Abstract:
:Doxorubicin is shown to be present in albumin microspheres (10-40 microns) in two forms: the native drug and a fraction of drug covalently coupled to the protein matrix probably via glutaraldehyde. Upon trypsin digestion the fraction covalently coupled is released and can be resolved from native doxorubicin by high performance liquid chromatography and quantitated either by using 14C-labelled doxorubicin or by measuring the absorption of the doxorubicin chromophore at 480 nm. Albumin microspheres contained 6.9 micrograms/mg protein covalently bound drug versus 11.1 micrograms/mg native drug when 1% glutaraldehyde was used in microsphere preparation. The covalently bound fraction increased significantly with 2% glutaraldehyde. Albumin/polyaspartic acid microspheres lacked a covalently bound fraction when prepared under the same conditions as pure albumin microspheres (35 micrograms/mg native drug, 1% glutaraldehyde) but transferrin microspheres contained similar amounts of bound and native albumin. In vivo, albumin microspheres altered the disposition of doxorubicin in a rat mammary carcinoma (Sp107) compared to albumin/polyaspartic acid microspheres by reducing the rate of parent drug elimination from the tumour and by reducing its biotransformation to 7-deoxyaglycone metabolites. These data indicate that covalent coupling is a key component in the way doxorubicin is handled in tumours after administration of protein microspheres.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Cummings J,Willmott N,Marley E,Smyth Jdoi
10.1016/0006-2952(91)90123-msubject
Has Abstractpub_date
1991-06-15 00:00:00pages
1849-54issue
12eissn
0006-2952issn
1873-2968pii
0006-2952(91)90123-Mjournal_volume
41pub_type
杂志文章abstract::In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the ef...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90180-5
更新日期:1993-02-24 00:00:00
abstract::The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk-cell differentiation in the cellular slime mould Dictyostelium discoideum. It has also been shown that DIF-1 and its derivative (DIF-3) suppress cell growth in mammalian tumor cells. In the prese...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.06.002
更新日期:2005-09-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90615-p
更新日期:1992-03-03 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00710-9
更新日期:2001-09-01 00:00:00
abstract::Dimercaptosuccinic acid (DMSA) was shown to lower blood pressure in rat models of arterial hypertension. Thus, there is evidence that-besides its chelating properties-DMSA has a direct vascular effect, e.g. through scavenging of reactive oxygen species (ROS). We speculated that, in addition, intracellular calcium mobi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00121-7
更新日期:2003-05-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.09.025
更新日期:2012-01-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00600-1
更新日期:2001-06-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.05.003
更新日期:2016-07-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90574-9
更新日期:1983-03-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:1999-01-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.08.020
更新日期:2016-10-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90047-3
更新日期:1983-06-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.07.026
更新日期:2012-10-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.12.003
更新日期:2011-03-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90314-4
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90541-4
更新日期:1993-08-17 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90572-2
更新日期:1988-06-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:2020-02-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90243-5
更新日期:1983-10-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.113941
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:10.1016/0006-2952(94)00385-8
更新日期:1994-12-16 00:00:00
abstract::The role of Ca2+ and protein kinase C (PKC) activity in the release of immunoreactive endothelin-1 (ET-1) from cultured porcine aortic endothelial cells of first or second passage has been studied. ET-1 accumulation within cells and secretion into cell-conditioned medium over 3 and/or 5 hr was measured. Confluent cell...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
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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(86)90355-2
更新日期:1986-02-15 00:00:00
abstract::The orphan nuclear receptor estrogen-related receptor alpha (ERRalpha) has been implicated in the development of various human malignancies, including breast, prostate, ovary, and colon cancer. ERRalpha, bound to a co-activator protein (e.g., peroxisome proliferator receptor gamma co-activator-1alpha, PGC-1alpha), reg...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.05.024
更新日期:2010-09-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:2018-05-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00670-9
更新日期:1998-05-15 00:00:00
abstract::The deamination of 5-hydroxytryptamine, tryptamine and benzylamine by porcine dental pulp membrane preparations is brought about not only by monoamine oxidase, but also by a clorgyline (and deprenyl) resistant), semicarbazide sensitive enzyme. The semicarbazide sensitive enzyme was also inhibited by aminoguanidine, hy...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90127-7
更新日期:1982-09-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90353-9
更新日期:1986-02-15 00:00:00
abstract::Cathepsin K is a cysteine protease that degrades type I human collagen during bone resorption. We have expressed the recombinant human cathepsin K in Chinese hamster ovary (CHO) cells as a pre-proenzyme and demonstrated that it is processed intracellularly to an active enzyme form and that only the proenzyme form is s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00381-6
更新日期:2000-09-15 00:00:00