Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of tumor cells implanted into the brain of animals on survival rates and gross and microscopic brain changes have been ascertained. Walker carcinosarcoma 256 cell suspensions were injected at several brain sites in rats and leukemia L1210 and P388 and Ehrlich ascites tumor cells, intracerebrally into BDF1 mice. Such neoplasms provided for rapid and rather predictable growth increments. The survival rates were dependent on the number of cells introduced, those receiving the higher counts succumbing first. The brains of the animals revealed fairly discrete space-occupying lesions and neurological symptoms became apparent only hours before death due to intracranial pressure.
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PMID:Brain changes and survival of animals with tumors implanted in the brain. 116 Dec 58

Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.
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PMID:Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds. 160 Dec 18

Several procedures which have been reported as effective for the control of cisplatin induced nephrotoxicity were compared in the Sprague-Dawley rat using the same dose of cisplatin. The treatments examined were based on the use of sodium thiosulfate, sodium diethyldithiocarbamate (DDTC), glutathione (GSH), sodium N-methyl-D-glucamine dithiocarbamate (NaG) and S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). The differences in the effectiveness of the procedures were assessed using BUN and serum creatinine values, histopathological examination, body weight changes, and renal platinum levels as indices. The effect of such treatments on the antineoplastic activity of cisplatin were examined with both the Walker 256 carcinosarcoma in the rat and the L1210 murine leukemia in mice. Under the conditions used, GSH was found to be more effective than the other nucleophiles in protecting against the nephrotoxicity of cisplatin while providing the least amount of interference with the antitumor activity as measured against the Walker 256 carcinosarcoma and the L1210 murine leukemia. Simultaneous i.v. administration of cisplatin and any of the sulfur-containing nucleophiles leads to a significant protection against the nephrotoxicity but reduced the anti-neoplastic activity of cisplatin when measured against the Walker 256 carcinosarcoma.
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PMID:Relative effectiveness of some compounds for the control of cisplatin-induced nephrotoxicity. 189 97

A novel antitumor compound, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea (HO-221) was evaluated for its antitumor activity in experimental tumor models. HO-221 preparation was given orally to tumor-bearing animals. The compound exhibited significant effects against various tumors such as P388 and L1210 leukemias; M5076 reticulum-cell sarcoma; colon 38 carcinoma; human xenografts MX-1, LX-1, GA-1, and Co-1; Lewis lung carcinoma; sarcoma 180; and Walker 256 carcinosarcoma and was especially effective against solid tumors. However, its effect on murine B16 melanoma was moderate. Intermittent administration of HO-221 produced better results. The effects of HO-221 on human tumor xenografts were compared with those of other antitumor agents. HO-221 showed activity against LX-1 lung and Co-1 gastrointestinal tumor and was also effective against advanced-stage L1210 leukemia and Lewis lung carcinoma. Furthermore, the effect of HO-221 on drug-resistant tumors was examined using murine leukemias L1210 and P388. It showed no cross-resistance with the known antitumor agents Adriamycin (ADM), daunomycin (DM), vincristine (VCR), mitomycin C (MMC), cisplatin (CDDP), 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C), methotrexate (MTX), cyclophosphamide (CPA), or carboquone (CQ), and collateral sensitivity to HO-221 was found in MMC-, CDDP-, and CPA-resistant sublines. HO-221 exhibits significant reproducible, broad-spectrum antitumor activity against experimental tumors as well as human neoplasms.
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PMID:Antitumor activity on murine tumors of a novel antitumor benzoylphenylurea derivative, HO-221. 191 78

The ability of a variety of analogues of tamoxifen to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined. Effective inhibition requires that the aminoethoxy side chain bears a positive charge at physiological pH and is not too bulky. Amongst 4-substituents, inhibitory potency increases with lipophilicity. The stereochemistry about the olefinic linkage is not important. The most potent agent found (IC50 1.4 microM, compare tamoxifen = 6.75 microM) has a 4-iodine substituent and pyrrolidino in place of dimethylamino. This analogue is also more cytotoxic than tamoxifen against MCF-7 human breast cancer cells as determined in a 24-hr assay, but there was no correlation found between calmodulin inhibition and cytotoxicity against the L1210 murine leukaemia or Walker rat carcinosarcoma cells in culture. The results are consistent with the possibility that calmodulin is important to the functioning of oestrogen receptor mediated growth in MCF-7 cells.
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PMID:Variation of the inhibition of calmodulin dependent cyclic AMP phosphodiesterase amongst analogues of tamoxifen; correlations with cytotoxicity. 216 3

The pathological changes characteristically observed in the kidney, bone marrow, thymus, spleen, and duodenum of the rat given 12.2 mg/kg of cis-platinum (CDDP) ip are reduced or eliminated when a CDDP solution containing a 20-fold excess of L-methionine to cis-platinum is administered. L-Methionine was also effective in reducing the renal toxicity induced by CDDP when given orally 20 min before the iv administration of 7.5 mg CDDP/kg. L-Methionine did not compromise the efficacy of CDDP when the antitumor activity of the combination of L-methionine and CDDP was measured against the Walker 256 carcinosarcoma in the rat. No significant reduction in the antitumor activity of the CDDP resulted from the parenteral administration of L-Methionine when evaluated against the L1210 murine leukemia. The oral administration of L-methionine (500 mg/kg) 30 min after the administration of CDDP has no significant effect on the antitumor activity of CDDP in mice bearing the L1210 murine leukemia. The results suggest that L-methionine may have some practical utility in the control of certain aspects of CDDP toxicity.
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PMID:L-methionine suppresses pathological sequelae of cis-platinum in the rat. 234 Sep 84

The antitumor activity of a few 1-nitro-9-aminoacridine derivatives including nitracrine was evaluated against ascitic forms of murine tumors: Ehrlich carcinoma. Walker carcinosarcoma 256, and leukemia L1210. The studied compounds exhibited significant activity against ascitic Ehrlich carcinoma and very high activity against Walker carcinosarcoma. Leukemia L1210 on mice was not sensitive to the 1-nitro derivatives studied. On the basis of these results and the results reported earlier the following, specific biological properties exhibited by the derivatives studied were discussed: a) high activity against HeLa S3 and L1210 cells in vitro, but lack of activity against mice leukemia L1210; b) significant activity against some experimental and clinical tumors but not against leukemias, and c) lack of mammalian myelotoxicity.
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PMID:Antitumor activity of 1-nitro-9-aminoacridines including nitracrine against some ascitic experimental tumors. 235 49

Certain derivatives of phenolselenonic acid, namely ammonium, calcium, potassium, and sodium 3-acetoxy-4-methoxybenzolselenonates as well as the corresponding derivatives of 3-hydroxy-4-methoxybenzolselenonic acid were studied. These compounds were tested for anticarcinogenic activity against urethane-induced pulmonary adenomas and for antitumoral activity against some transplanted tumours such as leukemia L 1210, mammary adenocarcinoma Ca 755 and Walker carcinosarcoma 256. These compounds were found to produce more intensive anticarcinogenic action than antitumoral one. The results showed that ammonium 3-acetoxy-4-methoxybenzolselenonate given before the injection of urethane or together with urethane exert a significant influence on adenomas, while calcium 3-hydroxy-4-methoxybenzolselenonate inhibited the formation of adenomas at various stages of their development.
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PMID:[Anticarcinogenic and antitumor properties of selenium-containing phenol derivatives]. 324 98

MX-2, a new morpholino anthracycline derivative, showed broad anti-neoplastic activity against experimental tumors. Molecular weight of MX-2 is 622.07, and it can cross blood-brain barrier because of its high lipid solubility. In this report, we described its in vitro and in vivo effects on brain tumors. The growth of rat 9L and human KNS-42 glioma cells were markedly inhibited by the medium containing more than 1 ng/ml of MX-2. The inhibitory concentration of MX-2 for 50% cell kill was 1.8 ng/ml for 9L cell and 18 ng/ml for KNS-42, respectively. These values were the almost same as those reported with P388 leukemia. In rats with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells, the median survival time was significantly prolonged. The increased life span was 40, 40, 40 (p less than 0.01), and 20% (p less than 0.05) in the animals given intravenous MX-2 of 1.5, 1.0, 0.75, and 0.375 mg/kg on day 1, 5, and 9 after tumor inoculation respectively. These results indicate that MX-2 may be a promising new antineoplastic agent for the treatment of malignant brain tumor.
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PMID:[Effect of MX-2, a morpholino anthracycline derivative, against human and rat glioma cells and experimental leptomeningeal tumors in rats]. 336 70

A novel nitrosourea, 1-(2-chloroethyl)-3-[2-(dimethylaminosulfonyl) ethyl]-1-nitrosourea (TCNU) tauromustine, has been investigated in a broad anti-tumour screen and, in depth toxicology and initial pharmacokinetics carried out. TCNU and its two metabolites were found to exhibit equal or better oral efficacy than that of BCNU, CCNU, MeCCNU or chorozotocin against L1210 leukemia, Walker mammary carcinoma, Lewis Lung, Harding Passey melanoma and colon carcinoma C26. The toxicological profile of TCNU after acute and 3 months treatment was similar in mice and rats to that of CCNU, with the exception that, TCNU did not cause the chronic liver disturbances found for CCNU. In dogs treated for 6 weeks with TCNU leucopenia and thrombocytopenia were the major side effects. Parent TCNU was found in all dogs. The absorption was fast, the maximum level being reach after 25 mins and the mean absorption time was 22 mins. The mean half life was 16.1 mins after intravenous and 17.4 after oral administration. The combination of these factors make TCNU an interesting clinical candidate.
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PMID:Anti-tumour, toxicological and pharmacokinetic properties of a novel taurine-based nitrosourea (TCNU). 341 Jun 63


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