Ehrlich-Ascites tumour

The first step of this sequence, which is not unique to de novo purine nucleotide biosynthesis, is the synthesis of 5-phosphoribosylpyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate. Phosphoribosyl-pyrophosphate synthetase, the enzyme that catalyses this reaction [278], is under feedback control by adenosine triphosphate [279]. Cordycepin interferes with thede novo pathway [229, 280, 281), and cordycepin triphosphate inhibits the synthesis of PRPP in extracts from Ehrlich ascites tumour cells [282]. Formycin [283], probably as the triphosphate, 9-0-D-xylofuranosyladenine [157] triphosphate, and decoyinine (LXXlll) [284-286] (p. 89) also inhibit the synthesis of PRPP in tumour cells, and this is held to be the blockade most important to their cytotoxic action. It has been suggested but not established that tubercidin (triphosphate) may also be an inhibitor of this reaction [193]. 

Although both orotic acid and uracil are utilized by Ehrlich ascites tumour cells in mice [52], the presence of orotic acid completely inhibits the incorporation of bicarbonate into C2 of the acid-soluble nucleotides in the same tumour system [181]. 

Maleuric acid (A -carbamoylmaleamic acid, XVIII), when injected into mice bearing Ehrlich ascites tumours, can produce cytoplasmic abnormalities in all phases of mitosis. This acid also inhibits the incorporation of tritiated thymidine into DNA, and prevents the progression of premitotic cells into mitosis [217]. This substance, which is an open-chain analogue of orotic acid, may possibly be an antimetabolic of this pyrimidine or related compounds. 

Mycelial cultures of Mycena leaiana produce a bright orange pigment, leaianafulvene 117 which exhibits weak antibacterial activities but pronounced cytotoxic activities a 50% lysis of Ehrlich ascitic tumour (EGA) cells was observed at 2.5 pg ml [156]. 

Woerdenbag and coworkers reported on the cytotoxicity of artemisinin endoperoxides to Ehrlich ascites tumour cells . Artemisinin had an IC50 of 29.8 p.M, whereas arteether, artemether, artelininc acid and sodium artesunate all had more potent activities, ranging from 12.2 to 19.9 p.M. It was found that opening of the lactone ring of artemisinin dramatically reduced the cytotoxicity. An ether dimer of dihydroartemisinin 106, prepared by... 

Of compounds I-XI only l-ethyl-3-chloromethylsilatrane (I) has a medium antitumorous effect on Ehrlich ascites tumour, the lifespan of the animals increases by as much as 35—45% (Table 19). 

Kuznicki J, Filipek A, Hunziker PE, Huber S, Heizmann CW. 1989b. Calcium-binding protein from mouse Ehrlich ascites-tumour cells is homologous to human calcyclin. Biochem J 263(3) 951-956. 

The anti-cancer properties of ferrocene-containing molecules first gained attention in the 1970s [12-14] and this field greatly benefited from the discovery of the anti-proliferative properties of simple ferricinium salts on Ehrlich ascite tumours in... 

Parry EW (1981) Cycloheximide treatment modifies the pattern of metastasis following intravenous injection of ehrlich ascites tumour cells. Gann 72 464—467. 

Detailed studies of the kinetics of cholesterol formation from MVA in man have been made and it has been discovered that sub-lines of Ehrlich ascites tumours that did not produce glycogen had a very low rate of steroidogenesis. 

AflBnity Labellii. —Of a large number of 5-substituted-2 -deoxyuridine 5 -mono-phosphates prepared as potential inhibitors of thymidylate kinase, 5-formyl-dUMP was found to be a potent non-competitive inhibitor of the enzyme from calf thymus, and 5-azidomethyl-dUMP irreversibly inactivated both this enzyme and the enzyme from Ehrlich ascites tumour cells. Protection by cofactor addition could only be demonstrated for the latter case, however. 5-Iodoacetamidomethyl-dUMP (68) irreversibly inactivates the tumour enzyme more rapidly than the calf thymus enzyme, and protection could also be demonstrated in this case it has therefore been claimed that (68) is isozyme-specific for the tumour enzyme. ... 

Extracts of various Sophora species have earlier been reported to show antitumour activity, and it was therefore of interest to determine which, if any, of the alkaloidal constituents was responsible for this activity. Kojima et al.21 have now shown that matrine exhibits anti-tumour activity against Ehrlich ascites tumour in mice, and both matrine and matrine N-oxide show activity against solid Sarcoma-180 in mice. In fact, the chemotherapeutic index of matrine IV-oxide for Sarcoma-180 is estimated to be about 7.8 times that of mitomycin C. 

The above described rationale of SAR can be exemplified by the bioactivities of the bromotyrosine derivatives, aeroplysinin-1 and dienone, as well as their complicated molecular substrates aerophobin-1 and isofistularin-3, isolated from the Mediterranean sponge, Aplysina aerophoba. Aeroplysinin-1 and dienone exhibit pronounced biological activity whereas aerophobin-1 and isofistularin-3 were always inactive when tested in equimolar concentrations [23]. Aeroplysinin-1 and dienone are antibiotically active against a broad spectrum of marine bacteria such as Vibrio, Micrococcus, and Alteromonas species [24] and are also cytotoxic to Ehrlich ascites tumour cells and HeLa tumour cells in the microculture tetrazolium (MTT) and clonogenic assays [25]. In these assays, it has been demonstrated that the free radical transformation of aeroplysinin-1 and dienone to its semiquinone structures are responsible for the cytotoxicity [25], Aeroplysinin-1 and dienone are the pharmacophores of aerophobin-1 and isofistularin-3. 

Heparin causes a reduction in mitotic index and a decrease in tumour volume for Ehrlich ascites tumours in mice . Polyethylene sulphonates having molecular weights between 15,000 and 35,000, also have antineo-plastic activity in mice against ascites tumours, carcinomas and leukaemias . Heparin has been found to reduce markedly the number of pulmonary metastases in rats receiving intravenous Walker 256 carcinoma cells . Evans blue in the presence of a sulphated pectin entered tumour cells but not normal tissue cells s. The anti-immunochemical action of heparin has been used successfully for tumour heterografts Ass. 

Lewis lung carcinomas) Effective against Ehrlich ascites tumour, a non viral transplantable (307-309)... 

Moderately active against Ehrlich ascites tumour cells (231)... 

Besides yeast and muscle, glycolytic oscillations have also been observed in Ehrlich ascites tumour cells (Ibsen Schiller, 1967) an insect, the blowfly Phormia terraenovae, for which age-dependent changes in the oscillations have been described (Collatz Horning, 1990 Horning Collatz, 1990) pancreatic p-cells (Chou et al., 1992) and, very recently, heart cells (O Rourke et al., 1994). 

M12. Murray, A. W., Purine phosphoribosyltransferase activities in rat and mouse tissues and in Ehrlich ascites-tumour celk. Biochem. J. 100, 664 (1966). 

Lactate dehydrogenase Cytoplasmic malate dehydrogenase Mitochondrial malate dehydrogenase Ehrlich ascites tumour cells... 

Human fibroblast and leukocyte interferons show a strong affinity for the copper chelate of bis-carboxymethylaminoagarose. Human leukocyte interferon adsorbs non-specifically to immobilized hyperimmune serum immunoglobulin The interferon can be recovered by washing the adsorbent with 1,2-dihydroxyethane. An improved procedure for the isolation of interferons produced by mouse Ehrlich ascites tumour cells infected with Newcastle disease virus provides interferons of three size classes (mol. wts. 3.3 X lO", 2.6x10, ... 

The Na -glucose symporter has been studied most intensively in intestine, but similar translocation catalysts appear to occur in a number of other tissues, for example, in kidney in diaphragm in leucocytes and possibly in Ehrlich ascites tumour cells . 

Carbamoyl phosphate synthesis from ammonia represents one of the prominent activities in ureotelic livers [78]. The enzyme requires N-acetylglutamate and is distinct from the enzyme responsible for carbamoyl phosphate synthesis in extrahepatic tissues and in the livers of uricotelic animals. This second enzyme utilizes glutamine [79], rather than ammonia as the primary nitrogen donor and is found in mushrooms, Escherichia coli, yeast, Ehrlich ascites tumour and several other animal tissues [80]. This enzyme is carbamoyl phosphate synthetase II (ATP carbamate phosphotransferase, EC 2.7.2.2) and catalyses the following reaction ... 

Inhibitor of Purine metab. in Ehrlich ascites tumour cells in vitro. 

Daily intraperitoneal administration of pantothenic acid (100 mg/kg) for 5 days conferred significant protection against the peroxidative actions of a 0.5 ml/kg intraperitoneal dose of CCh in rats (Nagiel-Ostaszewski and Lau-Cam 1990). lipid peroxidation by incubation of Ehrlich ascites tumour cells with FeClj -i- HjOj was partly prevented by preincubation with D-pantothenate, 4 -phospho-pantothenate, D-pantothenol, or pantethine (Sly-SHENOv et al. 1995). Rats exposed to y radiation from a Co source, receiving 0.25 Gy at weekly intervals were protected from the deleterious effects by 26 mg pantothenol/kg x day given for 2 d before each irradiation (Slyshenov et al. 1998). 

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