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)

Microwave-induced emission spectrometry combined with gel-exclusion chromatography provides a microanalytical system capable of precisely measuring 10 minus 10 to 10 minus 13 g of metal in microgram amounts of enzyme. Such sensitivity greatly exceeds that of other, more conventional methods. Metal quenching agents and low-molecular-weight protein contaminants were removed from the enzyme by Sephadex G-100 chromatography in microbore columns (0.03 times 25 cm). Droplet fractions were analyzed for zinc by the present method, for enzyme activity, and for protein content. With this analytical system we could demonstrate that stoichiometric amounts of zinc are present in the RNA-dependent DNA polymerase, the reverse transcriptase, from wooly monkey type C RNA tumor virus. The precision of the method for zinc was demonstrated by the coefficient of variation of 4.4 percent for 10 mug of zinc per liter. Validity and accuracy of the method were established by determining zinc in a series of zinc metalloenzymes of known metal content and stoichiometry.
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PMID:Microanalytical system for determination of picogram quantities of metals in metalloenzymes, as illustrated with zinc-containing enzymes. 4 97

DNA polymerase from RNA tumor viruses ("reverse transcriptase") has been analyzed for activities which have been associated with other DNA polymerases. Homogeneous DNA polymerase from avian myeoblastosis virus catalyzes pyrophosphate exchange and pyrophosphorolysis. Pyrophosphate exchange is dependent on a template and is base-specific. With avian myeloblastosis virus DNA polymerase, ribonucleotide templates are more efficient for synthesis while deoxyribonucleotide templates are more effective for pyrophosphate exchange. Synthesis, pyrophosphate exchange, and pyrophosphorolysis were inhibited by the chelating agent 1,10-phenanthroline, suggesting that enzyme-bound zinc is required for each of these reactions. The pyrophosphate exchange reaction was also demonstrated with the DNA polymerase from a mutant of Rous sarcoma virus that possesses a temperature-sensitive DNA polymerase. The pyrophosphate exchange reaction with the mutant polymerase is temperature-sensitive which demonstrates that pyrophosphate exchange is indeed catalyzed by the viral DNA polymerase and that the same mutation effects both DNA polymerase and pyrophosphatase activity. Unlike Escherichia coli DNA polymerase I, the DNA polymerase from avian myeloblastosis virus fails to degrade polydeoxyribonucleotides or to convert deoxynucleoside triphosphates into monophosphates. This lack of hydrolytic activities in avian myeoblastosis DNA polymerase should facilitate kinetic studies on the mechanism of DNA synthesis by this enzyme.
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PMID:On the fidelity of DNA replication. Enzyme activities associated with DNA polymerases from RNA tumor viruses. 5 14

Bleomycin serves as a useful prototype for a study of the various properties required in a radiopharmaceutical for tumor imaging. Both in vitro and in vivo results using bleomycin labeled with a large number of different radionuclides have now been reported. In general, it has not been possible to predict in vivo biologic behavior solely from in vitro data. For example, 57Co-bleomycin and 111In-bleomycin both have identical patterns in several different chromatographic systems and do not break down with prolonged storage in saline, exposure to heat, or other cations. However, when the labeled bleomycin is exposed to serum transferrin (and to other as yet unidentified ligands in the body) a difference in stability becomes obvious. The stability and biologic activity of 57Co-bleomycin in humans demonstrate the validity of metal chelation as a labeling technique for this specific molecule, and also suggests that other stable chelates will have useful applications. Although 57Co-bleomycin has the most desirable biologic characteristics of all the chelates of bleomycin, the extremely long physical half-life of 57Co of 270 days creates a significant contamination problem in the hospital. Because of this, the use of 57Co-bleomycin is limited to a few specialized centers. All users have emphasized the need for a better radionuclide to produce a labeled bleomycin with the same or superior biologic characteristics to 57Co-bleomycin. Unfortunately, the elements forming the most stable chelates with bleomycin (copper, zinc, cobalt, and nickel) do not have radionuclides with suitable physical characteristics for scanning. Copper-67 may become available in the future from high-energy linear accelerators. However, even if it were available, copper will probably not have as good chemical properties as cobalt.
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PMID:Radiolabeled antitumor agents. 6 1

Zinc, testosterone and dihydrotestosterone concentrations have been measured in normal prostatic tissue and in specimens obtained from untreated patients with benign prostatic hyperplasia (BPH) and carcinoma of the prostate (CaP). The metal--androgen relationship was examined and related to the pathological condition of the patients. The evidence suggests that discriminant analysis combining the hormonal data into a single variable is a reliable test for distinguishing between BPH and CaP patients. We have observed that the high Zn values found in BPH specimens were always associated with a DTH:T ratio greater than 1. Androgen tissue ratios less than 1 were characteristic of all CaP specimens, and these were usually preceded by a reduction in prostatic Zn concentration. Since these patterns, particularly those associated with neoplasia, precede the clinical manifestations, they may be used as an index for predicting the onset of carcinoma in the prostate gland. They may also be of value in monitoring the progress of the disease.
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PMID:Cancer of the prostate: early diagnosis by zinc and hormone analysis? 8 14

Changes in serum zinc and copper levels were studied in 19 tumor bearing patients undergoing parenteral nutrition (TPN) for five to 42 days. Before initiation of intravenous feeding mean serum zinc and copper concentrations were within normal limits but during TPN levels decreased significantly below those measured prior to parenteral nutrition. During TPN nitrogen, zinc, and copper intake, urinary output and serum levels were studied prospectively in nine of these patients. These nine patients exhibited positive nitrogen retention based upon urinary nitrogen excretion, but elevated urinary zinc and copper excretion and lowered serum zinc and copper concentrations. Neither blood administration nor limited oral intake was consistently able to maintain normal serum levels of zinc or copper. Zinc and copper supplementation of hyperalimentation fluids in four patients studied for five to 16 days was successful in increasing serum zinc and copper levels in only two. The data obtained suggest that patients undergoing parenteral nutrition may require supplementation of zinc and copper to prevent deficiencies of these elements.
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PMID:Abnormalities of zinc and copper during total parenteral nutrition. 10 6

The cytotoxic properties of a bis(thiosemicarbazonato) cadmium complex are studied. Preincubation of Ehrlich cells with the complex prevents growth of the ascites tumor in mice. Although the complex inhibits tumor growth without undue initial toxocity, longer-term side effects limit the use of the compound. The complex inhibits incorporation of 3H-thymidine into DNA and the respiration of tumor cells. It is shown in the principal correlation that the complex is more inhibitory of the above biochemical processes than cadmium ion at equal cellular concentrations of the metal. In addition the cellular reactions of the cadmium, zinc, and copper bis(thiosemicarbazonato) complexes are compared. It is shown that subtle chemical differences in their chelate structures appear to be responsible for their marked differences in cellular reactivity.
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PMID:Reactions of 3-ethoxy-2-oxobutyraldehyde bis(N4-dimethylthiosemicarbazonato) cadmium with tumor cells. 15 45

Cadmium, zinc, copper levels and zinc-copper, zinc-bromine, iorn-zinc, iron-copper and iron-bromine ratios are measured in neoplastic and normal kidney samples from humans by the particle induced X-ray emission analysis (PIXE) technique. It is found that cadmium which is normally present in the tubular cells of kidney is not detectable in tumor samples. It is also observed that the zinc-copper ratios in all neoplastic kidney tissues are decreased, but this observation cannot be extended to other element ratios.
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PMID:Trace element concentrations in renal cell carcinoma. 21 75

Serum copper level (SCL), serum zinc level (SZL), and SCL/SZL ratio were measured in 18 patients with biopsy-proven osteogenic sarcoma. Measurements were made on sequentially collected serum samples beginning prior to the institution of therapy and continuing periodically until documented relapse. All patients were treated by curative resection and adjuvant therapy consisting of high dose methotrexate (with leucovorin rescue) with or without BCG immunotherapy. The SCL, SZI, and SCL/SZL determinations were made using proton-induced x-ray fluorescence spectrometry. SCL was significantly elevated (p less than .0001) in the 18 patients with primary untreated osteogenic sarcoma )173 +/- 30 microgram/dl) compared with a sex and age-matched normal group (115 +/- 16 microgram/dl). A significantly different SZL was not found, however, so that an elevated SCL/SZL ratio in the osteogenic sarcoma patients was primarily due to the altered SCL. SCL and SCL/SZL did not change significantly following curative surgery or become more abnormal in those patients who developed recurrent disease. The SCL and SCL/SZL were noted to be markedly elevated in those patients receiving BCG therapy, raising concern regarding the specificity of these tests as markers of tumor activity. SCL, SZL, and SCL/SZL did not appear useful as markers of tumor activity in patients with osteogenic sarcoma.
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PMID:Serum copper and zinc measurement in patients with osteogenic sarcoma. 30 81

Several immunologic features were analyzed in mice on a zinc-deficient diet [Zn(-)], in mice pair-fed a diet containing zinc [Zn(+)], in mice fed a Zn(+) diet ad lib, and in mice fed laboratory chow ad lib. When placed on a Zn(-) diet, 6- to 8-week-old A/Jax, C57BL/Ks, and CBA/H mice showed loss of body weight, low lymphoid tissue weight, and profound involution of the thymus within 4-8 weeks after initiation of the regimen. Approximately 50% of the mice on the Zn(-) diet developed severe acrodermatitis enteropathica (lesions on tail and paws) and diarrhea. Pair-fed mice on the Zn(+) diet did not show any of these symptoms. Mice on the Zn(-) diet showed the following immune deficiencies: (i) depressed plaque-forming cells against sheep erythrocytes after in vivo immunization; (ii) depressed T killer cell activity against EL-4 tumor cells after in vivo immunization; and (iii) low natural killer cell activity. However, antibody-dependent cell-mediated cytotoxicity against chicken erythrocytes was normal in the mice on the Zn(-) diet. Deficiency of T killer cell activity was not observed when immunization with EL-4 allogeneic lymphoma cells was carried out in vitro. Progressive loss of relative and absolute number of Thy 1.2+ cells and a proportionate relative increase in cells bearing Fc receptors was seen in spleen and lymph nodes of Zn(-) animals. It appears that zinc is an essential element for maintenance of normal T cell and other immune functions in vivo.
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PMID:Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice. 31 74

Preliminary indirect immunofluorescence studies on the zinc glycinate marker (ZGM) were compared with carcinoembryonic antigen (CEA) immunofluorescence, ZGM, detected in 26 of 29 human colon adenocarcinomas, was associated with the epithelial component of the malignant glands. Fluorescence was generally less strong and more granular for ZGM than for CEA and was found in intraglandular spaces, luminal border areas, and cytoplasm. ZGM concentration and tissue localization appeared to be related to tumor differentiation. ZGM was also detected in benign colon mucosae (adjacent to and distant from the carcinomas) from patients with colon carcinoma, but differed from CEA in that it was present in the deep crypt portion only. Gastric, pancreatic, esophageal, and anal adenocarcinomas, as well as benign gastric pyloric and small bowel mucosae had detectable ZGM. CEA, but not ZGM, was observed in 20 nongastrointestinal carcinomas to date. Studies are under way to determine whether ZGM is a marker associated with colon and gastrointestinal adenocarcinoma specifically or undifferentiated crypt cells of the colon and digestive tract in general.
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PMID:Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. II. Immunofluorescence microscopy. 34 70


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