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

Activities of various hydrolytic enzymes were determined in rat organ homogenates and on the surface of cells from various sources, i.e., tumor cell strains, primary cultured cells, normal cells, and their transformants. Alanine, leucine, methionine, phenylalanine, and glycyl-proline aminopeptidases and esterase showed relatively high activities in all these organs and cells. In the kidney homogenate the aminopeptidase A activity was higher in other organs; i.e., the aminopeptidase A activity was lower than that of aminopeptidase B. Normal cells derived from kidneys showed the kidney-type pattern of amino-peptidases A and B on the surface of cells, whereas tumor cells from various origins were of another organ type. When cultured mouse fibroblast strain C3H2K and rat fibroblast strain 3Y1 cells were transformed by SV40 or by a ts A mutant and maintained at permissive temperature, aminopeptidase A activity was drastically decreased, and the ratio of aminopeptidase A to aminopeptidase B was reduced to the levels of tumor cells. If the ts A mutant-transformed cells were grown at the restrictive temperature, the ratio approached that of normal cells. In normal cells, however, cultivation at high or low temperature did not cause any change of the activities.
 ...
PMID:Aminopeptidase activities on the surface of mammalian cells and their alterations associated with transformation. 21 Sep 41

In 22 patients with chronic pancreatitis and 16 patients with pancreas neoplasms gamma-glutamyltranspeptidase (GGTP) and alanine arylamidase (AAP) in serum were measured and the isoenzymes were determined by gel electrophoresis on Agar. No specific isoenzyme pattern was found for chronic pancreatic diseases in a comparative investigation with a group of 19 patients suffering from hepatobiliary diseases. Two fractions of AAP and GGTP isoenzymes were found on agar gel electrophoresis: alpha-1 and alpha-2 (GGTP between alpha-2 and beta-globulin). The alpha-1 fraction of AAP and GGTP seems to be a specific liver isoenzyme. The slower fraction of both enzymes was also found in chronic pancreatic diseases and cholestatic diseases as in neoplasms of liver, pancreas and biliary tract. Practical importance of the findings is diminished by large variation coefficients of the results. A significantly low ratio of alpha-1 to alpha-2 fraction (or beta-globulin) on electrophoresis of the isoenzymes of AAP and GGTP was found in the group with neoplasm of pancreas (especially neoplasm of the pancreas head) as compared to the group with intrahepatic cholestasis. The possible causes and diagnostic importance of the findings are discussed.
 ...
PMID:[Isoenzymes of alanine arylamidase (AAP, EC 3.4.11.2) and gamma-glutamyltranspeptidase (GGTP, EC 2.3.2.2) in chronic pancreatitis and pancreas neoplasm (author's transl)]. 23 68

Macromomycin (MCR), a polypeptide antibiotic previously shown to have antitumor activity in experimental tumors, has been purified into an electrophoretically homogeneous component with an approximate molecular weight of 12,500. MCR has alanine as an NH2-terminal amino acid, 4 cysteine residues, and no arginine or methionine residues. With a fluorescence assay and agarose gel electrophoresis, MCR was shown to induce strand breaks in PM2 DNA in vitro. 2-Mercaptoethanol inhibited the DNA cleavage activity of MCR. When incubated with Novikoff hepatoma ascites cells in tissue culture, MCR caused Novikoff hepatoma ascites cell DNA degradation as observed by the slower sedimentation of DNA on alkaline sucrose density gradient centrifugation when compared to untreated cell DNA. DNA synthesis in Novikoff hepatoma ascites cells was inhibited by 80% after a two-hr treatment with MCR (0.03 microgram/ml). RNA and protein syntheses were inhibited by 25 and less than 10%, respectively, at this concentration of drug. At a concentration of MCR (1.0 microgram/ml), syntheses of DNA and RNA in Novikoff hepatoma ascites cells were totally inhibited. The results of this study suggest that MCR may inhibit tumor cell growth by causing DNA breakage with subsequent inhibition of DNA and other macromolecule syntheses.
 ...
PMID:Purification and mechanism of action of macromomycin. 42 Dec 1

The L-cyst(e)ine requirements of normal and malignant cells are reviewed and expanded within the context of establishing whether the measurement of gamma-cystathionase levels constitutes a predictive test for tumor sensitivity to L-cyst(e)ine depletion. The ability of both purified L-cysteine desulfhydrase and gamma-cystathionase to inhibit the growth of the L-cystine-dependent L1210 leukemia in culture is presented, as well as approaches to circumvent the limitations of these enzymes for in vivo therapy. The ability of proparagylglycine to inhibit L-cysteine biosynthesis in vivo is reviewed for its possible use in combination therapy. In addition, the ability of poly D,L-alanine modification of Escherichia coli L-asparaginase to increase the plasma half-life in mice tenfold as well as to decrease the immunogenicity of the enzyme is presented.
 ...
PMID:L-cyst(e)ine requirements of malignant cells and progress toward depletion therapy. 46 47

Cells separated by enzyme treatment of the R3230AC mammary carcinoma were used to characterize the entry of proline. These cells showed minimal changes in cell viability and intracellular volume and were found to be suitable for transport studies, since the vi of proline was maintained for at least 4 h when cells were stored at 37 or 4 degrees C, or when transport was measured in the presence or absence of Na+. Proline was acitvely transported by these tumor cells, reaching a distribution ratio ([proline] intracellular/[proline] extracellular) of 20 after 2 h. Proline entry consisted of two processes, one saturable (carrier mediated) and the other, non-saturable. The carrier-mediated entry, Km - 0.83 mM and V = 151.10(-5) mumol/min per 5.10(6) cells, was Na+-dependent, sensitive to pH and metabolic inhibitors, and completely inhibited by alpha-(methylamino)-isobutyric acid (Ki = 0.34 mM). Proline entry in the absence of Na+ was 20% that in the presence of Na+ and was found to be due to a non-saturable process, since (a) vi of proline uptake in the absence of Na+ increases linearly with increasing proline concentration and (b) was not suppressed by either 20 mM alpha-(methyl-amino)-isobutyric acid, 50 mM glycine +20 mM phenylalanine, or 50 mM serine +20 mM phenylalanine when proline uptake was measured in the presence or absence of Na+. Therefore, under the conditions studied, we conclude that proline transport appears to be restricted to the A (alanine-preferring) system. Furthermore, these cells should provide a suitable model to study the effect of hormonal manipulations on the amino acid transport process.
 ...
PMID:Characteristics of proline transport into R3230AC mammary tumor cells. 63 48

In order to acquire a fundamental knowledge for the development of better tumor-scanning agents, the in vivo incorporation pattern of three 14C-labeled D-amino acids, alanine, leucine, and tryptophan, into the tumor cells and organs of animals bearing Ehrlich mouse tumor, sarcoma-180, leukemia L-1210, or Yoshida sarcoma was investigated, and compared with that of the corresponding L-forms. The radioactivity of D-amino acids tested was most highly found in tumor cells and pancreas, and the activity in tumor cells was several times higher than that of L-forms. A large portion of the radioactivity of D-forms was found in trichloroacetic acid-soluble fraction of the cells, whereas that of L-forms was mostly in protein fraction, except L-alanine. Although the mechanisms whereby the radioactivity of D-amino acids was concentrated more than that of L-forms in the tumor cells have not yet been clearly elucidated, it was concluded that gamma-emitter-labeled D-amino acids themselves or their derivatives might be useful as tumor-detecting radiopharmaceuticals.
 ...
PMID:Preferential incorporation of some 14C-labeled D-amino acids into tumor-bearing animals. 71 Aug 3

Hepatocytes isolated from adult rat liver by enzymatic dispersion were used to investigate amino acid transport. Steady state and influx experiments were carried out with alpha-amino[1-14C]isobutyric acid and [1-14C]cycloleucine in the presence and absence of sodium under various experimental conditions. Hepatocytes concentrated alpha-aminoisobutyric acid to a 3-fold higher degree than cycloleucine. At low external alpha-aminoisobutyric acid levels (2 to 5 mM), about 25% and 75% of entry were accounted for by nonsaturable and saturable processes, respectively. The nonsaturable component was sodium-independent, and had the properties of passive diffusion. The saturable transport was dependent on external sodium; the rate of transport reached its maximal value with sodium greater than or equal to 75 mM. Sodium increased the apparent Vmax of transport without changing the apparent Km. This component was largely dependent on energy supplies and was strongly reduced at pH less than or equal to 6.5. The value for activation energy (Ea approximately equal to 15 kcal/mol, calculated from the Arrhenius plot) favors a mediated active transport. The Na+-dependent influx of alpha-aminoisobutyric acid was competitively inhibited by N-methyl-alpha-aminoisobutyric acid (Ki approximately equal to 9.3 mM) and alanine (Ki approximately equal to 2 mM) to the extent of 70% and 100%, respectively. The N-methyl-alpha-aminoisobutyric acid-sensitive part of alpha-aminoisobutyric acid influx represents transport through the "A" system, whereas the N-methyl-alpha-aminoisobutyric acid-insensitive part of transport is believed to occur through the "ASC" system. No evidence was obtained to suggest that alpha-aminoisobutyric acid is transported by the "L" system. Cycloleucine transport was a composite phenomenon involving at least two saturable processes, one of which was sodium-dependent and inhibited by alpha-aminoisobutyric acid, and probably represents entry through the A and ASC systems. The sodium-independent component was completely and competitively inhibited by 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (Ki approximately equal to 2 mM). This component exhibited accelerative exchange-diffusion and was pH-insensitive, properties which suggest a facilitated diffusion process. However, the weak inhibition exerted by oligomycin and cyanide along with the concentrative effect observed indicated that uphill transport was also operative. These data are in good agreement with those reported for the L system. We conclude that, as in Ehrlich ascites tumor cells and in embryonic heart cells, the A, ASC, and L systems are operative in isolated hepatocytes for the transport of amino acids.
 ...
PMID:Neutral amino acid transport. Characterization of the A and L systems in isolated rat hepatocytes. 83 14

Activities of hydrolytic enzymes on the surface of monkey kidney, canine kidney, L. FM3A and various tumor cells were determined and compared with those in the cell homogenate. Although aminopeptidase (EC 3.4.11.-) activities were always detected on the surface membrane in mammalian cells, trypsin, chymotrypsin and elastase activities were not detected while slight glycosidase activity was detected in a suspension of cultured cells. The activities of alanine-, leucine-, methionine- and phenylalanine-aminopeptidases were rather high but aminopeptidase A, proline-, valine-, glycyl propline dipeptidyl-and glycyl propyl leucine-tripeptidyl-aminopeptidases showed relatively low activities. Aminopeptidase activity was also demonstrated in the isolated membrane fractions. The specific activities of enzymes in these membrane fractions were not significantly greater than in cell homogenate so it was concluded that these enzyme activities were rather loosely bound to the cell membrane. Further evidence for the localization of the aminopeptidase activities on the cell surface was obtained by using glass-bead-bound substrate and detecting the release of the terminal residues. When bestatin, a specific inhibitor against aminopeptidase B and leucine aminopeptidase, was included in the assay system for the enzyme activities on the cell surface, the enzymes were commonly inhibited in all types of cells.
 ...
PMID:Aminopeptidase activities on the surface of mammalian cells. 99 Mar 9

1. The regulatory properties of two interconvertible kinetic forms of class A pyruvate kinase from Ehrlich ascites tumor cells have been studied with a partially purified enzyme preparation free of interfering enzymatic activities. 2. The hyperbolic form shows Michaelis-Menten kinetics for P-pyruvate, with high affinity for this substrate and low affinity for the inhibitory amino acids alanine and phenylalanine. The sigmoidal form displays positive cooperativity respect to P-pyruvate (n=1.4), with lower affinity for this substrate and higher affinity for the inhibitory amino acids. 3. The equilibrium between the hyperbolic and the sigmoidal forms of the enzyme is affected by substraetes and effectors. P-pyruvate, ADP and Fru-P2 shift the equilibrium to the hyperbolic form while ATP, alanine and phenylalanine stabilize the sigmoidal form. 4. Effector metabolites affect the molecular weight of the protein, acting on an equilibrium between dimers and tetramers. P-pyruvate and ADP associate the enzyme to a tetramer while ATP, alanine and phenylalanine favor the occurrence as a dimer. The positive modifier Fru-P2 did not associate the enzyme to the tetramer, even at 1 mM concentration. 5. A tentative molecular model for pyruvate kinase A on the basis of the kinetic and aggregation interconversion is proposed.
 ...
PMID:Interconversion phenomena between two kinetic forms of class a pyruvate kinase from Ehrlich ascites tumor cells. 100 94

Curve-fitting procedures indicated that exo-2-amino-bicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) modified V and Km for one of two systems serving for histidine transport into the S37 ascites tumor cells. When this system was obliterated by leucine in the medium, BCH had no effect on histidine transport. Curve-fitting procedures similarly suggest N-methyl-alpha-aminoisobutyric acid affected the Km and V values for the other histidine-transporting system and that carboxymethylhistidine (His(Cm)) inhibited both transport systems. His(Cm) further inhibited histidine uptake into leucine-inhibited cells. Km and V values were altered simultaneously in the presence of several inhibitory analogs. Alanine methyl ester markedly inhibited high-concentration histidine uptake, whereas leucine methyl ester markedly inhibited low-concentration histidine uptake. The present results confirm earlier suggestions that our high c system is Christensen's A system and our low c system his L system. We also confirm a very high degree of specificity of N-methyl-alpha-aminoisobutyric acid for the A or high c system, and of BCH for the L or low c system. We suggest the utility of combining two approaches to the study of transport system properties; use of specific analogs and modification of biphasic plots. We demonstrate that the carboxyl group is not a prerequisite molecular feature for inhibitory interaction with the A or L system.
 ...
PMID:Biphasic kinetic plots and specific analogs distinguishing and describing amino acid transport sites in S37 ascites tumor cells. 113 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>