Abstract:
:5-Fluorouracil (FUra) has been administered to mice bearing xenografts of human colon adenocarcinomas. In two tumor lines, HxGC3 and HxVRC5, intrinsically resistant to FUra, 2'-deoxyuridylate (dUMP) accumulated 13.4- and 23.9-fold above basal levels. In HxELC2 xenografts, which demonstrated some sensitivity to FUra, there was a decrease in dUMP concentration after drug administration. Maximal intratumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) were found at 1 hr, but decreased in all tumor lines by 4 hr after administration of FUra. Data derived in tumor cytosols suggested that FdUMP levels in situ were not rate-limiting for formation of covalent ternary complex, but that accumulation of dUMP would retard the rate of complex formation. Subsequent to administration of FUra, thymidylate synthase activity was reduced greater than 75% in all tumors, but it recovered rapidly in tumors resistant to FUra. In addition, the pretreatment level of activity of thymidylate synthase was 12.7-fold greater in HxVRC5 tumors than in HxELC2 tumors. This elevated activity in HxVRC5 tumors appears not to be a consequence of gene amplification. Formation of FdUMP or the accumulation of dUMP did not correlate with the activity of phosphatases measured at pH 5.8 or pH 9.2 in each tumor line. Further, inhibition of phosphatase activity did not alter, significantly, the net rate of dissociation of the FdUMP-thymidylate synthase-[6R]-CH2-H4PteGlu complex.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Houghton JA,Weiss KD,Williams LG,Torrance PM,Houghton PJdoi
10.1016/0006-2952(86)90281-9subject
Has Abstractpub_date
1986-04-15 00:00:00pages
1351-8issue
8eissn
0006-2952issn
1873-2968pii
0006-2952(86)90281-9journal_volume
35pub_type
杂志文章abstract::The aim of this study was to document the in vivo transport of everolimus (inhibitor of mTOR) by P-glycoprotein (P-gp), and to investigate the influence of lapatinib (inhibitor of P-gp) on everolimus disposition. Pharmacokinetics of everolimus (0.25mg/kg) has been investigated after oral administration in mdr1a-/1b- m...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.02.013
更新日期:2009-05-15 00:00:00
abstract::The neuroprotective effects of adenosine are well-recognized. Recently, propentofylline, a xanthine derivative, has been shown to increase extracellular concentrations of adenosine in ischemic brain and to limit the extent of neuronal damage in experimental models of cerebral ischemia. Since the concentration of adeno...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90499-m
更新日期:1993-09-01 00:00:00
abstract::Purinergic stimulation of surfactant secretion via exocytosis of lamellar bodies is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers), nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00582-2
更新日期:2001-05-01 00:00:00
abstract::The metabolism of toluene in human liver microsomes and by cDNA-expressed human cytochrome P450s (CYPs) was investigated. Toluene was metabolized mainly to benzyl alcohol and slightly to o- and p-cresol by human liver microsomes. Formation of o-cresol was elevated in microsomes from human livers derived from cigarette...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00652-1
更新日期:1997-02-07 00:00:00
abstract::The cytoprotective effects of propylthiouracil (PTU) were studied in rats treated with the hepatotoxin D-galactosamine (D-GNH2). Five days of PTU pretreatment prior to D-GNH2 caused hypothyroidism and a significant reduction in liver injury as assessed by serum transaminase levels. When PTU was administered as a singl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90110-2
更新日期:1984-11-01 00:00:00
abstract::Binding of the selective D-1 dopamine receptor ligand 125I SCH 23982 was studied using crude plasma membranes derived from human renal cortex. 125I SCH 23982 bound saturably to a single high affinity site (Kd = 650 pM, Bmax = 19 fmol/mg protein). Binding at 37 degrees was rapid and reversible with forward and reverse ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90231-1
更新日期:1989-03-01 00:00:00
abstract::Anticholinesterases (anti-ChE) have some effects on biological properties including behavior, vision, and electroencephalograms, which are often long lasting and which do not appear to be due to cholinesterase (ChE; EC 3.1.1.7) inhibition, but which may be due to alterations in the organization and/or functioning of t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90460-m
更新日期:1991-09-12 00:00:00
abstract::The influence of delta 9-tetrahydrocannabinol (delta 9-THC) on the cellular levels of histone mRNAs and ribosomal RNAs was examined in several normal and transformed human cell lines--HeLa S3 cells, WI-38 human diploid fibroblasts, SV40-transformed WI-38 cells, and A549 lung carcinoma cells. RNA sequences were quantit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90510-0
更新日期:1984-04-01 00:00:00
abstract::A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-dip...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.10.015
更新日期:2012-01-15 00:00:00
abstract::This study demonstrates that a long-lasting co-culture of neutrophil surrogates (HL-60 cells), minimally primed by platelet activating factor (PAF), and resting endothelial cells (EC) results in the elaboration of an hyper-adhesive endothelial surface, as measured by the increase in the expression of endothelial adhes...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.10.018
更新日期:2011-02-01 00:00:00
abstract::The role of specific cytochrome P450 (P450) isoforms in the formation of adducts of 7,12-dimethylbenz(a)anthracene metabolites and membrane proteins has been investigated in vitro with microsomal fractions prepared from rats pretreated with various isoenzyme selective inducers. The effects of isoenzyme selective inhib...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90421-z
更新日期:1991-09-27 00:00:00
abstract::Mechanical stress is known to activate signaling cascades, including mitogen-activated protein kinase (MAPK) pathways. Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanica...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.07.019
更新日期:2005-12-05 00:00:00
abstract::Resveratrol, a natural phytoalexin that shows health-promoting benefits, is an inhibitor of store-operated calcium entry (SOCE). Knowledge of the molecular mechanism underlying this inhibition is required for the proper design of therapies that include resveratrol or related stilbenoids, but remains largely unknown. T...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.09.018
更新日期:2013-12-01 00:00:00
abstract::The ex vivo sensitivity of murine pluripotent hematopoietic stem cells (CFU-S) and myeloid progenitor cells (CFU-GM) to 4-hydroperoxycyclophosphamide, ASTA Z 7557, phosphoramide mustard, acrolein, melphalan, and cis-platinum was determined in the absence and presence of known (disulfiram, diethyldithiocarbamate, cyana...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90719-1
更新日期:1985-10-01 00:00:00
abstract::The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3-me...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90127-9
更新日期:1986-05-01 00:00:00
abstract::Blocking spermidine and spermine synthesis in Plasmodium falciparum-infected erythrocytes with irreversible inhibitors of S-adenosylmethionine decarboxylase (AdoMet DC; EC 4.1.1.50), prevented the growth of the parasite in vitro. The most potent of these compounds, MDL 73811, inhibited growth of chloroquine-sensitive ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90174-4
更新日期:1991-06-01 00:00:00
abstract::MCF-7 human breast cancer cell homogenates and subcellular organelles were submitted to isopycnic centrifugation on Percoll gradients to investigate the subcellular localization of triphenylethylene antiestrogen specific binding sites (AEBS). Electron microscopy revealed that gradient fractions coincident with the mig...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90677-5
更新日期:1986-11-01 00:00:00
abstract::A method to evaluate interactions between biologically active agents is presented. Synergism, zero interaction, and antagonism were easily detected with the three-dimensional approach proposed herein. This method is compatible with a checkerboard design to diagnose the interaction between agents and obviate the need t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(95)02230-9
更新日期:1996-03-08 00:00:00
abstract::Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.09.004
更新日期:2006-12-15 00:00:00
abstract::The identification of proliferation/survival pathways constitutively activated by genetic alterations in multiple myeloma (MM), or sustained by the bone marrow (BM) microenvironment, provides novel opportunities for the development of targeted therapies. The deregulated function of protein tyrosine kinases plays a cri...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.06.023
更新日期:2009-11-01 00:00:00
abstract::Agents that inhibit hepatic cholesterol biosynthesis reduce circulating cholesterol levels in experimental animals and humans, and may be of pharmacological importance in the prevention of atherosclerosis. Azalanstat (RS-21607), a synthetic imidazole, has been shown to inhibit cholesterol synthesis in HepG2 cells, hum...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00152-p
更新日期:1995-08-08 00:00:00
abstract::The effect of deferoxamine on nucleotide metabolism in HL-60 leukemic cells was studied to explore the mechanism of its antiproliferation activity. It was found that in intact cells deferoxamine markedly inhibited the ribonucleotide reduction and incorporation of bases (adenine, hypoxanthine), ribonucleosides (inosine...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90601-0
更新日期:1987-07-15 00:00:00
abstract::The binding of nimodipine, a 1,4-dihydropyridine Ca2+ channel antagonist, and of Bay K 8644, a Ca2+ channel activator, was measured in several regions of rat brain and compared to the distribution of K+ depolarization-induced 45Ca2+ uptake into synaptosomes. The maximum binding densities (Bmax) of [3H]nimodipine and [...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90575-2
更新日期:1987-12-01 00:00:00
abstract::The transcription factor NF-kappaB plays a key role in a wide variety of cellular processes such as innate and adaptive immunity, cellular proliferation, apoptosis and development. In unstimulated cells, NF-kappaB is sequestered in the cytoplasm through its tight association with inhibitory proteins called IkappaBs, c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.06.017
更新日期:2006-10-30 00:00:00
abstract::Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary betwe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.07.024
更新日期:2018-09-01 00:00:00
abstract::In vitro absorption of three angiotensin converting enzyme (ACE) inhibitors, captopril, enalapril and lisinopril, and their stabilities in aqueous buffer as well as their resistance to intestinal and dermal tissue homogenates were investigated. The results demonstrate that the spontaneous oxidation of captopril, enala...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90382-4
更新日期:1994-03-29 00:00:00
abstract::Adiponectin blocks hepatocellular carcinoma (HCC) progression by inducing cell apoptosis through the modulation of C-Jun N-terminal kinase and mammalian target of rapamycin. However, the precise upstream signaling pathways or molecules remain elusive. In the present study, we analyzed the role of antioxidant protein t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.12.001
更新日期:2015-01-15 00:00:00
abstract::Tirapazamine (SR 4233) is a bioreductive antitumour drug in Phase III clinical trial which is activated in hypoxic tumour regions to generate a cytotoxic species. Electron paramagnetic resonance (EPR) spectrometry was used to investigate directly the formation of free radicals as the result of tirapazamine reduction b...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00487-1
更新日期:2000-12-15 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::Glimepiride and glibenclamide act apparently in a closely comparable manner upon both insulin and glucagon release. Except for the decreased efficiency of D-glucose in suppressing glucagon release after a prior exposure of the pancreas to the hypoglycemic sulfonylureas, no evidence was obtained to suggest that a posit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90435-8
更新日期:1991-09-27 00:00:00