Abstract：
:The oxazaphosphorine agent cyclophosphamide (CP) is an alkylating agent with a relative low stem cell toxicity. The aim of this study was to further evaluate the stem cell toxicity of the active metabolites of CP and its structural analogue ifosfamide (IFO) in comparison to their antileukemic efficacy. Cells of different malignant hematologic disorders (HL-60, HS-Sultan and THP-1) and CD34+ stem cells were treated with cytotoxic CP-metabolite mafosfamide (MAFO) and IFO-metabolites 4-hydroxy-IFO (4-OH-IFO) and chloroacetaldehyde. The clonogenity of the cells was investigated by using a colony-forming assay. All metabolites reduced the formation of both tumor-derived colonies and stem cell-derived CFU-GMs in a concentration-dependent manner. Our data showed a relative tumor-specific, stem cell protecting action of the substances tested with a higher toxicity against tumor cells (IC(50) against HS-Sultan: MAFO 1.1 microM; 4-OH-IFO 1.3 microM; CAA 3 microM) than against stem cells (IC(50) MAFO 14.8 microM; 4-OH-IFO 16.9 microM; CAA 14 microM). However, while the cytotoxic action of 4-OH-IFO corresponded to MAFOs activity, CAAs cytotoxic effect against the hematologic tumor cells was lower. In conclusion, the results confirm the observed cytotoxicity of CAA against solid tumors for cells of malignant hematologic disorders. Although the relative cytotoxic specificity of CAA is lower than for 4-OH-IFO and MAFO, also CAA, like 4-OH-IFO and MAFO, was found to be in part a tumoricidal, stem cell protecting substance.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Brueggemann SK,Schlenke P,Klich S,Deeken M,Peters SO,Wagner Tdoi
10.1016/s0006-2952(02)00868-7subject
Has Abstractpub_date
2002-04-01 00:00:00pages
1337-41issue
7eissn
0006-2952issn
1873-2968pii
S0006295202008687journal_volume
63pub_type
杂志文章abstract：:Snake venom three-finger α-neurotoxins (α-3FNTx) act on postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of membrane rec...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114168
更新日期：2020-11-01 00:00:00
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journal_title：Biochemical pharmacology
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doi：10.1016/0006-2952(86)90220-0
更新日期：1986-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.09.021
更新日期：2015-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90070-0
更新日期：1987-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90203-h
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90525-n
更新日期：1992-10-06 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.02.024
更新日期：2013-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90099-q
更新日期：1991-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90189-4
更新日期：1993-06-09 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.08.011
更新日期：2011-12-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90459-x
更新日期：1987-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90399-0
更新日期：1986-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90549-1
更新日期：1987-08-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.06.028
更新日期：2018-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90455-0
更新日期：1983-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113936
更新日期：2020-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.07.001
更新日期：2008-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90390-5
更新日期：1988-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00023-s
更新日期：1995-06-16 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90074-6
更新日期：1983-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90068-x
更新日期：1994-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90046-1
更新日期：1983-06-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(03)00145-x
更新日期：2003-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90006-1
更新日期：1985-08-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90344-7
更新日期：1984-06-01 00:00:00
abstract：:H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.12.013
更新日期：2019-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00252-u
更新日期：1995-10-12 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90155-2
更新日期：1984-11-15 00:00:00
abstract：:Foetal rat whole brain reaggregate cultures were prepared in a serum-supplemented (S+) or serum-free medium (S-). Ethylcholine mustard aziridinium (ECMA) was added to the cultures at 9 days in vitro (DIV) at concentrations of 12.5, 25 or 50 microM. Choline acetyltransferase (ChAT) activity was measured at +2, +48 and ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90311-0
更新日期：1989-05-15 00:00:00
abstract：:Chronic treatment with a low dose of reserpine (0.1 mg/kg) caused rats to become hyperactive in the "open field" apparatus. When mianserin (5 mg/kg) or the selective serotonin uptake inhibitor ORG. 6582 (5 mg/kg) was chronically administered in combination with reserpine, the hyperactivity was attenuated. Both antidep...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90329-5
更新日期：1983-05-15 00:00:00
