Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma amino acid concentrations were measured in fasting nontumor bearing (NTB) and tumor bearing (TB; methylcholanthrene induced sarcoma) male Fischer F344 rats during infusion of 0.9% NaCl solution or glucose at 3.72 or 13.05 mumol/100 g total body weight (TBW)/min. The animals were studied when the tumor comprised only 8% of the TBW at a time when decreased food intake and weight loss were not manifest. During 0.9% NaCl infusion there were no significant differences between NTB or TB animals in the concentration of alanine (NTB: 152.6 +/- 20.1; TB: 150.3 +/- 19.0 microM; mean +/- SD), branched chain amino acids (BCAA) (NTB: 343.3 +/- 48.7; TB: 344.2 +/- 20.5 microM), essential amino acids, aromatic amino acids, or total amino acids. During infusion of glucose at 3.72 mumol/100 g TBW/min the alanine levels rose (NTB: 283.6 +/- 33.4; TB: 286.7 +/- 43.3 microM), and the BCAA levels fell (NTB: 215.9 +/- 19.4; TB: 228.7 +/- 43.4 microM) to similar concentrations in both NTB and TB animals. Glucose infusion at 13.05 mumol/100 g TBW/min resulted in an additional increase in the alanine concentration (NTB: 344.5 +/- 28.7; TB: 382.8 +/- 116.6 microM), and a further decrease in the BCAA concentration (NTB: 166.4 +/- 30.8; TB: 160.7 +/- 30.5 microM) without significant differences between NTB and TB animals. Paired analysis for each animal prior to and during glucose infusion demonstrated a similar absolute micromolar change in alanine and BCAA concentration during both glucose infusion rates in both NTB and TB animals. The levels of aromatic amino acids and total amino acids were unchanged and the essential amino acid concentrations were decreased only at the higher glucose infusion rate in both NTB and TB groups. Basal amino acid metabolism appears similar in the NTB and TB animals, prior to the onset of anorexia and weight loss. During exogenous glucose infusion the reciprocal changes in the plasma alanine and BCAA concentrations support the concept of a glucose-alanine-BCAA cycle at the whole body level that appears to respond to a similar extent in NTB and TB animals.
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PMID:Basal amino acid concentrations and the response to incremental glucose infusion in tumor bearing rats. 390 81

Aspects of the toxicology of N-methylformamide (NMF), an investigational antitumour agent, were studied in mice. After injection of NMF at its LD10 (800 mg/kg) dosage the total peripheral white blood cell and platelet counts were unchanged in BALB/c mice. A mild granulocytosis was seen in this strain after administration of the LD50 (2300 mg/kg) dosage. Plasma activity of the enzyme sorbitol dehydrogenase in BDF1 mice was markedly increased after either a single injection of not less than 800 mg/kg or a chronic treatment of not less than 400 mg/kg/day over 5 days indicating the drug to be hepatotoxic. Plasma activities of L-alanine and L-aspartate aminotransferases were also increased after the chronic treatment. Chronic administration of NMF was less hepatotoxic than single dose administration of the same total dose and also increased the antitumour efficacy of NMF against the M5076 sarcoma. These results indicate that the maximum therapeutic benefit of NMF might be obtained by the use of chronic schedules and that the drug is not myelosuppressive.
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PMID:Studies on the toxicity of the antitumour agent N-methylformamide in mice. 396 88

The DNA fragment encompassing the ras gene of Harvey murine sarcoma virus was sequenced and assigned the coding region of a transforming protein, p21, to the sequence. Examination of nucleotide sequence, taken together with the result of analysis of the ras mRNAs (1), has revealed that p21 is encoded from a continuous coding region starting with the 5' proximal initiation codon but not a processed protein. However, there were found several differences between the sequence published by Dhar et. al. (2) and ours, including 9 deletions, 7 substitutions and 2 insertions of nucleotides in the published sequence of 997 nucleotides in length. Among these, one of the substitutions occurring in the coding region resulted in amino acid replacement of glycine by alanine at position 122 of p21. The evidences are presented with some of actual gel autoradiographs.
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PMID:An altered DNA sequence encompassing the ras gene of Harvey murine sarcoma virus. 608 92

In this paper the synthesis of the following elongated tuftsin analogs: Thr-Lys-Pro-Lys-Thr-Lys-Pro-Lys (I), Thr-Lys-Pro-Lys-Thr-Lys-Pro-Arg (II) and Ala-Lys-Thr-Lys-Pro-Arg-Glu-Gln (III) by the classical method is described. The compound II markedly inhibited the growth of murine sarcoma viruses (MSV).
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PMID:Synthesis and biological investigations of new tuftsin analogs with elongated peptide chain. 631 64

The 21,000-dalton protein (p21) encoded by the ras oncogene of Harvey murine sarcoma virus (v-Ha-ras) becomes phosphorylated (pp21) in vivo and in vitro on threonine residue 59. p21 molecules encoded by cellular ras genes (c-Ha-ras-1) contain an alanine at position 59, and thus these p21 molecules are not phosphorylated. In this investigation, recombinant ras genes have been constructed between the 5' p21 coding region of normal (EC) or oncogenically activated (EJ) human c-Ha-ras-1 and the 3' p21 coding region of v-Ha-ras to generate p21 molecules containing a threonine phosphoacceptor site at position 59 and a glycine (EC/v-Ha) or valine (EJ/v-Ha) at residue 12. In transformed NIH 3T3 mouse fibroblast cells labeled with [35S]methionine, the ratio of pp21 to p21 was strikingly modulated by the amino acid at residue 12. v-Ha-ras p21 has an arginine at position 12, and 24% of total p21 was in the phosphorylated form. A glycine at residue 12 decreased the amount of pp21 to 14% of total p21, and a valine at residue 12 dramatically increased this value to 50%. In vitro, the valine form of p21 had 2.4- and 2.7-fold greater autophosphorylating activity than the glycine and arginine forms of p21, respectively, using [gamma-32P]GTP as phosphate donor, but the three p21 species had similar Km values for GTP (0.20-0.27 microM). These results indicate that a biochemical activity of p21 distinguishes between previously observed biological differences of normal and activated human ras genes.
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PMID:Autophosphorylation of v-Ha-ras p21 is modulated by amino acid residue 12. 660 66

The increased energy expended by the host to synthesize substrate, which is utilized by the tumor, is a potential cause of cancer cachexia. In vivo glucose and alanine kinetics were examined by tracer methodology in a sarcoma-bearing rat model. The effects of 3-mercaptopicolinic acid, a potent inhibitor of gluconeogenesis, was also examined on this model. Both tumor-bearing (TB) and nontumor bearing (NTB) animals were gaining weight prior to study and the tumors were relatively small. The TB animals had significantly lower plasma glucose and higher blood lactic acid levels compared with NTB animals. After inhibition of gluconeogenesis, the plasma glucose decreased and the blood lactate increased significantly more in TB than NTB animals. The glucose turnover rate was significantly greater in TB compared with NTB animals, as was the rate of glucose recycling and the rate of gluconeogenesis (alanine leads to glucose), both energy demanding processes. These results suggest that the tumor-bearing animal, even prior to significant cachexia, has an excess demand for energy, the provision of which may be a significant factor in malignant cachexia.
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PMID:Metabolic alterations in a noncachectic animal tumor system. 722 7

One hundred ten primary hepatic neoplasms, excluding hematopoietic and vascular tumors, were diagnosed in 12,245 canine necropsies. Included were 55 hepatocellular carcinomas, 24 bile duct carcinomas, 2 combined hepatocellular and cholangiocarcinomas, 15 carcinoids and 14 sarcomas. A majority of the dogs with hepatocellular carcinoma (80%), bile duct carcinoma (65%) and sarcoma (61%) were 10 years old or older; 71% of the dogs with carcinoid were under 10 years old. Hepatocellular carcinoma and sarcoma occurred more often in males, bile duct carcinoma in females, and no sex predisposition was found in dogs with carcinoid. All dogs had hematologic and biochemical abnormalities relating to liver function. The aspartate amino transferase/alanine amino transferase ratio was less than one in cases of hepatocellular carcinoma and bile duct carcinoma, and more than one in cases of carcinoid and sarcoma. A massive lesion in one of the liver lobes was the most common gross morphologic feature in cases of hepatocellular carcinomoa and bile duct carcinoma, with the left lateral lobe affected most often. In cases of carcinoid, most of the lesions were diffuse. The most common sites of metastases were lymph nodes and lungs for hepatocellular carcinoma and bile duct carcinoma, lymph nodes and peritoneum for carcinoid, and spleen for sarcoma.
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PMID:Canine hepatic neoplasms: a clinicopathologic study. 740 66

Alanine chloromethylketone and leucine chloromethylketone were synthesized and their effects on amino acid transport in sarcoma 37 mirone ascites tumor (S37) cells were studied. Alanine chloromethylketone preincubation weakly inhibited system A. Leucine chloromethylketone preincubation strongly inhibited both amino acid transport systems L and A. Leucine chloromethylketone was also a competitive inhibitor of leucine transport. Labeled leucine chloromethylketone was concentrated by S37 cells. Leucine chloromethylketone preincubation inhibition was concentration dependent and partial protection of transport was afforded by leucine. Steady-state retention of amino acids was decreased more than the initial velocity of transport by leucine chloromethylketone preincubation. Glutathione was also depleted. Labeled leucine chloromethylketone was incorporated in a plasma membrane protein fraction comigrating on a DEAE-cellulose column (DE52) with gamma-glutamyltranspeptidase activity. There was a modest increase in vital staining after treatment of S37 cells with leucine chloromethylketone, and glucose uptake was also inhibited. Whilst several effects occur during treatment of S37 cells with leucine chloromethylketone, it is suggested than one prominent effect is alkylation of amino acid transport system components.
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PMID:Inhibition of S37 ascites cell amino acid transport systems by alpha-chloromethylketone analogs. 741 42

Systematic replacement of the P4-P2 subsites of substrate-based human immunodeficiency virus type 1 protease (HIV-1 PR) inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere (Cha-psi [H.E.]-Ala) at positions corresponding to the scissile sites of substrates was carried out. The structure-activity relationship revealed that compounds with the combination of hydrophilic P3 and beta-branched hydrophobic P2 amino acids generally showed strong inhibitory activity against HIV-1 PR. In particular, compounds 4 (Boc-Orn-Val-Cha-psi [H.E.]-Ala-NHBun; Bu(n) = n-butyl, Ki = 11 nM) and 6 (Z-Orn-Val-Cha-psi [H.E.]-Ala-NHBun, Ki = 8 nM) exhibited good enzyme selectivity, possessing no significant inhibitory activities toward closely related aspartic proteases, pepsin, cathepsin D, and renin. As a possible model system for (anti-Mo-MSV/MLV complex (Mo-MSV = Moloney murine sarcoma virus; MLV = murine leukemia virus)) activity was investigated. Both compounds were found to inhibit moderately the focus formation of Mo-MSV/MLV complex in NIH3T3 cells (compound 4, IC50 = 1.8 microM; compound 6, IC50 = 1.0 microM).
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PMID:Studies of human immunodeficiency virus type 1 (HIV-1) protease inhibitors. III. Structure-activity relationship of HIV-1 protease inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere. 800 98

Exposure of the gastrin-releasing peptide (GRP) receptor to agonists causes a rapid desensitization of the receptor-stimulated mobilization of intracellular calcium. Homologous desensitization occurs by uncoupling the G-proteins from the receptor and by ligand induced internalization. The molecular determinants of desensitization of the GRP receptor are not well known. The importance of tyrosine 324 which is located in a highly conserved NPX2-3 Y motif of the GRP receptor was investigated. Kirsten murine sarcoma virus-transformed rat kidney (KNRK) cells were transfected with expression vectors encoding either the wild type or the mutant (tyrosine 324 to alanine 324) rat GRP receptor. The wild type and mutant GRP receptors were expressed at a high level in the KNRK cells, 2.0 x 10(6) and 0.5 x 10(6) receptors per cell, respectively. The wild type and mutant GRP receptors bound GRP with the same affinity (Kd = 6-7 nM). KNRK cells expressing the wild type or mutant GRP receptor had similar [Ca2+]i, dose response to GRP. KNRK cells expressing the GRP receptor rapidly internalized bound 125I-GRP at 37 degree C. Internalization was inhibited at 4 degrees C and by 0.45 m sucrose. The internalization of bound 125I-GRP by the mutant GRP receptor was identical to the wild type receptor. Fluorescent microscopy was used to directly observe the GRP receptor expressed on the surface of the KNRK cells and to visualize its ligand induced internalization. There was no difference in the pattern of internalization between the wild type and mutant GRP receptors expressed in KNRK cells. Therefore, the highly conserved tyrosine 324 does not have a role in GRP binding, receptor-G-protein interaction, or initial events of ligand induced receptor internalization. The NPXnY motif is not a general sequestration sequence for seven transmembrane G-protein linked receptors.
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PMID:The conserved NPXnY motif present in the gastrin-releasing peptide receptor is not a general sequestration sequence. 806 19


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