Abstract：
:4'-Deoxydoxorubicin (4'-deoxy) is a new adriamycin analogue with a similar spectrum of antitumour activity but is significantly more lipophilic than the parent compound. We report the kinetics and uptake of the two drugs by human non-small cell lung tumour cells in monolayer culture and the relationship between intracellular drug levels and cytotoxicity. The rate and degree of cell uptake of 4'-deoxy (Vmax = 30 ng/10(5) cells/min) was greater than that of adriamycin (Vmax = 0.15 ng/10(5) cells/min). Although for a given intracellular drug concentration adriamycin was more lethal, on the basis of extracellular drug concentration, cell kill was virtually identical. The log cell survival vs intracellular drug concentration plot was linear for adriamycin but biphasic for 4'-deoxy. Intracellular distribution of the two drugs was followed by fluorescent microscopy and it was apparent that adriamycin was localized mainly within the nucleus whereas 4'-deoxy accumulated within the cytoplasm. Our results suggest that the relationship between intracellular distribution of the two drugs could reflect different modes of action for the drugs with respect to binding sites or could be a non-specific phenomenon, unrelated to lethal effects.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Kerr DJ,Kerr AM,Freshney RI,Kaye SBdoi
10.1016/0006-2952(86)90195-4subject
Has Abstractpub_date
1986-08-15 00:00:00pages
2817-23issue
16eissn
0006-2952issn
1873-2968pii
0006-2952(86)90195-4journal_volume
35pub_type
杂志文章abstract：:The effects of tuamine (1-methylhexylamine), a sympathomimetic compound with hypertensive properties, heptaminol (6-amino-2-methyl-2-heptanol), an aliphatic amine with pressor properties, and two structural analogues of tuamine on high-affinity Na(+)-dependent noradrenaline uptake and on nicotine-evoked release were e...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90322-c
更新日期：1990-08-15 00:00:00
abstract：:The effect of 2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)- 6-isopropoxy-4(3H)-quinazolinone hydrochloride (MCI-176), a calcium antagonist, on ischemic myocardial metabolism was studied in dog hearts subjected to an occlusion of the left anterior descending coronary artery (LAD) for 3 or 30 min. MCI-176 (0.0...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90543-e
更新日期：1991-02-01 00:00:00
abstract：:Glyburide is a second-generation sulfonylurea hypoglycemic drug used for the treatment of select women with pregestational and gestational diabetes mellitus (GDM). In vitro and in vivo investigations demonstrated its very low transplacental transfer to the fetal circulation. However, the factors influencing its low tr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.05.019
更新日期：2006-08-28 00:00:00
abstract：:Resistance to anti-cancer chemotherapies often leads to regional failure, and can be caused by biochemical and/or physiological mechanisms. Biochemical mechanisms include the overexpression of resistance-conferring proteins. In contrast, physiological resistance involves the tumor microenvironment, and can be caused b...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00467-2
更新日期：2003-10-01 00:00:00
abstract：:Cyclic guanosine 3'-5'-monophosphate (cGMP) has recently been shown to constitute a second messenger for Xenopus laevis melatonin Mel1c receptors. To verify whether cGMP levels are also modulated by mammalian melatonin receptors, we cloned the genes encoding the human Mel1a and Mel1b receptor subtypes and expressed th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00134-3
更新日期：1999-08-15 00:00:00
abstract：:Male mice were exposed via their diet to perfluoro fatty acids of various chain-lengths (2-10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2-10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial pro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90383-t
更新日期：1992-09-25 00:00:00
abstract：:Glucuronidation of quinols of polycyclic aromatic hydrocarbons (PAHs) represents an important detoxication pathway preventing toxic quinone/quinol redox cycles. Therefore, mono- and diglucuronide formation of benzo(a)pyrene-3,6-quinol was investigated and compared to that of structurally related 3,6-dihydroxychrysene ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00095-h
更新日期：1995-05-26 00:00:00
abstract：:The current obesity epidemic is a major worldwide health and economic burden. In the modern environment, an increase in the intake of high-fat and high-sugar foods plays a crucial role in the development of obesity by disrupting the mechanisms governing food intake and energy balance. Food intake and whole-body energy...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.07.008
更新日期：2018-09-01 00:00:00
abstract：:The cellular distribution of AcCoA:arylamine N-acetyltransferase (NAT; EC 2.3.1.5) activities was examined in the rat small intestine to determine if heterogeneous cellular distribution contributes to preferential tumor development in the colonic region after exposure to heterocyclic amines (HAs). A chelation/elution ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00659-x
更新日期：1998-05-01 00:00:00
abstract：:β1-Adrenergic receptor (β1-AR) agonists and antagonists are widely used in the treatment of major cardiovascular diseases such as heart failure and hypertension. The β1-AR like other G protein-coupled receptors (GPCRs) are endocytosed in response to intense agonist activation. Recycling of the agonist-internalized β1-...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.09.011
更新日期：2016-11-15 00:00:00
abstract：:Eighteen linear analogues of [Arg8]vasopressin (AVP) were synthesized by systematically substituting the cysteine residues at positions 1 and 6 with a range of L-amino acids. Screening by competition ligand binding revealed that the combinations of amino acid residues tolerated at these positions was very restricted w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90523-1
更新日期：1994-04-29 00:00:00
abstract：:Most in vivo studies demonstrating decreased activities of hepatic cytochromes P450 with inflammation have used Gram-negative bacterial lipopolysaccharide (LPS) as the inflammatory stimulant. But products of Gram-positive bacteria, such as staphylococcal enterotoxin B (SEB), also stimulate inflammatory mediators, albe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00250-1
更新日期：2000-05-15 00:00:00
abstract：:Stroke is a neurological condition and may cause changes in hepatic drug-metabolizing enzymes. Hepatic CYP2B is involved in the metabolism of a variety of centrally active substances. The purpose of this study was to investigate the possible down-regulation mechanism of hepatic CYP2B after acute stroke. Using a rat mo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.12.011
更新日期：2014-02-15 00:00:00
abstract：:The effect of macrophage supernatant on the recovery of wounds induced in rat gastric epithelial RGM1 monolayers was investigated. The repair of wounds induced in the monolayers of RGM1 cells was accelerated time-dependently by 10 ng/mL of transforming growth factor-alpha (TGF-alpha). TGF-alpha also significantly stim...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00202-6
更新日期：1999-10-01 00:00:00
abstract：:N,N-Dimethyl-D-erythro-sphingosine (DMS) is the N-methyl derivative of sphingosine; both are activators of sphingosine-dependent protein kinases. The aim of this work was to study the effect of DMS on cytosolic calcium and intracellular pH (pHi) in human T lymphocytes. The variations of calcium and pH were determined ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01519-8
更新日期：2003-02-01 00:00:00
abstract：:The abilities of the naturally occurring polyamines, putrescine, spermidine and spermine, to affect variables related to the bioenergetic functions of isolated rat liver mitochondria were studied. At concentrations comparable to those present intracellularly, the polyamines inhibited state 4 respiration, but they had ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90654-2
更新日期：1982-12-15 00:00:00
abstract：:The population growth rate of HeLa cells treated with 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) in reinforced Eagle's minimum essential medium was directly related to the concentration of fetal bovine serum in the range from 5 to 30%. Control cells proliferated at a maximal rate (doubling time: ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90306-x
更新日期：1984-02-15 00:00:00
abstract：:The triazolobenzodiazepine compound alprazolam may have unique clinical effects compared to other benzodiazepines, and both behavioral and neurochemical studies have indicated unusual results after acute doses of alprazolam. To determine the effects of chronic dosage in mice, alprazolam (2 mg/kg/day) was administered ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90584-4
更新日期：1989-11-01 00:00:00
abstract：:Aminoglycoside antibiotics induce a lysosomal phospholipidosis in kidney proximal tubules after conventional therapy in animals and man. We have previously demonstrated that these drugs bind to negatively charged phospholipid bilayers at acid pH and inhibit the activity of lysosomal acid phospholipases in vitro and in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90607-0
更新日期：1985-04-01 00:00:00
abstract：:Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released from KS and host cells and HIV viral products-the protein Tat are reported to be involved in angiogenesis. Mounting evidence further suggests that m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.06.012
更新日期：2007-11-01 00:00:00
abstract：:An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2013.12.014
更新日期：2014-04-15 00:00:00
abstract：:Pancreatic stellate cells (PSCs) play a key role in pancreatic fibrosis, a constant feature of chronic pancreatitis. PSC activation occurs in response to profibrogenic mediators such as cytokines and involves proliferation, transition towards a myofibroblastic phenotype and enhanced production of extracellular matrix ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00075-3
更新日期：2003-04-15 00:00:00
abstract：:Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.08.001
更新日期：2006-11-15 00:00:00
abstract：:The effect of 5 consecutive daily i.p. doses of CPZ (5 mg/kg), PZ (10 mg/kg) and PMZ (10 mg/kg) on the activity of kynurenine hydrolase and kynurenine aminotransferase in mouse liver was studied. All three phenothiazines effected an increase in the activity of kynurenine hydrolase per unit weight of liver with CPZ sho...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90105-8
更新日期：1982-07-01 00:00:00
abstract：:SARM is the fifth and most conserved member of the Toll/Il-1 Receptor (TIR) adaptor family. However, unlike the other TIR adaptors, MyD88, Mal, TRIF and TRAM, SARM does not participate in transducing signals downstream of TLRs. By contrast SARM inhibits TLR signalling by interacting with the adaptors TRIF and MyD88. I...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2019.01.005
更新日期：2019-03-01 00:00:00
abstract：:We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and prolifer...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.11.001
更新日期：2017-02-01 00:00:00
abstract：:The effect of non-insulin-dependent diabetes on the hepatic microsomal cytochrome P450-dependent mixed-function oxidase system and on cytosolic glutathione S-transferase activity was determined using the spontaneously obese-diabetic (ob/ob) mouse model. The activities of the xenobiotic-metabolizing cytochrome P450 pro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90724-w
更新日期：1992-04-15 00:00:00
abstract：:Reactive oxygen and nitrogen species are overproduced in the cardiovascular system in response to the exposure to doxorubicin, a cardiotoxic anticancer compound. Oxidant-induced cell injury involves the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and pharmacological inhibition of PARP has recen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.11.023
更新日期：2005-03-01 00:00:00
abstract：:MRS 1754 [N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy]acetamide] is a selective antagonist ligand of A(2B) adenosine receptors. This is the least well-defined adenosine receptor subtype, and A(2B) antagonists have potential as antiasthmatic drugs. For use as a radioligand, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00531-7
更新日期：2001-03-15 00:00:00
abstract：:Glycerol enhances pulmonary tumorigenesis in mice treated with 4-nitroquinoline 1-oxide (4NQO). The present study shows that active oxygen formation by glycerol may be responsible for this enhanced tumorigenesis. Male ddY mice were treated with 4NQO and given a 5% glycerol solution instead of drinking water for up to ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90156-d
更新日期：1992-06-23 00:00:00
