BCNU-induced quantitative and qualitative changes in hepatic cytochrome P-450 can be correlated with cholestasis.

Abstract:

:Male Sprague-Dawley rats were given single i.p. injections of 1,3-bis(2-chloroethyl)-1-Nitrosourea (BCNU) to investigate changes in hepatic microsomal cytochrome P-450 content and metabolic activity. On day 14 after treatment (20 mg/kg), cytochrome P-450 content had decreased by approximately 25% and ethylmorphine N-demethylase activity (nmol product/nmol P-450/min) had decreased by 36%. In contrast, ethylmorphine O-deethylase and 7-ethoxycoumarin O-deethylase activities were not significantly decreased by BCNU treatment. Hepatic delta-aminolevulinic acid synthetase activity was only 60% of control values, and microsomal heme oxygenase activity was slightly but not statistically elevated. Cytochrome P-450 content in control and BCNU-treated rats increased in a similar manner after phenobarbital or beta-naphthoflavone induction. Electrophoretic analysis of cytochrome P-450 proteins isolated from hepatic endoplasmic reticular membranes of treated and control rats suggested that alterations in these proteins occurred in BCNU-treated rats. These changes in cytochrome P-450 content and activity are very similar to those reported in isolated systems exposed to bile acids or in rats with experimentally produced cholestasis. BCNU has been shown to produce cholestasis, which precedes its effects on microsomal mixed-function oxygenase activity. Thus, the delayed effects of BCNU on microsomal drug metabolism are probably secondary to its interference with bile formation.

authors

Stolzenbach JC,Larson RE

doi

10.1007/BF00684877

subject

Has Abstract

pub_date

1990-01-01 00:00:00

pages

227-35

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

25

pub_type

杂志文章
  • Further characterization of the sixth transmembrane domain of Pgp1 by site-directed mutagenesis.

    abstract:PURPOSE:Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side coul...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800100354

    authors: Song J,Melera PW

    更新日期:2001-11-01 00:00:00

  • Effect of cyclosporine on colchicine partitioning in the rat liver.

    abstract::Colchicine is secreted into bile as a major pathway of elimination. Cyclosporine (CsA) inhibits colchicine biliary secretion. In the present study, the effects of cyclosporine and its vehicle (cremophor) on the partitioning of colchicine across the liver were studied. CsA decreased the colchicine bile/plasma ratio fro...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685886

    authors: Speeg KV,Maldonado AL

    更新日期:1993-01-01 00:00:00

  • Translational research of a novel humanized epidermal growth factor receptor-related protein: a putative inhibitor of pan-ErbB.

    abstract:PURPOSE:The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-011-1748-z

    authors: Fu XH,Li J,Huang JJ,Zheng S,Zhang SZ

    更新日期:2011-12-01 00:00:00

  • Randomized crossover antiemetic study in cisplatin-treated patients. Comparison between high-dose i.v. metoclopramide and high-dose i.v. dexamethasone.

    abstract::This prospective, randomized, nonblind study comparing the antiemetic effectiveness of high-dose IV metoclopramide and high-dose IV dexamethasone was performed in 78 advanced cancer patients. Chemotherapeutic treatment consisted in cisplatin at a high-dose (120 mg/m2) (HD-CDDP) and at a low-dose (LD-CDDP), either alon...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00299870

    authors: Frustaci S,Grattoni E,Tumolo S,Crivellari D,Figoli F,Galligioni E,Veronesi A,Tirelli U,Grigoletto E

    更新日期:1986-01-01 00:00:00

  • Mass balance, pharmacokinetics, and metabolism of linsitinib in cancer patients.

    abstract:PURPOSE:This study characterized the pharmacokinetics, mass balance, routes and extent of elimination, metabolites, and safety of a single oral dose of (14)C-linsitinib, an IGF-1R/IR inhibitor, in patients with advanced solid tumors. The tolerability of linsitinib after multiple-dose administration was assessed in thos...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-2999-5

    authors: Poondru S,Chaves J,Yuen G,Parker B,Conklin E,Singh M,Nagata M,Gill S

    更新日期:2016-04-01 00:00:00

  • Phase II study of docetaxel, capecitabine, and cisplatin as neoadjuvant chemotherapy for locally advanced breast cancer.

    abstract:PURPOSE:Docetaxel, capecitabine, and cisplatin are effective chemotherapeutic agents for breast cancer with significant synergistic cytotoxicity demonstrated by in vitro studies. The purpose of this study was to assess the efficacy of a combination of docetaxel, capecitabine, and cisplatin (TXP) in patients diagnosed w...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-010-1401-2

    authors: Lu YS,Chen DR,Tseng LM,Yeh DC,Chen ST,Hsieh CM,Wang HC,Yeh HT,Kuo SH,Huang CS

    更新日期:2011-06-01 00:00:00

  • Minimization of inflammation in the treatment of bladder tumors by intravesical instillation of adriamycin.

    abstract::The purpose of this trial was to minimize local inflammation caused by intravesical instillation of antitumor agents, especially Adriamycin, in the treatment of bladder tumor. Tranexamic acid was chosen as the solvent vehicle for Adriamycin and IV bolus injection of an antiallergic drug, Stronger neo-minophagen C, was...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00256726

    authors: Ohi Y,Okamoto K,Kawabata T,Hanafusa A,Fai CY,Kakinoki T,Kawahara M,Asechi S,Sakamoto N,Nagata S

    更新日期:1983-01-01 00:00:00

  • Acquired resistance to O6-benzylguanine plus chloroethylnitrosoureas in human breast cancer.

    abstract:PURPOSE:O(6)-benzylguanine (BG) is a pseudosubstrate inactivator of the DNA repair protein O(6)- alkylguanine-DNA alkyltransferase (AGT) that has entered clinical trials as a potentiator of the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). This study was designed to evaluate potential mechanisms of B...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050984

    authors: Phillips WP Jr,Gerson SL

    更新日期:1999-01-01 00:00:00

  • A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors.

    abstract:PURPOSE:This phase I trial was initiated to evaluate the safety, pharmacokinetics (PK) and maximum tolerated dose (MTD) of the glycolytic inhibitor, 2-deoxy-D-glucose (2DG) in combination with docetaxel, in patients with advanced solid tumors. METHODS:A modified accelerated titration design was used. 2DG was administe...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-012-2045-1

    authors: Raez LE,Papadopoulos K,Ricart AD,Chiorean EG,Dipaola RS,Stein MN,Rocha Lima CM,Schlesselman JJ,Tolba K,Langmuir VK,Kroll S,Jung DT,Kurtoglu M,Rosenblatt J,Lampidis TJ

    更新日期:2013-02-01 00:00:00

  • Population pharmacokinetics of bevacizumab in cancer patients with external validation.

    abstract:BACKGROUND:Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics. METHODS:Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-3079-6

    authors: Han K,Peyret T,Marchand M,Quartino A,Gosselin NH,Girish S,Allison DE,Jin J

    更新日期:2016-08-01 00:00:00

  • LLL-3, a STAT3 inhibitor, represses BCR-ABL-positive cell proliferation, activates apoptosis and improves the effects of Imatinib mesylate.

    abstract:PURPOSE:The chimeric protein BCR-ABL, a constitutively active protein-tyrosine kinase, triggers downstream signalling proteins, such as STAT3, ultimately resulting in the survival of myeloid progenitors in BCR-ABL-positive leukemias. Here, we evaluated the effect of LLL-3, an inhibitor of STAT3 activity, on cell viabil...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-009-1109-3

    authors: Mencalha AL,Du Rocher B,Salles D,Binato R,Abdelhay E

    更新日期:2010-05-01 00:00:00

  • New folate analogs of the 10-deaza-aminopterin series. Further evidence for markedly increased antitumor efficacy compared with methotrexate in ascitic and solid murine tumor models.

    abstract::A group of folate analogs of the 10-deaza-aminopterin series, which were designed on the basis of the results of an intensive biochemical and pharmacokinetic program, have been examined in therapy experiments utilizing a group of murine tumor models. These new analogs were found to be markedly superior to methotrexate...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:

    authors: Sirotnak FM,DeGraw JI,Schmid FA,Goutas LJ,Moccio DM

    更新日期:1984-01-01 00:00:00

  • Phase I and pharmacokinetic study of weekly NV06 (Phenoxodiol), a novel isoflav-3-ene, in patients with advanced cancer.

    abstract:BACKGROUND:We wished to define the maximum tolerated dose (MTD), toxicity, and pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a compound with a diphenolic structure related chemically and biologically to genistein and flavopiridol. PATIENTS AND METHODS:Twenty-one patients with advanced canc...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0189-6

    authors: de Souza PL,Liauw W,Links M,Pirabhahar S,Kelly G,Howes LG

    更新日期:2006-10-01 00:00:00

  • Angiotensin-(1-7) synergizes with colony-stimulating factors in hematopoietic recovery.

    abstract:PURPOSE:Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and t...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-013-2312-9

    authors: Rodgers KE,Espinoza TB,Roda N,Meeks CJ,diZerega GS

    更新日期:2013-12-01 00:00:00

  • Autophagy in cancer stem/progenitor cells.

    abstract::Macroautophagy is widely accepted as a cytoprotective mechanism against various environmental stresses. While inhibition of autophagy is generally considered to increase the susceptibility of cancer cells to therapeutic agents, whether it also plays a similar role in tumor stem cells is unclear and still controversial...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-014-2634-2

    authors: Lin YH,Huang YC,Chen LH,Chu PM

    更新日期:2015-05-01 00:00:00

  • The role of deoxycytidine-metabolizing enzymes in the cytotoxicity induced by 3'-amino-2',3'-dideoxycytidine and cytosine arabinoside.

    abstract::The cellular metabolism of 3'-amino-2',3'-dideoxycytidine (3'-NH2-dCyd), a cytotoxic agent previously reported to be a poor substrate for purified Cyd/dCyd deaminase (dCydD), was compared with that of cytosine arabinoside (ara-C) in cells that displayed dCydD activity (HeLa) and in cells that did not (L1210). Growth i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686406

    authors: Mancini WR

    更新日期:1992-01-01 00:00:00

  • The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel.

    abstract::The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-005-1013-4

    authors: Agata N,Nogi H,Bamberg M,Milhollen M,Pu M,Weitman S,Kharbanda S,Kufe D

    更新日期:2005-12-01 00:00:00

  • Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    abstract:PURPOSE:Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, l...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-013-2176-z

    authors: Patel KJ,Trédan O,Tannock IF

    更新日期:2013-07-01 00:00:00

  • Sandostatin desensitization--a strategy useful for patients with carcinoid tumors, intolerant to sandostatin.

    abstract::Sandostatin immediate release (IR) is frequently used to treat patients with carcinoid tumors. However, some patients are unable to tolerate the immediate side effects of sandostatin IR leading to discontinuation of the drug. There is no literature available to guide the management of patients' sensitivity/intolerance...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1436-4

    authors: Vinjamaram S,Iyer R

    更新日期:2011-07-01 00:00:00

  • Cellular pharmacology of 1-beta-D-arabinofuranosylcytosine in human myeloid, B-lymphoid and T-lymphoid leukemic cells.

    abstract::The in vitro inhibitory action and metabolism of 1-beta-D-arabinofuranosylcytosine (ara-C) on human myeloid (HL-60), B-lymphoid (RPMI-8392), and T-lymphoid (Molt-3) leukemic cells was compared. Ara-C produced greater inhibitory effects in Molt-3 cells than in either HL-60 or RPMI-8392 cells. At a 48 h exposure, ara-C ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00689099

    authors: Momparler RL,Onetto-Pothier N,Bouffard DY,Momparler LF

    更新日期:1990-01-01 00:00:00

  • Dependence on PI3K/Akt signaling for malignant rhabdoid tumor cell survival.

    abstract:PURPOSE:Malignant rhabdoid tumors (MRT), although rare, are one of the most aggressive pediatric malignancies. Loss of INI1, a tumor suppressor gene and member of the SWI/SNF chromatin remodeling complex, is a recurrent genetic characteristic of these tumors and an important diagnostic marker. We have previously demons...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0796-5

    authors: Foster K,Wang Y,Zhou D,Wright C

    更新日期:2009-04-01 00:00:00

  • Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin with or without systemic gemcitabine after curative resection for pancreatic adenocarcinoma.

    abstract:BACKGROUND:The role of adjuvant therapy in pancreatic cancer remains controversial. Gemcitabine given systemically seems to be effective; intra-arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS:The goal was to evaluate the impact of postoperative IAC followed or not by systemic gemcitabine in pati...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/s00280-006-0200-2

    authors: Cantore M,Serio G,Pederzoli P,Mambrini A,Iacono C,Pulica C,Capelli P,Lombardi M,Torri T,Pacetti P,Pagani M,Fiorentini G

    更新日期:2006-10-01 00:00:00

  • Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines.

    abstract:PURPOSE:To evaluate in vitro interactions of carboplatin, gemcitabine and paclitaxel in molecularly defined non-small-cell lung cancer lines. MATERIALS AND METHODS:Three NSCLC lines, A549 (p16-,p53 wt, Rb wt), Calu-1 (p16-, p53-, Rb+) and H596 (p16 wt, p53 mut, Rb-) were utilized. Cells were exposed to carboplatin, ge...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800000273

    authors: Edelman MJ,Quam H,Mullins B

    更新日期:2001-08-01 00:00:00

  • Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study.

    abstract::A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02897298

    authors: Whitehead VM,Bernstein ML,Vega R,Vats T,Dyment P,Vietti TJ,Krischer J

    更新日期:1990-01-01 00:00:00

  • Preclinical pharmacology of the antitumor agent O-6-methylguanine in CDF1 mice.

    abstract::O-6-methylguanine (O6-mG), a guanine analog recently shown to be a potent inhibitor of alkylguanine-DNA alkyltransferase, has been found to potentiate the antitumor activity of nitrosoureas, in particular, carmustine (BCNU), in resistant cell lines (HT-29 mer+) and is targeted for development as a modulating agent wit...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686216

    authors: Avramis VI,Chan KK,Solorzano MM,Chen ZL

    更新日期:1993-01-01 00:00:00

  • Angiostatin potentiates cyclophosphamide treatment of metastatic disease.

    abstract:PURPOSE:We examined the interaction between cyclophosphamide (CPA) and angiostatin (AS) on the growth of primary Lewis lung carcinoma (LLC) tumors and on the development of LLC pulmonary metastases. We studied the effects of AS and CPA on the stages of angiogenesis employing in vitro assays. METHODS:Primary tumor grow...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0514-7

    authors: Mauceri HJ,Seetharam S,Beckett MA,Schumm LP,Koons A,Gupta VK,Park JO,Manan A,Lee JY,Montag AG,Kufe DW,Weichselbaum RR

    更新日期:2002-11-01 00:00:00

  • Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.

    abstract:PURPOSE:Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semisynthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducte...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0533-4

    authors: Alvarado Y,Cortes J,Verstovsek S,Thomas D,Faderl S,Estrov Z,Kantarjian H,Giles FJ

    更新日期:2003-01-01 00:00:00

  • Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients.

    abstract:INTRODUCTION:Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to p...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-017-3455-x

    authors: van Andel L,Rosing H,Zhang Z,Hughes L,Kansra V,Sanghvi M,Tibben MM,Gebretensae A,Schellens JHM,Beijnen JH

    更新日期:2018-01-01 00:00:00

  • Marimastat (BB2516): current status of development.

    abstract::Marimastat (BB-2516) is the first matrix metalloproteinase inhibitor to have entered clinical trials in the field of oncology. It has excellent bioavailability and has completed phase I and II trials. Phase I studies involved healthy volunteers who received short courses of marimastat; these were well tolerated. Sympt...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s002800051099

    authors: Steward WP

    更新日期:1999-01-01 00:00:00

  • Reduced cardiotoxicity and increased cytotoxicity in a novel anthracycline analogue, 4'-amino-3'-hydroxy-doxorubicin.

    abstract::The acute and chronic cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4'-amino-3'-hydroxy-DXR were compared with those of 4'-deoxy-DXR and DXR. In the acute cardiotoxicity study, the ECG and hemodynamic changes recorded in anesthetized rats that had been treated i.v. with 10 mg/kg 4'-amino-3'...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685942

    authors: Danesi R,Bernardini N,Agen C,Costa M,Zaccaro L,Pieracci D,Malvaldi G,Del Tacca M

    更新日期:1992-01-01 00:00:00