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 antitumor properties of (E)-2-(fluoromethyl)dehydroornithine methyl ester (delta-MFMO-ME) and of (E)-2-(fluoromethyl)dehydroornithine ethyl ester (delta-MFMO-EE), the prodrugs of delta-MFMO, an irreversible inhibitor of mammalian L-ornithine decarboxylase (ODC) 14 times more potent than alpha-difluoromethylornithine (DFMO) and equipotent to (2R,5R)-6-heptyne-2,5-diamine (MAP) in vitro, have been investigated in L1210 leukemia- and Lewis lung carcinoma-bearing mice. The anticancer properties of these esters have been compared with those of DFMO and MAP as a function of the dose, the route of administration, and the stage of the lewis lung carcinoma development in mice. The two esters, administered i.p. shortly after cell inoculation at one-fifth the dose of DFMO, prolonged the survival of mice-bearing leukemia to the same extent as DFMO and MAP. When administered orally to leukemia-bearing mice the two esters were equipotent at prolonging survival. The methyl ester appears, however, to be slightly, but not significantly, more effective than the ethyl ester against leukemia when given i.p., maximum prolongation of the mice survival (79%) occurring at 0.5 g/kg methyl ester every 12 h. The two esters achieve at one-sixth to one-twelfth the dose, antitumor effects similar to DFMO in the Lewis lung carcinoma model, the ethyl ester being slightly, but not significantly, more effective than the methyl ester when administered orally. Moreover, the ethyl ester causes greater reduction of tumor growth than DFMO (P less than 0.05) and MAP (P less than 0.01) in this model. Inhibition of tumor growth is correlated with spermidine depletion and an increase of decarboxylated-S-adenosylmethionine, the aminopropyl donor in the spermidine and spermine synthase reactions. All ODC inhibitors, however, lose most of their antitumor properties when administered at late stage of Lewis lung carcinoma development. Finally, this study demonstrates the advantage of using prodrugs of delta-MFMO, an inhibitor of ODC, since they possess longer duration of action, higher potency, and in some cases better antitumor efficiency than the parent direct inhibitor of ODC. Moreover, and as already noticed for DFMO or MAP, no sign of overt toxicity is caused by the highest effective antitumor doses of the esters.
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PMID:Comparative antitumor properties in rodents of irreversible inhibitors of L-ornithine decarboxylase, used as such or as prodrugs. 250 Oct 26

4-amino-4-methyl-2-pentyne-1-al (AMPAL), a new irreversible inhibitor of aldehyde dehydrogenase (ALDH) has been assayed for its in vitro and in vivo antitumor activity. In vitro, AMPAL inhibits the proliferation and the ALDH activity of L1210 and RBL5 cell lines. In vivo, AMPAL significantly increases the mean survival time of mice i.p. grafted with leukemia (L1210, P815, MBL2, EL4, RBL5 cell lines) or carcinoma cells (Krebs cell line), without haematopoetic toxicity. No carcinostatic effect was observed against the P388 leukemia and the 3LL Lewis lung carcinoma. A possible relationship between the ALDH isoenzyme activity of the tumor and its sensitivity to AMPAL is discussed in the light of previous reports concerning the role of aldehydes in cell growth control.
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PMID:In vivo antitumor activity of 4-amino 4-methyl 2-pentyne 1-al, an inhibitor of aldehyde dehydrogenase. 251 73

[125I] Iodosulpride binding was examined on eight human cell lines derived from lung, breast and digestive tract carcinomas, neuroblastomas and leukemia. Specific binding was detected in five of these cell lines. In the richest cell line N417, derived from small cell lung carcinoma, [125I] iodosulpride bound with a high affinity (Kd = 1.3 nM) to an apparently homogeneous population of binding site (Bmax = 1,606 sites per cell). These sites displayed a typical D-2 specificity, established with several dopaminergic agonists and antagonists selective of either D-1 or D-2 receptor subtypes. In addition, dopamine, apomorphine and RU 24926 distinguished high- and low-affinity sites, suggesting that the binding sites are associated with a G-protein. The biological significance and the possible diagnostic implication of the presence of D-2 receptors on these cell lines are discussed.
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PMID:Presence of dopamine D-2 receptors in human tumoral cell lines. 252 31

Clomesone was evaluated for antitumor activity against a spectrum of animal tumor models. Clomesone exhibited significant antitumor activity against the murine L1210 leukemia implanted i.p., s.c., and intracerebrally (i.c.). Activity against s.c.-implanted tumor was largely independent of schedule and route of administration. Therapeutically optimal single-dose treatment (for tumored mice) was less toxic to nontumored mice than therapeutically optimal prolonged treatment. Clomesone also exhibited activity against other murine tumors (P388 leukemia, B16 melanoma, Lewis lung carcinoma, and M5076 sarcoma). It was active against P388 leukemia sublines resistant to cyclophosphamide, L-phenylalanine mustard, and cis-diamminedichloroplatinum(II). No activity was observed against a P388 subline resistant to N,N'-bis(2-chloroethyl)-N-nitrosourea or against Ridgway osteogenic sarcoma, a nitrosourea-resistant murine solid tumor. Clomesone is generally as effective as the chloroethylnitrosoureas against experimental tumor models. Since clomesone does not have the hydroxyethylating and carbamoylating activities of the chloroethylnitrosoureas (which do not appear to contribute to antitumor activity), it would likely be a more toxicologically selective compound. It may prove to be less carcinogenic than the chloroethylnitrosoureas, and it may contribute less target organ toxicity and less interference with the actions of other drugs when used in combinations.
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PMID:Antitumor activity of 2-chloroethyl (methylsulfonyl)methanesulfonate (clomesone, NSC 33847) against selected tumor systems in mice. 253 44

To investigate the characteristics in antitumor effects of 2-trimethylsilylethylthioethylamine(KAS-010) and its conjugate with 5-FU (KAS-011), the antitumor and immunomodulating activities of these silicon compounds were examined with various systems. Both KAS-010 and KAS-011 administered orally was found to be effective to B 16 melanoma, Meth A sarcoma and MM 46 mammary carcinoma in vivo. On the other hand, KAS-011 administered orally exhibited a marked antitumor activity against L 1210 leukemia bearing mice. Furthermore, these silicon compounds inhibited significantly metastases to the lymph nodes and lung of Lewis lung carcinoma implanted id into the right ear of BDF1 mice. Especially, KAS-011 in combination with tumor amputation resulted in a remarkable prolongation of the survival time (% ILS: 93.8%) in this antimetastatic model. The cell killing effect was mainly dependent on the exposure time of these silicon compounds in cultured KB and human lung cancer (OAT) cells. Moreover, a significant increase of delayed type hypersensitivity reaction (DTHR) to sheep red blood cell (SRBC) induced by KAS-010 was seen in old aged mice. The DTHR in B 16 melanoma and Ehrlich carcinoma bearing mice treated with KAS-010 was significantly higher than those of non-treated tumor bearing mice, indicating an enhanced cellular immunity to KAS-010 possibly resulting in a remarked antitumor effect. We also found that tumor free mice treated these silicon compounds were acquired specific tumor immunity to Meth A sarcoma and MM 46 mammary carcinoma.
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PMID:[Characteristics in antitumor effects of organic silicon related compounds]. 254 47

A new cytotoxic acridine alkaloid that exhibited antitumor activity in vivo was isolated from a marine Dercitus species sponge collected at a depth of 160 m in the Bahamas. This violet alkaloid, designated dercitin, inhibited the proliferation of cultured murine and human leukemia, lung, and colon tumor cells at nM concentrations (IC50 values of 63-150 nM) and prolonged the life of mice bearing ascitic P388 tumors (%T/C = 170, 5 mg/kg, i.p., QD1-9). Dercitin was also active against i.p. B16 melanoma and modestly inhibited the growth of s.c. Lewis lung carcinoma on the same schedule. DNA blocked the antiproliferative effects of the agent in culture, and incorporation studies indicated that dercitin disrupted DNA and RNA synthesis with less effects on protein synthesis, similar to the effects of known DNA intercalators. After 1-h exposure to 400 nM dercitin, the rates of incorporation of [3H]uridine, [3H]thymidine, and [3H]leucine by cultured P388 cells were inhibited 83, 61, and 23%, respectively. Equilibrium dialysis indicated that dercitin bound calf thymus DNA with an affinity of 3.1 microM and maximal binding of 0.20 mol dercitin/mol base pair. Binding involved intercalation as evidenced by ability to relax supercoiled phi X174 DNA (half maximal concentration for dercitin relaxation was 36 nM). The effects of dercitin on DNA mobility were reversible, and complete relaxation of DNA with topoisomerase I in the presence of dercitin followed by phenol extraction resulted in the appearance of supercoiled DNA. Dercitin, at microM concentrations, had a small effect in the K+-sodium dodecyl sulfate assay using cultured P388 cells, suggesting minimal inhibition of topoisomerase activity. But, dercitin completely inhibited DNA polymerase I/DNase nick translation of DNA at 1 microM. Relaxation of DNA at a given concentration was greater than inhibition of nick translation suggesting that the effects of dercitin on enzyme activity were secondary to changes in DNA conformation. Results indicate that dercitin is a new marine natural product that probably exerts its biological effects through intercalation into nucleic acids.
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PMID:Antitumor activity and nucleic acid binding properties of dercitin, a new acridine alkaloid isolated from a marine Dercitus species sponge. 254 17

Base propenals arise from DNA by a Fe(II)-bleomycin-mediated reaction which leads to strand scission. These compounds undergo addition-elimination reactions with thiols and other nucleophilic groups under physiological conditions and form an addition product with glutathione. Thymine- and adenine-N1-propenals inhibit DNA synthesis in HeLa cells; both compounds are cytotoxic [50% inhibiting concentration (IC50) = 1 to 2 microM]. A structurally related nucleoside, thymidine-N3-propenal, designed as a metabolic pathway inhibitor, inhibits growth of HeLa, L1210 leukemia, Lewis lung carcinoma, B16 melanoma, and DLD-1 human colon carcinoma cells in culture (IC50 = 1 to 6 microM). A single injection of this compound, administered on the first day following transplant of L1210 leukemia cells, increased the mean survival time of mice by 50% (T/C = 154). Thymidine-N3-propenal selectively blocks DNA synthesis in HeLa cells and inhibits thymidine kinase (Ki = 5.1 microM) and DNA polymerase-alpha. We suggest that base propenals, rather than damaged DNA, account for some of the cytotoxic effects of bleomycin and that nucleoside propenals represent a novel class of site-directed inhibitors.
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PMID:Origin and cytotoxic properties of base propenals derived from DNA. 257 72

Primary pulmonary cryptococcal granuloma is not common in Sichuan. The diagnosis of this disease is difficult to make because the patient has no characteristic symptoms and the chest X-ray findings of the mass are not easily differentiated from carcinoma of the lung. The incidence of this disease is apparently increasing. Pulmonary cryptococcosis may be disseminated hematogenously to the meninges and cryptococcal meningitis is very difficult to treat. If the pulmonary lesion is localized, the patient's general condition is good with no evidence of systemic lupus erythematosis, diabetes, leukemia or lymphoma, partial resection of the lung is indicated. But, if the patient has a history of recent cryptococcal meningitis, surgery must be deferred. Four cases of primary pulmonary cryptococcal granuloma have been treated surgically supplemented with medical therapy in the First Affiliated Hospital from 1986 to 1987. Follow-up of more than one year showed good results in each case.
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PMID:[Surgical treatment of primary pulmonary cryptococcal granuloma--report of 4 cases]. 259 37

A high antitumor activity of mitoxantrone dihydrochloride, synthesized according to a new method, was demonstrated in mice with i.p. growing tumors: P388 leukemia in CD2F1 and B16 melanoma in B6D2F1 hybrid strains. The preparation was ineffective when administered to mice with subcutaneously implanted solid tumors: Lewis Lung carcinoma, 16/C mammary adenocarcinoma or B16 melanoma. This finding is consistent with data reported by others for mitoxantrone produced by American Cyanamid Co. Acute toxicity of the tested compound was evaluated after single i.p. or i.v. administration to male and female CD2F1 and B6D2F1 mice.
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PMID:Biological evaluation of mitoxantrone dihydrochloride synthesized by a new method. I. Acute toxicity and antitumor activity in mouse transplantable tumor systems. 261 12

Published studies encompassing more than 50,000 autopsies were assessed to determine the sensitivity and specificity of clinical diagnostics (the diagnostic process) in persons dying of 1 of 11 specific diseases during the period 1930 through 1977. The accuracy of clinical diagnostics, as reflected in these two determinations, appeared to improve over this period with respect to some of the diseases studied (rheumatic heart disease and leukemia), while for others it worsened (pulmonary tuberculosis, peritonitis, carcinoma of the lung, gastric carcinoma, and carcinoma of the liver and extrahepatic biliary tract) and for a significant number diagnostic accuracy seemed refractory to sustained change (pulmonary embolism, primary cirrhosis of the liver, gastric/peptic ulcer, and acute coronary thrombosis/myocardial infarction). The findings suggest a new way in which the autopsy can be used to monitor clinical diagnostics to identify possible sources of systematic weaknesses and provide data that can be used to approach the difficult subject of necessary fallibility.
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PMID:The sensitivity and specificity of clinical diagnostics during five decades. Toward an understanding of necessary fallibility. 273 31


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