Abstract:
:We evaluated the combination SN38 (7-ethyl-10-hydroxycamptothecin) -5fluorouracil (5FU) +/- folinic acid (FA) on six human colon cancer cell lines expressing spontaneous sensitivity to both drugs. Tumoral parameters potentially related to drug sensitivity were investigated: topoisomerase I (topo I) cleavable complexes formed with SN38, thymidylate synthase (TS) activity, folylpolyglutamate synthetase activity and dihydropyrimidine dehydrogenase activity. Drugs (SN38 and/or 5FU +/- FA) were applied for 72 hr, either sequentially or together. The concentration ratio between SN38 and 5FU was 100. Cytotoxicity (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] test), DNA flow cytometry and isobologram analysis (Chou and Talatay) were performed. Based on 5FU IC50 values and isobologram analyses, the most cytotoxic schedule was SN38 followed by 5FU - FA, with high synergistic effects. Flow cytometry indicated that SN38 induced a more or less marked S-G2 block in all cell lines. Sensitivity to SN38, 5FU +/- FA, or combinations were not linked to the potential above-cited tumoral parameters. Interestingly, an inverse correlation was demonstrated between TS activity and topo I cleavable complexes (r2 = 0.78, P = 0.019). These data emphasize the critical importance of the irinotecan-5FU schedule and strongly support this association for the treatment of potentially 5FU-sensitive tumors.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Pavillard V,Formento P,Rostagno P,Formento JL,Fischel JL,Francoual M,Etienne MC,Milano Gdoi
10.1016/s0006-2952(98)00205-6subject
Has Abstractpub_date
1998-11-15 00:00:00pages
1315-22issue
10eissn
0006-2952issn
1873-2968pii
S0006-2952(98)00205-6journal_volume
56pub_type
杂志文章abstract::Phenobarbital (PB) and certain structurally-related compounds induce a variety of hepatic drug-metabolizing enzymes in many strains of rats. Thus, following administration of PB (300, 500 ppm), barbital (BB, 1500 ppm) or 5-ethyl-5-phenylhydantoin (EPH, 500 ppm), CYP2B1-mediated benzyloxyresorufin O-dealkylase activity...
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
abstract::L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00110-2
更新日期:2003-05-01 00:00:00
abstract:AIMS:Protein Kinase R (PKR) plays a key role in inflammation and insulin resistance. Cytokines, high fat diet, infection and various stress signals can activate PKR. However, the functional significance of PKR in diabetic cardiomyopathy (DCM) is not explored so far. Thus the aim of the present study was to investigate ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.113948
更新日期:2020-07-01 00:00:00
abstract::The family of natural red pigments, called prodigiosins (PGs), characterised by a common pyrrolylpyrromethene skeleton, are produced by various bacteria. Some members have immunosuppressive properties and apoptotic effects in vitro and they have also displayed antitumour activity in vivo. Understanding the mechanism o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(03)00496-9
更新日期:2003-10-15 00:00:00
abstract::A method for the isolation of an intact, non-covalent complex formed by the interaction of aldose reductase, NADP(H) nucleotide, and inhibitor has been developed to aid in the discovery and development of novel aldose reductase inhibitors. In the complexes isolated, both the carboxylic acid-containing inhibitor tolres...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00332-9
更新日期:2000-02-15 00:00:00
abstract::We tested the ability of a wide variety of organic compounds, including benzene and phenol derivatives, aromatic amines, pyrazoline derivatives and other non-steroidal anti-inflammatory drugs, to act as cosubstrates during the horseradish peroxidase/hydrogen peroxide-mediated oxygenation of arachidonic acid. Structura...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90326-2
更新日期:1989-04-15 00:00:00
abstract::Several hepatotoxic agents with varied chemical mechanisms of toxicity (acetaminophen, diquat, and CCl4) depress membrane calcium pumps and/or enhance the permeability of membranes to calcium. To probe the relevance of these findings to maintenance of calcium homeostasis after toxins in vivo, we measured the activity ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90016-6
更新日期:1989-09-15 00:00:00
abstract::Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased the expression of tissue factor, a membrane-anchored glycoprotein that initiates blood coagulation on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human monocyte/macrophages. On monocyte/macrophages, oleic acid strongly inhibite...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90118-x
更新日期:1994-07-19 00:00:00
abstract::Novel therapies for the treatment of solid tumors have generally failed to improve patient overall survival. These therapeutic approaches are typically focused on targeting signaling pathways implicated in cell growth and/or survival in order to shrink the malignant mass and achieve an objective clinical response; how...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.03.020
更新日期:2009-08-15 00:00:00
abstract::The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfox...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90430-2
更新日期:1986-10-01 00:00:00
abstract::Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90468-c
更新日期:1993-10-05 00:00:00
abstract::HO-1 (heme oxygenase-1), an antioxidant enzyme, induced by rosiglitazone (PPAR ligands) can be a potential treatment of inflammation. However, the mechanisms of rosiglitazone-induced HO-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain largely unknown. In this study, we found that upregulatio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.12.024
更新日期:2018-02-01 00:00:00
abstract::The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the admin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90475-6
更新日期:1983-05-01 00:00:00
abstract::It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2009.07.020
更新日期:2009-12-15 00:00:00
abstract::Human mono- and lymphocytes from peripheral blood and the monoblastoid cell line U-937 were used in this in vitro study of drug-induced lipidosis. Mono- and lymphocytes were exposed for 4 days to three different tricyclic antidepressants (TCAs), imipramine (25 microM), clomipramine (10 microM) and citalopram (80 micro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)82443-4
更新日期:1997-05-15 00:00:00
abstract::Taxol-based chemotherapy is widely used as the first-line treatment for non-small cell lung cancer (NSCLC), however, the subsequent development of taxol-resistance is a major concern and challenge, resulting in tumor relapse and poor prognosis. Given the complex nature of taxol-resistance, we further delved into its m...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.113733
更新日期:2020-01-01 00:00:00
abstract::Sublines of K562 human leukemia cells were selected for resistance (30- to 80-fold) to etoposide by continuous exposure to 0.5 microM VP-16. Two etoposide-resistant cell lines, K/VP.5 and K/VP.5-1, showed a 5-fold reduction in levels of topoisomerase II alpha protein compared with K562 cells. Northern analysis indicat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90643-b
更新日期:1993-12-03 00:00:00
abstract::DNA methylation is a mammalian epigenetic mark that participates to define where and when genes are expressed, both in normal cells and in the context of diseases. Like other epigenetic marks, it is reversible and can be modulated by chemical agents. Because it plays an important role in cancer by silencing certain ge...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2016.12.004
更新日期:2017-04-01 00:00:00
abstract::Aldehyde oxidase (AOX) is a cytosolic enzyme responsible for the metabolism of some drugs and drug candidates. AOX catalyzes the oxidative hydroxylation of substrates including several aliphatic and aromatic aldehydes, and nitrogen-containing heterocyclic compounds. AOX is also reported to catalyze the reductive metab...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.09.002
更新日期:2017-12-01 00:00:00
abstract::The major metabolic products of the endogeneous catecholamine dopamine are its 3- and 4-O-sulphates which have also been implicated as intermediates in noradrenaline biosynthesis. Because of the unsatisfactory status of the literature concerning the synthesis, isolation, purity and characterisation of the dopamine O-s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90115-0
更新日期:1982-07-01 00:00:00
abstract::The metabolism of tienilic acid, a drug containing a thiophene ring, was reinvestigated in man, rat and dog. The major urinary metabolite in man and rat was isolated and completely characterized by comparison with a synthetic compound. This metabolite derives from the hydroxylation of the thiophene ring of tienilic ac...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90409-x
更新日期:1984-05-01 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::SR 4233 or WIN 59075 (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a novel and highly selective hypoxic cell cytotoxin requiring reductive bioactivation for its impressive antitumour effects. Expression of appropriate reductases will contribute to therapeutic selectivity. Here we provide more detailed information on th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90007-6
更新日期:1992-07-22 00:00:00
abstract::Nucleoside diphosphokinase (NDK) of human platelets has been purified by chromatography on Blue Sepharose CL-6B gel (purification factor of 950) and shown to be free of adenylate kinase, ATPase and adenylate cyclase. The molecular weight was 70,000 with subunits of 17,000. The pH optimum was 8.0 Km values for ATP and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90762-8
更新日期:1986-12-15 00:00:00
abstract::Improved syntheses, based on Lewis acid-catalyzed nucleosidation, are described for the preparation of 5-alkyl-2'-deoxyuridines. These were converted to their 5'-phosphates with the use of wheat shoot phosphotransferase. The dUMP analogues, 5-ethyl-dUMP and 5-propyl-dUMP, were competitive vs dUMP inhibitors of thymidy...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90683-x
更新日期:1984-09-01 00:00:00
abstract::Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine ch...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.06.001
更新日期:2015-08-01 00:00:00
abstract::A process of differentiation was observed when ob17 preadipocyte cells were stably transfected with a vector containing the cDNA of the human A1 adenosine receptor of adipose tissue. Growth of the cell lines continued but was slowed relative to untransfected cells and cells transfected with vector alone, never attaini...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00069-6
更新日期:1999-07-01 00:00:00
abstract::The 5-HT1A receptor is a critical mediator of serotonergic (5-HT) function. We have identified 13 potential single nucleotide polymorphisms resulting in amino acid changes throughout the human 5-HT1A receptor. The pharmacological profiles of these 13 polymorphic variants were then characterized using a high-throughput...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.09.030
更新日期:2004-02-01 00:00:00
abstract::Mitochondrial carriers are proteins that shuttle a variety of metabolites, nucleotides and coenzymes across the inner mitochondrial membrane. The mitochondrial ADP/ATP carriers (AACs) specifically translocate the ATP synthesized within mitochondria to the cytosol in exchange for the cytosolic ADP, playing a key role i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.11.019
更新日期:2016-01-15 00:00:00
abstract::Studies have shown that CYP2C9.1 mediated metabolism of flurbiprofen or naproxen is activated by co-incubation with dapsone. However, dapsone activation has not been examined in the known variant forms of CYP2C9. Six concentrations of flurbiprofen (2-300microM) or naproxen (10-1800 microM) were co-incubated with six c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.01.017
更新日期:2004-05-15 00:00:00