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

We have previously reported that from 350 amino acid (A-A) derivatives five were selected after the primary in vivo and in vitro screening tests. The five compounds which were found to possess potential antitumor activity against Ehrlich ascites carcinoma are as follows: beta-naphthalene-sulfonyl-DL-tryptophan (A-91), beta-naphthyl-aminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), n-9-fluorenylactyl-L-phenylalanine (A-192), and N-propoinyl-L-valine (A-195). The effect on life prolongation and tumor growth of these selected A-A derivatives against various types of tumors, including ascites and solid tumors in mice and ascites hepatomas in rats, was examined. A-A derivatives were administered once daily 3 consecutive days starting 24 hours after tumor implantation. Experimental results showed that among the five A-A derivatives possessing considerable activity against Ehlich carcinoma, A-144 and A-145 were found to be more effective than chromomycin A and showed activity similar to that of cyclophosphamide against ascites Sarcoma 180. A-A derivatives showed slight antitumor activity against SR61 and L1210 leukemias. In rat ascites hepatoma, such as AH13, AH7974, AH60C, and Yoshida sarcoma, only A-145 showed a significant prolongation of the lifespan in the control groups. The five selected A-A derivatives significantly inhibited the growth of Nakahara-Fukuoka sarcoma and solid Sarcoma 180. These findings indicate that among the five A-A derivatives, A-15 appeared to be the most active against ascites and solid tumors.
 ...
PMID:Antitumor activity of selected amino acid derivatives against various tumor systems. 16 35

Approximately 350 amino acid derivatives were synthesized and tested for antitumor activity in four tumor systems. The effect on life prolongation and tumor growth was examined using mouse leukemia SR-61, Ehrlich ascites carcinoma, ascites sarcoma-180, and rat ascites hepatoma (AH-60C). Among these 350 derivatives, 29 compounds were found to be significantly effective in prolongation of the median life-span and inhibitory effect on tumor growth in the primary screening. Among these 29 compounds, the following five compounds were found to possess potential antitumor activity: N-(2-Naphthalene)sulfonyl-DL-tryptophan (A-91), 2-naphthylaminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), N-9-fluorenylacetyl-L-phenylalanine (A-192), and N-propionyl-L-valine (A-195). These five compounds were active in prolongation of the life-span of mice bearing Ehrlich ascites carcinoma and in the inhibition of the cell growth. Some of these amino acid derivatives inhibited biosynthesis of macromolecules, DNA, RNA, and protein, in tumor cells. These results suggest that the site of action of the five amino acid derivatives appears to result from the inhibition of macromolecules and another unknown mechanism.
 ...
PMID:Antitumor activity of amino acid derivatives in the primary screening. 16 14

Plastic plates implanted subcutaneously to rats induced sarcoma in 11 of 27 animals (40.7%) which survived up to the time of the first tumour appearance (12.3 months). No tumours were revealed at the sites of the plastic powder implantation. Following long-term administration of DL-tryptophan tumours developed around the plates in 6 to 19 rats (31.5%) in 13.8 months, and around the powder in 2 of 5 rats which survived for 18.7 months. Some animals of this group displayed preneoplastic changes around the powder clumps.
 ...
PMID:[Effect of DL-tryptophan on blastomogenesis induced by acrylic plastic]. 69 82

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

Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10(6) methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17-18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor-associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia.
 ...
PMID:The early cancer anorexia paradigm: changes in plasma free tryptophan and feeding indexes. 128 25

Consistent anorexia was first observed 33 days after inoculating Fischer 344 rats with methylcholanthrene-induced sarcoma. Daily treatment of a similar group of rats with the glutamine synthetase inhibitor, methionine sulfoximine, elicited significant reductions of feeding by day 29 at a dose that had no effect on nontumor-bearing rats. Blood concentrations of ammonia were elevated in both groups of tumor-bearing rats and brain ammonia level was increased in the methionine sulfoximine-treated tumor-bearing rats. Forebrain concentrations of tyrosine, tryptophan, DOPAC and 5-HIAA were elevated in both groups of tumor-bearing rats. Since ammonia is detoxified through the glutamine synthetase reaction, these results suggest that blood and brain ammonia concentrations are more important than the neurochemical consequences of ammonia detoxification for the etiology of cancer anorexia.
 ...
PMID:Methionine sulfoximine intensifies cancer anorexia. 168 54

We reported previously that IL-2 induces tumoricidal activity in IFN-gamma-treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-gamma, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN-gamma plus IL-2 or IFN-gamma plus LPS. IL-4 inhibited IFN-gamma plus IL-2- but not IFN-gamma plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-gamma-induced expression of mRNA for the p55 (alpha) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-gamma plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2R alpha mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-gamma plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression.
 ...
PMID:IL-4 inhibits the costimulatory activity of IL-2 or picolinic acid but not of lipopolysaccharide on IFN-gamma-treated macrophages. 194 Mar 68

FS9 mouse sarcoma cells were previously shown to be highly invasive when confronted with chicken heart fibroblasts using Abercrombie's confronted explant technique. This invasion could be inhibited by addition to the assay of Fab fragments of a monoclonal antibody directed against p37, a protein associated with the surface of FS9 cells. We have cloned and sequenced the gene for p37. We show that it originates from Mycoplasma hyorhinis and that UGA is a tryptophan codon in this organism. We present evidence that the p37 gene is part of an operon encoding two additional proteins which are highly similar to components of the periplasmic binding-protein-dependent transport systems of Gram-negative bacteria, and we suggest that p37 is part of a homologous, high-affinity transport system in M. hyorhinis, a Gram-positive bacterium. We discuss the influence of p37 and M. hyorhinis on contact inhibition of locomotion of mammalian cells.
 ...
PMID:A mycoplasma high-affinity transport system and the in vitro invasiveness of mouse sarcoma cells. 320 56

We have constructed recombinant plasmids capable of expressing in Escherichia coli the intact ras p21 protein encoded by Kirsten murine sarcoma virus. The Ki-ras gene was inserted into an expression vector carrying the E. coli tryptophan promoter and E. coli lipoprotein transcriptional terminator. The resulting plasmids direct the synthesis of large quantities of p21 protein, which represented 20% of the total cellular protein. The Ki-ras p21 protein is immunoprecipitated with monoclonal antibody to p21, and exhibits guanine nucleotide binding activity and autophosphorylation activity. The purified Ki-ras p21 expressed in E. coli has shown to have intact N-terminal and C-terminal amino acid sequences predicted by the nucleotide sequences and migrate as -23K in SDS/polyacrylamide gels.
 ...
PMID:Expression of intact Ki-ras p21 protein in Escherichia coli. 390 44

The association of elevated brain serotonergic activity with cancer anorexia was investigated in three experiments. Significant increases in whole brain tryptophan, serotonin and 5-hydroxyindoleacetic acid in anorectic rats bearing methylcholanthrene sarcomas demonstrated the general nature of this phenomenon. In the Walker 256 sarcoma model, significant increases in whole brain serotonin and 5-hydroxyindoleacetic acid immediately preceded the onset of anorexia, suggesting that these changes in serotonin activity were not caused by decreased food intake. Investigations of regional brain changes in serotonin activity of rats bearing Walker 256 tumors revealed widespread increases in tryptophan, while serotonin was increased in the diencephalon and cerebellum and 5-hydroxyindoleacetic acid was increased in the cortex, hippocampus, diencephalon, pons-medulla and cerebellum. Therefore, these experiments demonstrate that increased brain serotonin activity is a general phenomenon, being observed in two lines of anorexia-producing tumors, that it precedes the onset of anorexia and that selective increases in serotonin activity occur within different regions of the brain.
 ...
PMID:Correlation of changes in brain indoleamine metabolism with onset of anorexia in rats. 617 45


1 2 Next >>