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)

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 series of hydrazine derivatives was tested for antineoplastic activity. Cyanoacetic acid hydrazide (I), cyanoacetic acid methylhydrazide (II) and N-thioamido-N'-cyano-acethylhydrazine (VI) appeared to be the most active agents against sarcoma 180, Ehrlich carcinoma and Nemeth Kellner lymphoma. The maximum tumor weight inhibition ranged from 70 to 90%. N, N'-bis-cyano-acethylhydrazine (IV) and N-isonicotinoyl-hydrazine (VIII) showed significant antitumor activity in Ehrlich carcinoma and Nemeth Kellner lymphoma systems. None of hydrazine derivatives were active against L1210 leukemia. The most active agents, I, II and VI were further evaluated in leukemia P388, melanoma B16, Lewis lung carcinoma and mammary carcinoma 16/C, and the agent VI was additionally tested in plasmacytoma MP26, colon carcinoma 26 abd Walker carcinosarcoma 256 systems. However, there was no effect with any agent or dose tested against any neoplasm.
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PMID:Antineoplastic activity of new linear hydrazine derivatives. 344 37

Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the hypocalcemic effects.
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PMID:Gallium nitrate: the second metal with clinical activity. 353 51

The disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid (I) used in the mg/kg dose decreases the cyclophosphane toxicity in mice and potentiates the cytostatic activity of cyclophosphane, 5-fluorouracil and arabinosyl cytosine against leukemia P388, murine sarcoma 37 and Walker's carcinosarcoma. Administered alone I exhibits no antitumour activity. The potentiation of the antitumour effect of drugs appears independent of the administration schedule. Biochemical evidence indicates that I does not block DNA synthesis in leukemic cells in vitro, but significantly enhances the DNA-blocking effect of cyclophosphane in the same cells in vivo.
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PMID:[Potentiating effect of disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid on the activity of various antitumor agents]. 358 40


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