Ehrlich Ascites Tumor Growth Research Articles

Antioxidant effects in the development of Ehrlich ascites carcinoma

The effect of Ehrlich ascites tumor growth on selenium-turnover rates and selenium-75 distribution in liver, kidney, and immunological tissues (spleen, thymus, and lymph nodes) was investigated in Swiss Webster mice that had been pre labeled with selenium-75. Ehrlich ascites tumor caused a decrease in the selenium-75 content of liver, kidney, and thymus; it also decreased the rate of the total-body selenium-turnover. In liver, depletion of selenium-75 was almost as great as that produced by a selenium and vitamin E-deficient diet. When mice had been fed an antioxidant-deficient diet, considerable quantities of selenium-75 were accumulated by the tumor; the specific activity of the tumor increased 9-fold over that in antioxidant-supplemented mice. The same diet produced a premature, and in some cases drastic, contraction in tumor volume. The possible significance of tumor-induced antioxidant deficiencies to the etiology of certain paraneoplastic syndromes is discussed.

Ascitic versus solid growth of Ehrlich ascites tumor influenced by immunological factors.

A certain number of CBA mice injected intraperitoneally with 1 X 10(6) or fewer Ehrlich ascites tumor (EAT) cells did not develop ascites tumors but solid tumors at the inoculation site. The incidence of solid tumors proved dependent on the level of immunological reactivity of recipients, being increased in mice with increased immunological potency and absent in mice in which this potency was reduced. Mice bearing solid tumors had increased level of cytotoxic antitumor antibodies in serum. Possible reasons for a greater immune resistance of cells growing in subcutaneous tissue, than in the abdominal cavity, are discussed.

Tumor growth inhibition mediated by trypsin inhibitor or urokinase inhibitors

When testing in vitro, we often observed that erythrocytes taken from Ehrlich ascites tumor bearing mice displayed enhanced agglutinability by the lectin Concanavalin A, suggesting that protease activity operates in vivo. In several studies, we were able to inhibit Ehrlich ascites tumor growth by the repeated administration of soya bean trypsin inhibitor. Studies of dosages and schedules of treatment showed that for 20,000 initially grafted cells, treatment resulted in 0–70% of long-term survivors and induced a significant increase in mean survival time of treated mice over control mice. For 200,000 grafted tumor cells, 0–40% of long-term survivors were recorded. In a comparative study, we found that different inhibitors of urokinase displayed a similar chemotherapeutic effect against 200,000 inoculated cells. Our results corroborate the idea that a plasminogen activator monitored chain of fibrinolytic and proteolytic activity controls tumor growth and metastasis enzymatically.

The influence of ehrlich ascites tumour growth on the turnover of lactate dehydrogenase in tissues of the mouse

1. 1. The influence of Ehrlich ascites tumour growth on the turnover of total soluble protein and lactate dehydrogenase (LDH) in mouse tissues has been studied. 2. 2. Turnover parameters were determined by means of double-labelling technique, with the enzyme (LDH) being isolated by affinity chromatography. 3. 3. Tumour growth was accompanied by a decreased rate of synthesis of total protein in all tissues. 4. 4. Lactate dehydrogenase by contrast snowed an increased rate of synthesis in all tissues but kidney. 5. 5. These directions of change, in combination with the lesser response of degradation constants, resulted in a consequent conservation of enzyme activity in all tissues except kidney. 6. 6. A generalized shift in the LDH isozyme pattern of these tissues was also observed during tumour growth with an increased contribution of A-type subunit. 7. 7. These results have been discussed in relation to the redirection of protein synthesis and degradation, the occurrence of foetal isozymes, and possible mechanisms involved in the redistribution of protein resources in the animal during tumour development.

Effect of Ehrlich ascites tumour on the clinical course and pathology of mice having carbon tetrachloride-induced hepato-renal necrosis.

Ehrlich ascites tumour, administered intraperitoneally 18 hr following a dose of CCl4 by stomach tube, produces and irreversible illness characterised by failure to resolve extensive hepato-renal necrosis. Equally extensive hepato-renal necrosis occurs in animals given CCl4 and saline; such animals, however, remain clinically well and show rapid histological regeneration of both organs. Carbon tetrachloride given to mice on day 5 of tumour growth produces hepatic necrosis only, the kidney of such animals being immune to the necrotising effect of CCl4. Such animals remain well, and histological recovery of the liver is rapid. It is proposed that the Ehrlich tumour produces a "regeneration-inhibiting" toxin, active against the damaged liver and kidney; the CCl4-damaged kidney fails to excrete this toxin, hence the irreversibility of hepato-renal damage and a fatal outcome. A marked reduction of ascites volume as compared with controls was observed in those animals given Ehrlich tumour 18 hr after CCl4, but not in animals given CCl4 on day 5 of Ehrlich ascites tumour growth.

Antineoplastic agents. 1. N-Protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine.

A series of N-protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine was synthesized and these compounds were evaluated for antitumor activity against the growth of Ehrlich ascites carcinoma in CF1 male mice (33 mg/kg/day), Walker 256 carcinosarcoma in Sprague-Dawley male rats (2.5 mg/kg/day), and P388 lymphocytic leukemia in DBA/2 mice (20 mg/kg/day). Structure-activity relationships were evaluated and acute toxicity studies (LD50 determinations) in male CF1 mice were also carried out on selected compounds. Carbobenzoxy-L0phenylalanine vinyl ester (5), N-carbobenzoxy-L-phenylalanine 1,2-dibromoethyl ester (12), and N-carbobenzoxy-L-phenylalanine cyanomethyl ester (8) were found to be very potent inhibitors of Ehrlich ascites tumor growth at nontoxic doses cited above. Compounds 5 and 12 also tripled survival time in the Walker 256 system. LD50 values for compounds 5, 12, and 8 were greater than 2000 mg/kg (greater than 6.15 mmol/kg), 74 mg/kg (0.15 mmol/kg), and 150 mg/kg (0.44 mmol/kg), respectively.

Proteases during the growth of Ehrlich ascites tumor. III. Effect of e-aminocaproic acid (EACA) and heparin

The effect of heparin and e-aminocaproic acid (EACA) on the in vivo growth of Ehrlich ascites tumors was studied. The drugs were administered intraperitoneally every 8 hr for 8 consecutive days beginning 16 hr after transplant of 10 million tumor cells. Heparin doses studied ranged from 50 to 800 units/kg and EACA doses were 125–2000 mg/kg. Criteria for therapeutic effect included measurement of total ascites volume (TAV) and total packed cell volume (TPCV) determined 16 hr after the last drug injection. Both heparin and EACA exerted a dose-dependent chemotherapeutic effect. Heparin, at the highest dose of 800 units/kg significantly reduced TAV by an average of 46.9% (P< 0.01–<0.005) and reduced the TPCV by an average of 46.1% (P< 0.01–<0.005). At the lowest heparin dose of 50 units/kg a biphasic inhibitory response was obtained reflected by a decrease in both TAV ( 26.1%, P< 0.025–<0.01) and TPCV ( 26.3%, P< 0.05–<0.005). EACA, at the highest dose of 2000 mg/kg, inhibited TAV by 56.3% (P < 0.001) and TPCV by 48.1% (P< 0.001).

Effects of naturally occurring sugars on Ehrlich ascites tumor growth in mice.

The growth of Ehrlich ascites tumor cells in Swiss mice was modified by the addition of certain naturally occurring sugars to the drinking water or by ip inoculation of mice after infection. D-Mannose, D-ribose, and D-glucosamine produced the most striking antitumor effects, increasing significantly the survival rate in mice so treated.

Antitumor agents. 16. Steroidal alpha-methylene-gamma-lactones.

Several novel steroidal alpha-methylene-gamma-lactones and related derivatives have been synthesized as potential steroid alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper steroidal ketones. In vitro assay for the cytotoxicity of these compounds against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) has shown significant activity. Cytotoxicity was improved at least sixfold with the introduction of lipophilic steroidal character. Preliminary in vivo tumor assay also indicated that these compounds were active against Walker 256 carcinosarcoma in rats and were inactive against both L1210 lymphoid leukemia and Ehrlich ascites carcinoma in mice. However, the simple alpha-methylene-beta,beta-dicarbethoxy-gamma-butyrolactone significantly inhibited Ehrlich ascites tumor growth.

Variation of cell kinetic parameters in relation to the growth rate of the Ehrlich ascites tumor.

A multicompartmental model of the cell cycle and proliferation kinetics was used to analyse the time-course behavior of the cell cycle time, the growth fraction, and the cell loss rate during Ehrlich ascites tumor growth. The growth rate of Ehrlich ascites tumor cells as the tumor aged was significantly influenced by change in the cell cycle time.

RECALL OF TUMOUR RESISTANCE IN LONG‐TERM SALMONELLA ENTERITIDIS 11RX IMMUNISED MICE

SummaryResistance to Ehrlich ascites tumour growth in the peritoneal cavity of mice has been induced by prior immunisation with live Salmonella enteritidis 11RX. A greater and longer lasting anti‐tumour effect was elicited after immunisation by the intraperitoneal (i.p.) route than by the intravenous (i.v.) route. Resistance to tumour could be recalled after either i.p. or i.v. immunisation by i.p. injection of various 11RX antigen preparations, including a preparation which was not protective in normal mice. Resistance was determined by following survival of mice after challenge with tumour cells and by monitoring the death of 131I‐iododeoxyuridine‐labelled tumour cells in vivo. Recall of tumour resistance was attributed to the rapid induction of an in vivo tumour killing mechanism.

Effect of some acyl derivatives of amino acids on cell-free protein synthesizing systems from Ehrlich ascites, rat and mouse liver cells

Intraperitoneal injections of carbobenzoxy (CBZ)phenylacetyl and phenylpropionyl derivatives of ammo acids, especially derivatives with more than one aromatic group, were found to markedly inhibit the growth of Ehrlich ascites tumor in mice [l-3] .I Such derivatives also strongly inhibit a number of isolated enzyme systems (rat liver asparaginase and glutaminase [4,5] , rat liver and ovine brain glutamine synthetase [6,7] , rat liver NAD-synthetase [8] and the purine synthesizing system of pigeon and chicken liver [9]. Preliminary experiments with suspensions of Ehrlich ascites cells carried out in this department by G. Mor also revealed that ol,e-di-CBZL-lysine and N-CBZ-S-benzyl-L-cysteine markedly inhibit the incorporation of L-leucine and L-phenylalanine into ascites protein. The latter finding, however, does not necessarily indicate that these compounds inhibit the protein synthesis as such (e.g., they might affect some ATP generating enzyme systems). We decided therefore to investigate the effect of the above amino acid derivatives on cell-free protein synthesizing systems prepared from Ehrlich ascites cells and from rat and mouse liver. The present paper deals with this subject.

癌の増殖に関する研究

The author's previous paper reported that chondroitin sulfate and some other substances accelerated the growth of Ehrlich ascites tumor. In this paper. the author studied the relationship between inflammation and tumor growth.The tumor cells were transplanted to the back of mice where inflammation had been proboked by injecting croton oil two days prior to the transplantation.Experiment 1.The daily growth of the transplanted Ehrlich ascites tumor was observed in the controls and the groups with either chondroitin sulfate or the inflammation until the 14th day after the transplantation when they were killed.The tumor growth in both the chondroitin sulfate group and the inflammation groups was significantly faster than in the control group (P<0.01).Experiment 2.Using sarcoma 180, the same experiment was performed and the same results were obtained as in the Ehrlich ascites tumor.Experiment 3.The influence of chondroitin sulfate and the inflammation on the growth of Ehrlich ascites tumor was histologically studied.1. Although no morphological differences of the tumor cells themselves were found in the group pretreated with chondroitin sulfate as compared with the control, the space between each tumor cell was wide, and tumor tissue seemed to have grown multifocally. The number of ma-The number of mast cells around the tumor tissue was definitely increased in the chondroitin sulfate group, but there was not so much difference in the amount of connective tissue and metachromatically stained fibers.2. Compared with the control group, the inflammation group showed large amount of connective tissue around the tumor, and the tumor cells seemed to have been scattered into the network of fibrous tissue.The number of mast cells was decreased in the inflammation group.These findings were not observed in the chondroitin sulfate group.

Pharmacological Evaluation of Medicinal Plants From Western Samoa

A total of 110 plant parts from 34 different species of medicinal and toxic plants was collected for pharmacological testing in or near the Lefaga District on the island of Upolu in Western Samoa. Voucher specimens of all species were also made. From the 110 plant parts, 211 different extracts were prepared and evaluated for antiviral, antibacterial, and anti-Ehrlich ascites tumor properties and for effects on blood pressure, heart rate, respiration, electrocardiogram, electroencephalogram, and gastric motility. Twelve extracts were effective in vitro as antibacterial agents and six inhibited Ehrlich ascites tumor growth in mice. Ninety-one extracts showed hypotensive properties, 31 for more than 30min.

Effect of sialic acid, kerato sulfate and neuraminidase on the growth of solid Ehrlich ascites tumor

The effect of sialic acid, keratosulfate and neuraminidase on the growth of solid Ehrlich ascites tumor has been investigated. Various concentrations of test materials were given subcutaneously into the back of ddN mice, followed by tumor inoculation. On the 8 th day after tumor inoculation, average tumor weights in experimental groups were compated with those in controlgroups, which were given isotonic saline. 2% keratosulfate and 0.2% sialic acid accelerated the growth of tumors to some extent, while 2% sialic acid had a tendency to inhibit it. Neuraminidase solution tested so far had no significant effect on the tumor growth.

Effect of chondroitinases on the growth of solid Ehrlich ascites tumour.

The effect of various glycosidases on the growth of solid hypotetraploid Ehrlich ascites tumour was investigated. The purified bacterial chondroitinase-ABC significantly inhibited the growth of tumour; chondroitinase-AC inhibited the tumour to some extent but chondro-4-sulphatase, chondro-6-sulphatase, streptomyces hyaluronidase, and β-glucuronidase had no inhibitory effect. Heat-treated chondroitinase-ABC had no inhibitory effect on the tumour growth. The growth of tumour cells which were injected subcutaneously after in vitro incubation with chondroitinase-ABC or -AC solution was decreased when compared with that of sham-treated cells.The injection of 1 ml of chondroitin sulphate A and chondroitin sulphate C solution prior to tumour inoculation into the same site promoted the tumour growth, while growth-stimulating effect of chondroitin sulphate B was ambiguous. The chondroitin sulphate appears to serve as a growth supporter which protects the surface of tumour cells and promotes the physiological surface function of the cells.

Effect of urease injections on Ehrlich ascites tumor growth in mice.

SummaryMature male Swiss Webster mice bearing solid and ascitic forms of Ehrlich ascites tumor (EAT) were injected with 0.1 to 0.4 unit of crystalline jack bean urease per injection. Mice given 12 × 106 EAT cells sc and injected with 0.4 unit of enzyme at 12 and 24 hr thereafter had tumors at 3 weeks which weighed 40% of those in mice given 0.85% NaCl instead of urease. Liver, spleen, and brain weight changed significantly in mice bearing solid EAT and this change was reduced significantly in urease-treated animals. Animals given 0.4 unit of urease as described above showed a significant reduction in body weight compared to non-urease-treated animals. Mice bearing ascitic EAT injected with 0.2 unit of urease on days 6 and 7 after EAT inoculation and killed 5 days thereafter showed significant elevations of ascitic fluid ammonia and cell to ascitic fluid volume ratio, The latter urease-treated animals showed a significant decrease in body weight at 24 and 48 hr after the second urease injection. The half-t...

Experimental study on interaction between the growth of malignant tumor and connective tissue with special references to acid mucopolysaccharides.

In order to study the interaction between connective tissue and cancer cells, the effect of acid mucopolysaccharides on the subcutaneous growth of Ehrlich ascites tumor was investigated.Chondroitin sulfate was injected subcutaneously into the back of mice, followed immediately by tumor inoculation into the same site. Average tumor weights in chondroitin sulfate‐treated groups were greater than that in control groups, showing statistically significant difference. By means of the same procedure, the effect of chondroitin sulfate and its components on the tumor growth was surveyed quantitatively with various amounts and concentrations, and its activity under the influences of other interstitial components, hydrocortisone and rechallenge was also observed.Results from this experiment indicated that chondroitin sulfate promoted the tumor growth and appear to show that the proliferation of new connective tissue which produces acid mucopolysaccharides is favorable to the growth of cancer cells. Interaction between connective tissue and tumor growth was discussed from a view‐point of intercellular components.

Effect of withaferin A on Ehrlich ascites tumor cells--cytological observations.

AbstractWithaferin A, a steroidal lactone with carcinostatic properties, isolated from the leaves of Withania somnifera Dun., produced a mitotic arrest in the metaphase of dividing Ehrlich ascites carcinoma cells. In addition this compound also induced vacuolization of the cytoplasm. A single dose of withaferin A, administered 24 hours after Ehrlich ascites implantation, caused growth reduction followed by disappearance of the tumor in 80% of the mice. These mice were found to be resistant to rechallenge with Ehrlich ascites tumor cells. The inhibition of Ehrlich ascites tumor growth is thought to represent a combined effect of withaferin A action and immune reactions.

Kinetics of Ehrlich ascites tumor growth within millipore chambers in normal and immunized mice.

Kinetics of Ehrlich ascites tumor growth within millipore chambers in normal and immunized mice