophoretic mobility due to Pt(II)-p-aminobenzamidine binding is higher than that due to Pt(II)-m-aminobenzamidine. No difference in mobility was observed whether the DNA interacted with complexes having as counteranion Cl- or PtCl4(2-). The synthesized compounds were, in addition, assayed for antitumor activity in vitro against colon (CX-1), lung (LX-1), and mammary (MX-1) human tumor cells. The results show that these complexes inhibited the multiplication of the tumor cells and that they show higher specificity for lung cells.
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PMID:Platinum complexes of p- and m-aminobenzamidine. Synthesis, characterization, and cytotoxic activity. 133 5

Human tumor and skeletal muscle tissue was studied by means of in vivo 1H, 31P, and 13C MRS. The examinations were performed with a 1.5 T whole-body MR scanner equipped with a second RF system. Localized 1H and broadband proton-decoupled 31P and 13C MR spectra were obtained in measurement times of 5, 10 and 33 min, respectively, from a malignant fibrous histiocytoma in a patient and from gastrocnemius muscle tissue in healthy volunteers. Proton decoupling enhanced the sensitivity (via the nuclear Overhauser effect) and the information available from in vivo 31P and 13C MR spectra significantly. The most information was obtained from 1H-decoupled 31P spectra. Observation of more than one spin species allows peak assignments to be verified mutually. The spectral data of the histiocytoma differ largely from that of muscle tissue and show a tumor with elevated pH value, normal level of nucleoside 5'-triphosphates, and high level of compounds involved in phospholipid turnover. The multinuclear in vivo MRS experiment may allow the non-invasive observation of almost the complete pathway of phospholipid synthesis and degradation in intact human tissue.
NMR Biomed
PMID:In vivo 1H, 31P-[1H] and 13C-[1H] magnetic resonance spectroscopy of malignant histiocytoma and skeletal muscle tissue in man. 133 60

This study evaluates a number of methods for obtaining 1H NMR spectra with adequate suppression of lipid and water resonances in two subcutaneously implanted transplantable tumor models (RIF-1 and EMT6/SF). Spin-echo spectra with long TEs (270 ms; water suppressed by presaturation) eliminated lipid resonances from 1H spectra of RIF-1 and decreased lipid contamination in spectra of EMT6/SF; however, spectral sensitivity was substantially reduced. A shorter TE (135 ms) increased sensitivity but did not result in adequate suppression of the lipid peaks. In RIF-1, but not EMT6/SF, adequate lipid suppression was achieved by: (i) spatially selective presaturation of lipid, which in this tumor (but not in EMT6/SF) was localized in a thin region along the periphery of the tumor, followed by a 1-D spin-echo chemical shift imaging pulse sequence (TE = 135 ms); and (ii) 2-D spin-echo chemical shift imaging (TE = 270 ms; approximately 2 x 2 x 9 mm3 voxels). Preliminary 1H studies of the RIF-1 tumor indicate that: (i) there are no significant changes in metabolite levels relative to tumor water during 4 days of untreated tumor growth; (ii) tumor response to chemotherapy with 5-fluorouracil results in a decrease in intensity of all metabolite 1H resonances relative to tumor water, with total choline decreasing the most and lactate the least; and (iii) acute tumor blood flow reduction induced by administration of hydralazine results in doubling of the lactate intensity relative to water.(ABSTRACT TRUNCATED AT 250 WORDS)
NMR Biomed
PMID:1H NMR spectroscopy of subcutaneous tumors in mice: preliminary studies of effects of growth, chemotherapy and blood flow reduction. 133 62

Two tumor cell lines (C6 glioma and N1E-115 neuroblastoma), primary glia and primary neurons (from rat) were incubated with 2-13C-pyruvate and 3-13C-pyruvate in culture dishes. 13C NMR spectra of the cell extracts were used to determine the ratio of pyruvate carboxylase to pyruvate dehydrogenase activity. Pyruvate carboxylase activity was found higher in primary glia cells than in neurons. Glial cells synthesized more amino acids, ie, their TCA cycle was used to a larger extent for biosynthesis than is the case of neurons, where it is preferentially used for the energy metabolism.
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PMID:A 13C NMR study on fluxes into the TCA cycle of neuronal and glial tumor cell lines and primary cells. 133 2

Experimental brain tumors produced in rats (n = 10) by stereotactic implantation of cells from the F98 anaplastic glioma clone into the right caudate nucleus were studied in vivo using localized proton NMR and in vitro using high-resolution proton NMR, bioluminescent imaging of lactate, ATP and glucose distributions, and fluorescent imaging of regional pH. In vivo spectra from normal brain contralateral to the tumor regions showed resonances assignable to N-acetyl aspartate (NAA), creatines, choline-containing compounds, myo-inositol, glutamate and glucose in a pattern similar to those obtained from normal anaesthetized rats. In vivo tumor spectra were characterized by the almost complete absence of NAA, a substantial reduction of total creatine and glucose, and an increase of cholines. Based on the in vitro spectra the increase of the myo-inositol signal observed in vivo was mainly attributed to glycine. Histological examination as well as bioluminescent and fluorescent imaging indicated two stages of tumor development, i.e., solid vital tumors and tumors with necrosis. However, there was no consistent relationship between proton NMR observations and tumor development.
NMR Biomed
PMID:Localized proton NMR spectroscopy of experimental gliomas in rat brain in vivo. 133 73

In order to ascertain the antitumor properties of metal complexes, we have investigated their effect on hepatic DNA, RNA pools, and protein levels in rats bearing transplanted tumors by Dalton's Lymphoma cells because antitumor agents are directed against DNA, RNA transcription, and synthesis. These coordination complexes have been synthesized by the condensation of 2,6-diacetylpyridine with FaHh and DAP-Th2, thereafter they were complexed with nickel, cobalt, and iron. The structure of these metal complexes have been elucidated on the basis of IR, UV, NMR, Mass, EPR, and magnetic studies. The tumor-transplanted rats were treated with these metal complexes and ligands (2 ml of 1 mM sol/Kg body weight, s.c.) for two weeks to study their effect on DNA, RNA pools, and protein levels. The metal complexes have altered the hepatic DNA, RNA pools, and protein levels in the liver, kidney, and spleen of rats.
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PMID:Antitumor activity of some metal complexes: effect on hepatic DNA, RNA, and protein synthesis in rats bearing transplanted tumors by Dalton's lymphoma cells. 138 16

The absolute metabolite quantification method of Thulborn and Ackerman [J. Magn. Reson. 55, 357 (1983)] in which the tissue water proton signal is used as an internal intensity standard and its more recent variation in which NMR peak intensities are referenced to that of the natural abundance deuterium signal of water [Li et al., SMRM Abstr. 2, 825 (1988); Song et al., Magn. Reson. Med. 25, 45 (1992) have been implemented to obtain absolute phosphate metabolite concentrations in subcutaneous RIF-1 tumors during untreated growth and following treatment with 5-fluorouracil. The equivalence of these two hydrogen isotopes as intensity standards and the validity of their use in the determination of absolute metabolite concentrations in vivo by NMR has been demonstrated. On matched in vivo and extract tumor samples (n = 5), excellent agreement has been obtained between nucleoside triphosphate concentrations determined by NMR and those derived by HPLC analysis for the control tumors. Following 3 days of untreated growth, absolute concentrations of phosphate metabolites in RIF-1 tumors (n = 10) decreased significantly, except for the Pi concentration which did not vary. For the treated tumors (n = 10) there were no changes in metabolite concentrations except for a decrease in the PCr and, possibly, Pi concentrations. The PCr/Pi ratio in the latter tumors did not change. These observations suggest that changes in absolute metabolite concentrations may be more sensitive indices of response to therapy than changes in metabolite peak amplitude ratios, a parameter commonly used to express in vivo NMR data.
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PMID:Determination of absolute phosphate metabolite concentrations in RIF-1 tumors in vivo by 31P-1H-2H NMR spectroscopy using water as an internal intensity reference. 143 14


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