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)

In vitro sensitivity of an established cell line from human urinary bladder cancer to various chemotherapeutic agents was determined by 14C-leucine incorporation into the target cells. Of 12 drugs tested, Carboquone, Neocarzinostatin, Actinomycin D, Adriamycin, Mitomycin C and Chromomycin A3 produced intensive cytotoxic effects, while Thio-Tepa, Bleomycin, 5-Fluorouracil and Vincirstine were less cytotoxic, Intravesical instillation of Carboquone, one of the most toxic agents in vitro, resulted in complete or partial tumor remission in 6 of 9 patients with bladder cancer. Prophylactic effects of periodic intravesical Carboquone were also indicated in 7 of 8 patients who had experienced recurring superficial bladder tumors.
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PMID:Chemosensitivity of human bladder cancer cells in long-term culture and clinical responses to the selected anticancer drug. 45 64

About half the mice administered a lethal inoculum of L1210 leukemia become 60-day survivors when treated with an appropriate dose of melphalan. Leucine completely abolishes this long-term survival by interfering with melphalan uptake into the tumor cells. L-alpha-Amino-gamma-guanidinobutyric acid, the lower homolog of arginine, promotes melphalan uptake in vitro only in the presence of leucine. When administered to mice with melphalan and a dose of leucine which negates the 50% cure rate of melphalan, it reduces the therapeutic interference of leucine. However, L-alpha-Amino-gamma-guanidinobutyric acid alone does not improve melphalan therapy, suggesting that endogenous leucine can play only a minor role in interference with therapy of the L1210 leukemia.
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PMID:Effect of L-alpha-amino-gamma-guanidinobutyric acid on melphalan therapy of the L1210 murine leukemia. 45 72

In rats with transplantable mammary or hepatic tumors, plasma ceruloplasmin oxidase activity was increased 50--200%. This occurred progressively with tumors weighing 0.3% of body weight of more, and did not occur upon sham operation or implantation of normal tissue. Incorporation of [3H]-leucine indicated a specific enhancement of ceruloplasmin synthesis in the tumor-bearing rats, and a greater state of activation of the enzyme was also observed. The mechanism of the increase in ceruloplasmin levels in rats and humans with cancer thus appears to involve increased synthesis and activation of the enzyme.
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PMID:Ceruloplasmin elevation and synthesis in rats with transplantable tumors. 45 40

A high molecular weight (greater than 400,000) protease active with [3H]leucine-labeled globin has been found in the postmicrosomal fraction of mouse kidney, brain, heart, spleen, and tumor cells and is most active in liver. The presence in liver was unexpected because liver cytosol is very ineffective in the breakdown of endogenous, labeled proteins. The enzyme has a number of properties that distinguish it from known cathepsins in addition to its high molecular weight. It is most active at pH approximately 7.5. When purified, it is unstable above 20 degrees C and is stabilized by metal chelating agents such as citrate, creatine-P, and glycerate-3-P. It is an -SH protease, but its thermal instability is not affected by 1 mM dithiothreitol. The enzyme is not lysosomal.
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PMID:A high molecular weight protease in liver cytosol. 46 13

In a previous paper, we reported that various D-amino acids were taken up several times more effectively than the corresponding L-isomers into several tumors tested in vivo. In order to investigate this further, the in vitro uptake of D-[14C]leucine by Ehrlich ascites tumor cells was investigated in comparison with that of L-[14C]leucine. The distribution ratio, the effects of amino acids and pH, and an approximately linear Lineweaver-Burk plot indicated that D-leucine was transported by an active transport system for L-leucine. Vmax and ku, the first-order rate constant for the unsaturable component, for the uptake of D- and L-leucines decreased with a fall in temperature. The activation energies for Vmax and ku were in the range of 5-10 and 18-21 kcal/mol, respectively. The values for L-leucine were greater than those for D-leucine. Km for D-leucine transport increased with decreasing temperature, whereas Km for L-leucine decreased. This difference suggests that the large alkyl chains of D- and L-leucines bind to different portions of a carrier protein.
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PMID:Characteristics of D-leucine uptake by mouse Ehrlich ascites tumor cells. 47 35

Amino acids are incorporated at increased rates into hepatic proteins in tumor-bearing humans and animals. In this study, we hoped to elucidate whether this is an expression of increased hepatic protein synthesis or altered isotope dilution in the precursor pool(s). Liver tissue from sarcoma-bearing mice (MCG 101) showed increased specific activities of arginine and leucine in hepatic proteins after i.p. injection of these precursors. The specific radioactivity of leucine in the free amino acid incorporation rate into proteins was also found in incubated liver slices and in a cell-free system of incubated free and membrane-attached polysomes. The increased amino acid incorporation was the net result of increased as well as decreased relative turnover of various hepatic proteins. The hepatic content of RNA was increased, but hepatic DNA and protein content was unchanged in tumor-influenced livers. Increased amino acid incorporation into hepatic proteins in tumor-bearing animals and also probably in cancer patients is due to a net increased hepatic protein synthesis, probably not confined to acute-phase reactants only.
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PMID:Protein synthesis in liver tissue under the influence of a methylcholanthrene-induced sarcoma in mice. 49 94

A microcytotoxicity assay for the detection of complement-dependent serum toxicity against adherent cells has been modified to include post-labeling of the target cells with [3H]leucine or [3H]thymidine. The adaptation represents a significant improvement over the visual counting of residual cells. The technique is more objective and less tedious than the original procedure, while retaining the features of economy of cells and sera, reproducibility, and sensitivity. Examples are given which demonstrate the suitability of the modified assay for the analysis of human and mouse tumor antigens using autologous, allogeneic, and syngeneic sera.
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PMID:A sensitive assay for the detection cytotoxic antibodies to mammalian cell surface antigens. 51 62

Melphalan uptake by L1210 leukemia cells obtained from tumor bearing mice is reduced to one-third of control by physiological concentrations of L-leucine. Kinetic analysis revealed that melphalan and leucine compete for transport carrier sites. Administration of leucine with optimal therapeutic doses of melphalan to tumor bearing mice negated the efficacy of the drug.
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PMID:Amino acid conferred protection against melphalan interference with melphalan therapy by L-leucine, a competitive substrate for transport. 54 13

Plasma membranes, isolated from Ehrlich ascites tumor cells, were dissolved in 2% cholate, 4 M urea and then reformed into liposomes upon dialysis at 4 degrees with exogenous phospholipids. Reconstituted vesicles regain the ability to transport amino acids. Na+ was shown to accelerate the uptake of alpha-aminoisobutyrate, phenylalanine, and methionine, but not leucine or epsilon-aminohexanoic acid. With the reconstituted vesicles, methionine, but not leucine, inhibited the uptake of alpha-aminoisobutyrate. An apparent Km value for alpha-aminoisobutyrate uptake of 3.0 mM was obtained. This value is close to that observed with the intact cells and the native membrane vesicles. A Na+ gradient (high Na+ outside) increased alpha-aminoisobutyrate uptake, whereas a reversed gradient (high Na+ inside) increased alpha-aminoisobutyrate efflux. The latter flux was increased by valinomycin, suggesting electrogenic transport. A modest extent of coupling between a Na+ gradient and uphill flow of alpha-aminoisobutyrate was observed.
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PMID:Sodium-dependent amino acid transport in reconstituted membrane vesicles from Ehrlich ascites cell plasma membranes. 56 50

Melaphan, L-phenylalanine mustard, is transported by the L1210 cell through carriers of the leucine (L) type. Its initial rate of transport is inhibited by both L-leucine, a naturally occuring L system amino acid and 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), A SYNTHETIC AMINO ACID WHICH IS TRANSPORTED BY THE L system in the Ehrlich ascites tumor cell. Both amino acids inhibited melphalan transport comparably in sodium-free medium. However, BCH, in medium containing sodium, was unable to reduce a component of melphalan transport which was readily inhibited by leucine but not by alpha-aminoisobutyric acid. Inhibition analysis indicated that leucine competes with BCH for transport but that a portion of leucine transport is not readily inhibited by BCH. These results suggest that in the L1010 cell melphalan is transported equally by a BCH-sensitive, sodium-independent L system and a BCH-insensitive, sodium-dependent L system.
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PMID:Cytotoxicity as an indicator for transport mechanism: evidence that melphalan is transported by two leucine-preferring carrier systems in the L1210 murine leukemia cell. 56 3


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