Effects of cortisone acetate on the lysosomal system of Yoshida ascites sarcoma cells studied by a 1,000 KV electron microscope.
Explore the source record for details and available documents.
Autophagy↗
SEARCH · PubMed Health
Results for “Sarcoma, Yoshida”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis(tetrahydro-2-furanyl)-2,4-pyrimidinedione by oral administration to animals.
The metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FD-1) were investigated in animals, compared with 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FT). It was found that after oral administration of FD-1, the level of 5-fluorouracil (5-FU) was maintained higher and longer than after administration of FT, and that a large amount of 5-FU was released from FD-1 by liver microsomal drug-metabolizing enzymes or spontaneous hydrolysis via 5-fluoro-3-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (3-FT) and FT. FD-1 had a significant activity against the solid form of Ehrlich carcinoma, sarcoma-180, hepatoma AH130, Yoshida sarcoma, Walker carcinosarcoma-256, and leukemia L1210 and P388, but not the ascitic forms, and it produced greater inhibition of tumor growth than FT. The acute toxicity of FD-1 was less than that of FT.
Administration, Oral↗
Antitumor effect of 2-thio-4-hydrazinouracil on transplantable tumors.
The cytostatic activity of 2-thio-4-hydrazinouracil (THU) on some transplantable tumors has been studied. A strong effect of this compound (between 60% and 100% suppression) has been found in the case of Myeloma P-8 (MOPC-21) and Sarcoma 180 (Crocker). A less pronounced effect has been observed on Yoshida sarcoma, while the development of Jensen sarcoma is not influenced.
Animals↗
Effect of 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea on experimental tumors.
The antitumor activity of 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077), a novel water-soluble nitrosourea derivative, against leukemia L1210, Ehrlich carcinoma, sarcoma 180, Lewis lung carcinoma, Yoshida sarcoma, rat ascites hepatomas and Walker 256 carcinosarcoma was examined and compared with those of 3 reference nitrosourea antitumor agents, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. TA-077 exhibited a broad antitumor spectrum against the above tumors. Among these 4 nitrosoureas, TA-077 produced the best therapeutic ratios (OD/ILS30) against leukemia L1210, irrespective of the administration route and schedule employed. The ratio obtained by consecutive treatment (ip) was superior to that by single administration, a unique characteristic of this novel nitrosourea agent. The inhibitory effect of TA-077 on the growth of non-syngenic tumors (solid form) was also significant in all administration routes employed (ip, iv and po). Furthermore, TA-077 showed a marked life-prolonging effect on both early and advanced forms of Lewis lung carcinoma.
Animals↗
Antitumor activity of selected amino acid derivatives against various tumor systems.
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.
Amino Acids↗
Erythrocytes from Yoshida ascites sarcoma-bearing rats have reduced surface charge: the effect of tumor products.
Erythrocytes from the circulation of rats bearing intraperitoneal Yoshida ascites sarcoma, as well as the red cells contaminating the tumor fluid, exhibit higher concanavalin A (Con A)-mediated agglutination than the cells from normal animals. Two proteins have been purified earlier from the ascites fluid that can impart high agglutinability on the cells in vitro. We report here that the erythrocytes from the tumor-bearing rats exhibit reduced electrophoretic mobility compared to the cells from normal animals (P < 0.001), which correlates with the increase in their Con A-agglutinability (r = 0.998). The two purified proteins also cause reduction in the electrophoretic mobility of erythrocytes (P < 0.01). Thus the modification of the host cell surface observed in tumor-bearing rats arises due to non-specific binding of tumor products that reduce the host cell surface charge.
Animals↗
Synthesis and preliminary antitumor evaluation of 4-(SR)-sulfido-cyclophosphamides.
Crystalline 4-(SR)-sulfidocyclophosphamides, sulfido derivatives of activated cyclophosphamide (4-hydroxycyclophosphamide), were synthesized by ozonation of cyclophosphamide and reaction of the intermediate 4-hydroxycyclophosphamide with various thiols (HSR). The products were characterized by elemental analysis, 1H NMR and IR spectroscopy, and mass spectrometry. 1H NMR and polarimetric analysis demonstrated that they consist of racemic cis-isomers that are stable in the crystalline state at room temperature. In aqueous solution these derivatives are hydrolyzed to 4-hydroxycyclophosphamide and the corresponding thiol, with half-lives ranging between 4 and 17 min at 37 degrees C and pH 7. The cytotoxicity of 4-(S-ethyl)- and 4-(S-ethanol)-sulfidocyclophosphamide against Yoshida sarcoma ascites cells and the toxicity in rats were found to be practically identical with those of activated cyclophosphamide. A preliminary evaluation of the curative effect after a single IV injection of 4-(S-ethane)- and 4-(S-ethanol)-sulfidocyclophosphamide in rats bearing Yoshida ascites sarcoma or of 4-(S-ethanol)-sulfidocyclophosphamide in nu/nu mice bearing human breast carcinoma xenografts suggested that these sulfido derivatives possess the same oncostatic efficacy as activated cyclophosphamide itself.
Animals↗
[Synthesis and antitumor action of N,N-di(2-chlorethyl)-hydrazines of alpha-aminocarboxylic acid antimetabolites].
The N,N-di(2-chlorethyl)hydrazides of the following alpha-aminocarboxylic acid antimetabolites: methioninsulphoxide, ethionine, 2-, 3- and 4-fluorophenylalanine, 4-nitrophenylalanine and 2,2-dimethyl-thiazolidine-4-carboxylic acid were synthesized. Preliminary studies of the activity on experimental tumour models were carried out. It was shown that these compounds have a high antitumour effect (80-100%) on sarcoma Yoshida and carcinosarcoma Walker.
Amino Acids↗
Selective delivery of 10B to soft tissue sarcoma using 10B-L-borophenylalanine for boron neutron capture therapy.
Boron neutron capture therapy (BNCT) may improve the locoregional control of radio/chemoresistant tumours like soft tissues sarcomas (STS). This technique uses the 10B(n,alpha)7Li nuclear reaction to destroy tumour cells, provided that a sufficient amount of 10B may be carried selectively into them. In order to evaluate the targeting potential of 10B-L-borophenylalanine (BPA) a 10B biodistribution study was carried out in 24 Wistar rats bearing Yoshida sarcoma. Six animals received increasing intraperitoneal doses of BPA (300, 600 and 1200 mg kg-1), while the remainder received a BPA dose of 600 mg kg-1 but with a sacrifice at six different time points: 1, 2, 4, 6, 9 and 12 h. The 10B concentrations in the tumours, normal tissues and blood were analysed with neutron capture radiography (NCR). The analysis shows that 36 micrograms g-1 (+/- 4 SD) of 10B may be incorporated into the tumour, with a ratio of 13 (+/- 4 SD) versus the muscle and a ratio of 15 (+/- 3 SD) versus the blood, 6 h after an intraperitoneal injection of 600 mg kg-1 of BPA. The BPA appears to be abundantly incorporated in the tumour, and the kidney proximal tubule area. These data suggest that BNCT using BPA may provide an improved therapeutic ratio for the treatment of STS.
Animals↗
Antibacterial and antitumor activity of some derivatives of ureidosuccinic acid.
The effect of several derivatives of ureidosuccinic acid on the growth of Escherichia coli 387, Staphylococcus aureus strain 209 and its mutant UV-2, Sarcina lutea, Candida tropicalis and Neurospora crossa 9863 as pre-screening systems for antitumor activity was studied. It was found that dihydrazide of D,L-ureidosuccinic acid (DHUA) had a marked antibacterial activity. The inhibitory effect of DHUA on N. crassa could not be removed by aspartic acid, ureidosuccinic acid, dihydroorotic acid, orotic acid, uracil or cytosine. DHUA suppressed the growth of Myeloma P-8 by 38%, that of Sarcoma 180 by 12% and that of Yoshida sarcoma by 19%. No effect was found on the growth of Lymphosarcoma Pliss.
Antineoplastic Agents↗
The effects of bifunctional alkylating agents on DNA synthesis in sensitive and resistant Yoshida cells.
The effects of the alkylating agents methylene dimethanesulphonate (MDMS), sulphur mustard (SM) and methyl methanesulphonate (MMS) on DNA synthesis have been investigated in Yoshida sarcoma cell lines sensitive (YS) and resistant (YR) to these agents. Measurement of overall DNA synthesis by [3H]thymidine uptake into DNA indicated that both MDMS and SM, but not MMS, induced a greater depression of DNA synthesis in YS cells than in YR cells. Analysis of the sizes of newly synthesised strands of DNA by pulse labelling and alkaline sucrose gradient sedimentation revealed that MDMS inhibited the initation of new replicons and also reduced the size of new DNA strands. The relative extents of inhibition of replicon initation in MDMS-treated YS and YR cells were similar and reduced by caffeine while YR cells were comparatively less sensitive to the effect of MDMS on the sizes of DNA molecules synthesised. Similarly, YR cells apparently synthesised longer DNA strands following SM treatment compared to YS cells suggesting an association between the size of DNA molecules synthesized and the sensitivity of Yoshida cells to bifunctional alkylating agents.
Alkylating Agents↗
Characteristics of dimer formation, excision and DNA strand growth in Yoshida sensitive and resistant cells after ultraviolet irradiation.
The sedimentation properties of the nascent DNA of Yoshida sarcoma cells, sensitive and resistant to methylene dimethane sulphonate and cross-resistant to U.V. light, have been studied after irradiation with U.V. light at 11 and 22J/m2. It has been shown that the DNA formed immediately after irradiation with 11J/m2 is some eight to nine times longer than the calculated inter--dimer distance in both cell-lines. Differences were, however, observed between the two cell-lines, in that the absence of excision of dimers in the sensitive cells was accompanied by the formation of a DNA component of low molecular weight, whereas excision in the resistant line was not so accompanied. There are some similarities between the Yoshida tumour line sensitive to methylene dimethane sulphonate and the U.V.-sensitive line of Xeroderma pigmentosum.
Animals↗
Glutamine and arginine metabolism in tumor-bearing rats receiving total parenteral nutrition.
Arginine supplementation increases glutamine levels in muscle and plasma. Since glutamine production is increased in catabolic states, these observations prompted us to investigate whether the flux of arginine to glutamine was increased in tumor-bearing (TB) rats, and we measured the synthesis rate of glutamine from arginine in control versus TB rats receiving standard total parenteral nutrition (TPN) solution. Male Donryu rats (N = 36; body weight, 200 to 225 g) were divided into two groups, control and TB rats. Yoshida sarcoma cells (1 x 10(6)) were inoculated into the back of the rats (n = 18) subcutaneously on day 0. The rats were given free access to water and rat chow. On day 5, all animals, including non-TB rats (n = 18), were catheterized at the jugular vein and TPN was begun. On day 10, TPN solution containing either U-14C-glutamine (2.0 microCi/h) or U-14C-arginine (2.0 microCi/h) was infused as a 6-hour constant infusion. At the end of the isotope infusion, plasma was collected to determine the glutamine production rate in rats receiving U-14C-glutamine, and the ratio of specific activity of glutamine to specific activity of arginine was measured in rats receiving U-14C-arginine. Only 2 g tumor caused a decrease in glutamine levels and an increase in glutamine and arginine production. The low flux rate of arginine to glutamine was observed in control rats (Arg to Gln, 41.0 +/- 11.9 mumol/kg/h). On the other hand, TB caused a significant increase in Arg to Gln compared with the control (213.3 +/- 66.1 mumol/kg/h, P < .01 v control). An increase in the flux rate of Arg to Gln was associated with an enhancement in the ratio of specific activity of ornithine to specific activity of arginine in TB rats (control 51.5% +/- 10.9% v 77.4% +/- 8.9%, P < .05). We conclude that (1) glutamine and arginine metabolism is altered with very small tumors, (2) although the flux of Arg to Gln was increased in TB and rats, the small increase in Arg to Gln cannot explain the observed large increase in Gln production.
Animals↗
[Agent of Yoshida type ascites-sarcoma].
Explore the source record for details and available documents.
Animals↗
[On the problem of a selective thermosensitization of carcinoma cells in vivo with vitamin K3-sodium bisulfite, methylene blue and other thermosensitizers. 2. Studies of an effect of hyperthermia and in-vitro-thermosensitizers on the Yoshida- and Jensen-sarcoma of rat].
Explore the source record for details and available documents.
Animals↗
Antitumor activity of BOF-A2, a new 5-fluorouracil derivative.
A compound containing both CNDP (3-cyano-2,6-dihydroxypyridine), an inhibitor of 5-fluorouracil (5-FU) degradation, and EM-FU (1-ethoxymethyl-5-fluorouracil), a masked form of 5-FU, was synthesized and named BOF-A2 (3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1-ethoxy methyl-5- fluorouracil). The antitumor activity of BOF-A2 was investigated in sarcoma-180-bearing mice and Yoshida sarcoma-bearing rats. The ED50 (the dose for 50% inhibition) values of BOF-A2 were 25 mg/kg against sarcoma-180 and 15 mg/kg against Yoshida sarcoma. In vitro studies showed that BOF-A2 was rapidly degraded to EM-FU and CNDP in homogenates of the liver and small intestine of mice and rats, and in sera of mice, rats and human, and the conversion of EM-FU to 5-FU occurred only in the microsomal fraction of rat liver in the presence of NADPH. After oral administration of BOF-A2 at 15 mg/kg to Yoshida sarcoma-bearing rats, BOF-A2 was hydrolyzed to EM-FU, CNDP and 5-FU, and their maximum concentrations in the blood were 2000 ng/ml, 300 ng/ml and 40 ng/ml, respectively. Moreover when BOF-A2 was given at the same dose to tumor-bearing mice and rats, the 5-FU levels in the tumor tissue increased much more than those in the blood and persisted for more than 8 h, whereas those in the blood decreased more rapidly. This accumulation and maintenance of a high level of 5-FU in the tumor tissue are concluded to be related to the high antitumor activity of BOF-A2.
Administration, Oral↗
Hypoxyradiotherapy: lack of experimental evidence for a preferential radioprotective effect on normal versus tumor tissue as shown by direct oxygenation measurements in experimental sarcomas.
AIM: In order to investigate possible pathophysiological mechanisms underlying the postulated preferential protective effect of hypoxia on normal tissue during radiotherapy, the impact of acute respiratory hypoxia (8.2% O2 + 91.8% N2) on tissue oxygenation was assessed. METHODS: Tumor and normal tissue oxygenation was directly determined using O2-sensitive electrodes in two experimental rat tumors (DS and Yoshida sarcomas) and in the normal subcutis of the hind foot dorsum. RESULTS: During respiratory hypoxia, arterial blood O2 tension (pO2), oxyhemoglobin saturation and mean arterial blood pressure decreased. Changes in the arterial blood gas status were accompanied by a reflex hyperventilation leading to hypocapnia and respiratory alkalosis. In the subcutis, tissue oxygenation worsened during acute hypoxia, with decreases in the mean and median pO2. Significant increases in the hypoxic fractions were, however, not seen. In tumor tissues, oxygenation also worsened upon hypoxic hypoxia with significant decreases in the mean and median pO2 and increases in the size of the hypoxic fractions for both sarcomas. CONCLUSION: These results suggest that during respiratory hypoxia, radiobiologically relevant reductions in the oxygenation (and a subsequent selective radioprotection) of normal tissue may not be achieved. In addition, in the tumor models studied, a worsening of tumor oxygenation was seen which could result in an increased radioresistance.
Animals↗
Chemical and biological properties of 2-pyridyl-benzyl-carbinol.
Three isomers of pyridylbenzylcarbinol were synthetized and their chemical properties and biological activity were studied. Clear dependence between chemical structure and antitumor activity was observed. As expected most active appeared 2-pyridylbenzylcarbinol (alpha-carbinol). It showed significant antitumor activity against subcutaneous tumors of Ehrlich carcinoma. Nemeth-Kellner lymphoma and sarcoma 180. On a chronic treatment schedule tumor inhibition from 60 to 80% was induced. No activity was seen in L1210 and P388 models. In B16 melanoma the significant inhibition of tumor growth was obtained at 200 mg/kg/injection. Tumor inhibitory effect was also observed in Yoshida sarcoma. Depending on a dose and schedule the increase in lifespan from 45 to 147% was achieved. LD50 and MTD were determined and were 750 +/- 87.65 mg/kg and 557.8 mg/kg, respectively. Only slight suppressive effect of alpha-carbinol on immunological system was showed. It concerned mainly immunological reactions with cellular system involved, in which distinct suppressive effects were noted. Specific and nonspecific humoral reactivity was little or not at all affected by alpha-carbinol.
Animals↗