Ehrlich tumours

Rutman, R. J., Chun, E. H. L., and Lewis, F. S. (1968) Permeability difference as a source of resistance to alkylating agents in Ehrlich tumour cells. Biochem. Biophys. Res. Commun. 32, 650-657. 

V2. Van den Brenk, H. A. S., Elliot, K., and Hutchings, H., Effect of single fractionated doses of x-rays on radiocurability of solid Ehrlich tumour and tissue reactions in vivo, for different oxygen tensions. Brit. J. Cancer 16, 518-534 (1962). 

Ehrlich tumours are poorly differentiated malignant tumours (originally a breast carcinoma in a mouse), which grow in solid and ascetic forms. HeLa cells are a cell line developed from cervical cancer of a woman ( enriette Lacks), who died from that cancer in 1951. 

Leuthauser also observed that solid Ehrlich tumours taken from mice treated with Cu(IIX3,5-DIPS)2 contained differentiated epithelial cells in duct arrangement, suggesting that Cu(IIX3,5-DIPS)2 treatment did not kill these tumour cells but caused them to differentiate to normal duct cells [380]. This observation was confirmed and extended by Sahu in his dissertation [381]. He... 

Methylisocytosine (LVIII, superacyl) has been reported to stimulate antibody production in rabbits to an extent greater than with a vaccine alone [354]. It also markedly reduced the development of pulmonary adenoma at 100 mg/kg per day for 10, 25 or 50 days s.c. or p.o. to mice, following a single i.p. injection of urethan. 5-Hydroxy-6-methylisocytosine had the same effect [19]. In tests on the effect of pyrimidines on reticuloendothelial functions in mice, the absorptive capacity of this system increased with 5-(hydroxymethyl)uracil or with 6-methylisocytosine. The effect was most pronounced when superimposed on cortisone inhibition [355]. When administered subcutaneously to mice, 6-methylisocytosine increased the inhibitory effect of thio-TEPA on the growth of Ehrlich tumours in mice. It is believed that this pyrimidine prevents the development of metastases [356]. 

Conversion of 4-aminopyrazolo [3,4-d] pyrimidine (VIII) to its ribonucleotide by mouse tumours and host tissues has been observed [118,119]. Although no evidence of the anabolism of A -methyladenine (111) [120] to the ribonucleotide was obtained in mice with Ehrlich ascites carcinoma [121, 122], it is anabolized by bacteria [123. 124] and the enzyme responsible was partially purified from Salmonella typhimurium [125]. Human epidermoid carcinoma No. 2 cells resistant to 2-fluoroadenine (H.Ep.-2/FA) have lost adenine phosphoribosyl-... 

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. 

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

Quantitative evaluation of 5-diazouracil against Walker 256 carcinosarcoma, Ehrlich ascites carcinoma, C3H-FX lymphoma and other tumour systems has been studied and detailed results in comparison with other standard active agents have been reported [332]. 

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... 

Furthermore, mouse model against Ehrlich s ascites tumour (EAT) [36]. This study showed that the treatment with ama-titano-cene 48 increases the lifespan of EAT-bearing mice from 25% to around 50% in a dose-dependent manner, and myelopoiesis (the formation of bone marrow or of blood cells derived from bone marrow) was not suppressed. Additionally, these experiments showed that ansa-titanocene 48 restores the natural killer cell function, which is reduced due to a dysfunction in EAT, and stimulates the natural killer cell-mediated cytotoxicity. 

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. 

On the basis of inhibition experiments of ribonucleases from Ehrlich ascites (EA) tumour cells by nucleoside 2 (3 ),5 -bisphosphates, it has been concluded that these... 

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. 

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