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)

Phytochemical examination of the underground parts of Ruscus aculeatus has led to the isolation of a total of twelve steroidal saponins, including seven new ones. The structures of the new saponins were determined by spectroscopic analysis and chemical evidence. The furostanol saponin, having a diglycoside moiety modified with a (2S,3S)-2-hydroxy-3-methylpentanoic acid group and an acetic acid group, and its corresponding spirostanol saponin exhibited cytostatic activity on leukemia HL-60 cells.
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PMID:New steroidal constituents of the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells. 950 65

The authors studied the effect of two modified steroids containing different proportions (%) of alkylating agents alone or in combination on sister chromatid exchange (SCE) rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The two chemicals in mixtures enhance SCE induction and antitumor activity in a synergistic manner. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenyl acetic acid was found to be more effective than the homo-aza-steroidal ester of o-bis(2-chloroethyl)aminobenzoic acid in causing cytogenetic damage and antineoplastic activity. A correlation was observed between the magnitude of the SCE response and the depression of the cell proliferation index. The order of the antitumor effectiveness of the five different treatments tested coincided with the order of the cytogenetic effects they induced.
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PMID:Enhanced cytogenetic and antineoplastic effects by the combined action of two esteric steroidal derivatives of nitrogen mustards. 987 11

To determine the incidence of leukemia-specific rearrangements, 60 cases of childhood acute myeloblastic leukemia and transient myeloproliferative disorder were screened with a novel multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and the results were correlated with the cytogenetic findings. The RT-PCR assay detects 28 different fusion genes and more than 80 different fusion transcript variants. RNA was isolated from methanol/acetic acid-fixed cells that had been routinely prepared for cytogenetic analysis. Nine different fusion transcripts were found in 40% of the cases, whereas 78.3% of the cases had abnormal karyotypes. Two cases with a t(6;11) and an MLL/AF6 gene fusion were missed cytogenetically. Conversely, cytogenetic analysis revealed 10 other well-defined chromosome rearrangements. Although cytogenetic analysis reveals a much broader range of abnormalities, multiplex RT-PCR serves as quality control and provides the essential information for minimal residual disease studies. Moreover, discrepant findings lead to the detection of new rearrangements on the molecular genetic level.
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PMID:Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia. 1115 1

The monoclonal antibodies, 9.2.27 against human melanoma cell lines and WM53 against leukemia cell lines, were conjugated with cyclic anhydride gadolinium-diethylenetriaminepenta-acetic acid (Gd-cDTPAa) and used as tumor-specific contrast agents in magnetic resonance imaging (MRI). The data indicate that Gd-DTPA-9.2.27 in solution decreased the T1 relaxation of water protons at 7.0 Tesla (300 MHz) in direct proportion to the gadolinium concentration, and this effect was greater than in Gd-DTPA solutions. These conjugates show high specificity for melanoma and leukemia cell lines. T1 relaxation time at 7.0 Tesla, measured for the melanoma cell line (MM-138) and leukemia cell line (HL-60) after incubation at 37 degrees C for 4 hr, were significantly decreased (approximately 25%) relative to controls. The gadolinium concentration in cells and washing solutions was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES). A linear relationship was observed between T1 relaxation rates and gadolinium concentrations obtained by ICP-AES. The ICP-AES results showed no gadolinium uptake in the non-targeted HT-29 colorectal cancer cells.
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PMID:In vitro studies of gadolinium-DTPA conjugated with monoclonal antibodies as cancer-specific magnetic resonance imaging contrast agents. 1204 73

Reaction of antitumor agent irofulven (1) with zinc and acetic acid yielded several new indene derivatives (6, 7, 8, 10) as well as the known indene (9). These all have greatly reduced toxicity to human leukemia (HL60) cells compared to irofulven.
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PMID:Reaction of irofulven with zinc and acid. 1260 75

A series of nonconventional aminium N-(6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamidates 7-15 have been synthesized by the reactions of 6-chloro-7-R-3-methylthio-1,4,2-benzodithiazine 1,1-dioxides with 4-dimethylaminopyridine or Et(3)N and some arylsulfonamides. The free N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)benzenesulfonamides 16-18 were obtained by treatment of their aminium salts with H(2)SO(4) in boiling acetic acid. The in vitro antitumor activity of the compounds 9, 11-14 and 16-18 has been tested in the antitumor screening of the National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. 4-Dimethylaminopyridinium 4-chloro-N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)benzenesulfonamidate 9 is the prominent of the compounds due to its remarkable activity (log GI(50)<-8.00, log TGI=-5.50) and selectivity for the leukemia SR cell line. For that reason experimental and theoretical analysis of the geometric and electronic properties of 9 was carried out.
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PMID:Synthesis, structural characterization and in vitro antitumor activity of novel 6-chloro-1,1-dioxo-1,4,2-benzodithiazie derivatives. 1290 13

3-(1-Phenyl-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones 14a-q and 15a-q were synthesized by refluxing in acetic acid the corresponding 2-methylquinazolinones 12 and 13 with the opportune benzoic aldehyde for 12 h. The synthesized styrylquinazolinones 14a-q and 15a-q were tested in vitro for their antileukemic activity against L1210 (murine leukemia), K562 (human chronic myelogenous leukemia) and HL60 (human leukemia) cell lines showing in some cases good activity.
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PMID:Synthesis and antileukemic activity of new 3-(1-phenyl-3-methylpyrazol-5-yl)-2-styrylquinazolin-4(3H)-ones. 1498 85

Increased clinical applications of the anticancer drug etoposide (a non-intercalative epipodophyllotoxin derivative) and the frequent induction of a second malignancy, particularly leukaemia, in post-etoposide-treated cancer survivors warrant detailed genotoxicity testing of etoposide. The genotoxicity test results available on etoposide are either primarily in in vitro test systems or in lower organisms after treatment with unusually high doses, or after chronic exposures, having little extrapolative value to humans. Therefore, a cytogenetic risk assessment study on etoposide in mouse in vivo was undertaken after a low dose (in accordance with the human therapeutic dose) single exposure. The cytogenetic toxicity of etoposide was assessed from bone marrow of mouse at three separate endpoints: chromosomal aberration and mitotic index studies at 24 h post-treatment and the micronucleus test (MNT) at 30 h post-treatment. The flame drying technique using colchicine, hypotonic sodium citrate, methanol-glacial acetic acid and Giemsa was followed for the preparation of slides for the metaphase chromosomal aberration and mitotic index studies and a simple technique was followed for the MNT. Although induction of chromosomal aberrations, excluding gaps, per 100 metaphases by 10 and 15 mg kg(-1) etoposide was not significant statistically, 20 mg kg(-1) of etoposide induced a significantly higher number of chromosomal aberrations in female (P < or = 0.01) and male (P < or = 0.05) mice. There was no significant change in the induced percentages of dividing cells by any of the doses of etoposide tested. The micronucleus induction also was not significant statistically with the lowest dose but it was significant in female (P </= 0.01) and male (P </= 0.05) mice that received 15 mg kg(-1) etoposide and was highly significant (P </= 0.01) in both female and male mice that received 20 mg kg(-1) etoposide. The results indicated the clastogenic action of etoposide in mouse bone marrow after a single treatment with such low doses. However, the drug did not interfere with cell cycle progression. Although it is a DNA-non-intercalating agent, etoposide is known for its interference in the activity of DNA topoisomerase IIalpha enzyme, particularly in the proliferative cells where the concentration and activity of the enzyme are greater. This might be the reason for the induction of leukaemia in post-etoposide-treated cancer survivors. Therefore, it has become absolutely necessary to make etoposide target-specific, i.e. specific to the topoisomerase II enzymes of cancerous cells.
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PMID:Cytogenetic risk assessment of etoposide from mouse bone marrow. 1505 6

In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 microg ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC(50) value of 5.8 versus 3.2 microM for colchicine. It was also examined for effects on the growth of human MCF7 breast carcinoma cells and Burkitt lymphoma CA46 cells, which had IC(50) values of 0.34 and 1.0 microM, respectively. At 10 microM 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone induced G2/M arrest (66%) in Burkitt cells, with a mitotic index of 20%. At 3.4 microM, it caused disruption of the cellular microtubule system of the MCF7 cells. Both these cellular effects are consistent with its mechanism of action resulting from its inhibitory effect on tubulin assembly.
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PMID:Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones. 1507 39

3-(3-Methylisoxazol-5-yl) and 3-(pyrimidin-2-yl)-2-styrylquinazolin-4(3H)-ones 8a-l and 9a,c-e,h-l were synthesized by refluxing in acetic acid the corresponding 2-methylquinazolinones 6 and 8 with the opportune benzoic aldehyde for 12 h. The synthesized styrylquinazolinones 8a-l and 9a,c-e,h-l were tested in vitro for their antileukemic activity against L-1210 (murine leukemia), K-562 (human chronic myelogenous leukemia) and HL-60 (human leukemia) cell lines showing in some cases good activity.
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PMID:Synthesis and antileukemic activity of new 3-(5-methylisoxazol-3-yl) and 3-(pyrimidin-2-yl)-2-styrylquinazolin-4(3H)-ones. 1517 7


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