Kinetic parameters for reversal of the multidrug pump as measured for drug accumulation and cell killing.


:We determined the kinetic parameters that describe the effect of 20 different modulators of the multidrug resistance pump on the reversal of cytotoxin accumulation in a resistant strain of P388 leukemia cells (P388/ADR), and on the reversal of cell killing for these cells. When measured by a direct comparison of the amplitude of the pertinent protocol (accumulation or cell killing), the Ki for reversal of accumulation was generally some four or five times larger than that for reduction of cytotoxicity. We showed that this was only an apparent discrepancy, since a full theoretical analysis of the two protocols allowed the intrinsic Ki to be obtained for the two procedures and these computed Ki values were then almost identical. We found that for six of the modulators studied (namely, cyclosporin A, quinidine, dipyridamole, propafenone, mefloquine, tamoxifen) the extent of pump reversal should be better than 90% at tolerated plasma levels culled from the literature.


Lan LB,Ayesh S,Lyubimov E,Pashinsky I,Stein WD




Has Abstract


1996-01-01 00:00:00












  • Phase II study of hepatic artery infusion with 5-fluorouracil, adriamycin, and mitomycin C (FAM) in liver metastases from colorectal carcinoma.

    abstract::Twenty-seven patients with liver metastases from colorectal carcinoma were treated with 5-fluorouracil, adriamycin, and mitomycin C (FAM) by hepatic artery infusion (HAI) every 2-3 months for a maximum of eight courses. Median survival for all patients was 22 months. Toxicity was acceptable and consisted in severe mye...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Wils J,Schlangen J,Naus A

    更新日期:1984-01-01 00:00:00

  • cis-Diamminedichloroplatinum(II)-induced cell death through apoptosis in sensitive and resistant human ovarian carcinoma cell lines.

    abstract::We have studied the effects of the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-platin) on three human ovarian carcinoma cell lines - one sensitive to the drug (CH1), one with acquired resistance (CH1cisR) and one with intrinsic resistance (SKOV-3). Previous work has shown that the 50% inhibitory concen...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ormerod MG,O'Neill C,Robertson D,Kelland LR,Harrap KR

    更新日期:1996-01-01 00:00:00

  • Potentiation of etoposide-induced cytotoxicity and DNA damage in CCRF-CEM cells by pretreatment with non-cytotoxic concentrations of arabinosyl cytosine.

    abstract::Pretreatment of the human lymphoblastoid cell line CCRF-CEM with 0.02 microM arabinosyl cytosine (ara C) enhances both the cytotoxic and the DNA-damaging effects of etoposide. This concentration of ara C is itself non-cytotoxic and results in no detectable DNA damage as measured by alkaline elution. Ara C pretreatment...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Chresta CM,Hicks R,Hartley JA,Souhami RL

    更新日期:1992-01-01 00:00:00

  • Effects of elotuzumab on QT interval and cardiac safety in patients with multiple myeloma.

    abstract:PURPOSE:To assess the effect of elotuzumab on corrected QT (QTc) intervals and cardiac safety. METHODS:Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (tre...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Passey C,Darbenzio R,Jou YM,Lynch M,Gupta M

    更新日期:2016-12-01 00:00:00

  • Antitumor activity of interleukin 12 in preclinical models.

    abstract::Interleukin 12 (IL-12) is a heterodimeric cytokine with a number of biological effects that are consistent with its potential role as an antitumor agent. The antimetastatic and antitumor activities of IL-12 have been demonstrated in a number of murine tumor models. Both the inhibition of established experimental pulmo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审


    authors: Brunda MJ,Luistro L,Rumennik L,Wright RB,Dvorozniak M,Aglione A,Wigginton JM,Wiltrout RH,Hendrzak JA,Palleroni AV

    更新日期:1996-01-01 00:00:00

  • The role of methoxymorpholino anthracycline and cyanomorpholino anthracycline in a sensitive small-cell lung-cancer cell line and its multidrug-resistant but P-glycoprotein-negative and cisplatin-resistant counterparts.

    abstract::The cytotoxic action of two morpholino anthracyclines, methoxymorpholino anthracycline (MRA-MT, FCE 23,762) and cyanomorpholino anthracycline (MRA-CN), was compared with the cytotoxicity of doxorubicin (DOX), the topoisomerase II inhibitor etoposide (VP-16), the topoisomerase I inhibitor camptothecin, methotrexate, an...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: van der Graaf WT,Mulder NH,Meijer C,de Vries EG

    更新日期:1995-01-01 00:00:00

  • The development of targeted chemotherapy for CNS lymphoma-a pilot study of the IDARAM regimen.

    abstract:PURPOSE:We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination. PATIENTS AND METHODS:In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM wh...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Moreton P,Morgan GJ,Gilson D,Smith GM,McVerry BA,Davies JM,Mackie MJ,Bolam S,Jalihal SS,Howard MR,Parapia LA,Williams AT,Child JA,Central and Southern Lymphoma Group.

    更新日期:2004-04-01 00:00:00

  • 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


    authors: Song J,Melera PW

    更新日期:2001-11-01 00:00:00

  • Comparison of the anticancer effect of ADMOS alone and ADMOS with CDDP in the treatment of hepatocellular carcinoma by intra-arterial injection.

    abstract::A total of 135 patients with hepatocellular carcinoma (HCC) were treated by intra-arterial injection of an Adriamycin/mitomycin C oil (lipiodol) suspension (ADMOS) alone or of ADMOS plus cis-diammine-dichloroplatinum (CDDP). In all, 59 patients were treated with ADMOS alone and 76 were treated with ADMOS plus CDDP. A ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Ikeda K,Inoue H,Yano T,Kobayashi H,Nakajo M

    更新日期:1992-01-01 00:00:00

  • Low dose--high dose: what is the right dose? Pharmacokinetic modeling of etoposide.

    abstract:PURPOSE:Some clinical studies on etoposide (Eto) have shown marked schedule dependency of the effect (starting at about 1 mg/l) and toxicity (over about 10 mg/l) whereas other studies have not confirmed these results. What are the conclusions we can draw from these inconsistent results when developing new low-dose (LD)...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Würthwein G,Boos J

    更新日期:2002-04-01 00:00:00

  • Etoposide sensitivity of radioresistant human glioma cell lines.

    abstract:PURPOSE:Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Beauchesne P,Bertrand S,N'guyen MJ,Christianson T,Dore JF,Mornex F,Bonner JA

    更新日期:1998-01-01 00:00:00

  • Dosing sequence-dependent pharmacokinetic interaction of oxaliplatin with paclitaxel in the rat.

    abstract:BACKGROUND:In a phase I clinical trial of oxaliplatin (OPT) in combination with paclitaxel (PXL), a pharmacokinetic interaction was observed when OPT was given as a 2-h i.v. infusion followed by a 1-h i.v. infusion of PXL. The purpose of this study was to use a rat model to evaluate whether the pharmacokinetic interact...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Liu J,Kraut EH,Balcerzak S,Grever M,D'Ambrosio S,Chan KK

    更新日期:2002-12-01 00:00:00

  • Extraction of tamoxifen and its metabolites from formalin-fixed, paraffin-embedded tissues: an innovative quantitation method using liquid chromatography and tandem mass spectrometry.

    abstract:PURPOSE:Tamoxifen is a key therapeutic option for breast cancer treatment. Understanding its complex metabolism and pharmacokinetics is important for dose optimization. We examined the possibility of utilizing archival formalin-fixed paraffin-embedded (FFPE) tissue as an alternative sample source for quantification sin...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ng ES,Kangarloo SB,Konno M,Paterson A,Magliocco AM

    更新日期:2014-03-01 00:00:00

  • Serum microRNA-21 predicted treatment outcome and survival in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab.

    abstract:PURPOSE:The purpose of this study was to evaluate the expression of ser-miRNAs at different periods during treatment and analyze their relationship with therapeutic response and prognosis in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab (NCCT). METHODS:Venous blood w...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Liu B,Su F,Lv X,Zhang W,Shang X,Zhang Y,Zhang J

    更新日期:2019-11-01 00:00:00

  • Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines.

    abstract:PURPOSE:Arsenic compounds have been found to be effective in the treatment of acute promyelocytic leukemia through the downregulation of bcl-2 expression. Resistant ovarian cancer cells often overexpress bcl-2 or p53 proteins or both. We hypothesized that arsenic compounds, such as As2O3 and As2S3, could also be active...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Du YH,Ho PC

    更新日期:2001-06-01 00:00:00

  • Etoposide (VP16-213) and teniposide (VM26) comparative in vitro activities in human tumors.

    abstract::In order to determine if any inherent sensitivity differences may exist between VP16-213 and VM26 individual human tumors were grown in vitro and drug sensitivities were determined using the soft agar clonogenic assay method. Only nine of the 34 tumors tested so far showed a differing sensitivity to VP16-213 and VM26 ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Issell BF,Tihon C,Curry ME

    更新日期:1982-01-01 00:00:00

  • Comparison of uptake of mitomycin C and KW-2149 by murine P388 leukemia cells sensitive or resistant to mitomycin C.

    abstract::KW-2149, a new mitomycin C (MMC) derivative, inhibited the growth of murine P388 leukemia in vitro at 20-fold lower concentrations than those of MMC. KW-2149 was also effective in inhibiting the growth of MMC-resistant P388 (P388/MMC) cells. To elucidate these characteristics of KW-2149, its uptake and efflux were com...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kobayashi E,Okabe M,Kono M,Arai H,Kasai M,Gomi K,Lee JH,Inaba M,Tsuruo T

    更新日期:1993-01-01 00:00:00

  • Inhibition of growth factor binding, Ca2+ signaling and cell growth by polysulfonated azo dyes related to the antitumor agent suramin.

    abstract::The ability of the polysulfonated antitumor drug suramin and six related polysulfonated azo dyes to inhibit the cell growth, platelet-derived growth factor (PDGF)-receptor binding, and intracellular Ca2+ signaling of Swiss 3T3 fibroblasts was studied. Some of the azo dyes were more potent inhibitors of PDGF binding th...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Powis G,Seewald MJ,Melder D,Hoke M,Gratas C,Christensen TA,Chapman DE

    更新日期:1992-01-01 00:00:00

  • Multicenter phase II study of combination therapy with cetuximab and S-1 in patients with KRAS exon 2 wild-type unresectable colorectal cancer previously treated with irinotecan, oxaliplatin, and fluoropyrimidines (KSCC 0901 study).

    abstract:PURPOSE:Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Takahashi T,Emi Y,Oki E,Kobayashi K,Tsuji A,Shimokawa M,Tanaka T,Akagi Y,Ogata Y,Baba H,Yoshida K,Natsugoe S,Maehara Y,Kyushu Study Group of Clinical Cancer (KSCC).

    更新日期:2016-09-01 00:00:00

  • Phase I-II study of the somatostatin analogue lanreotide in hormone-refractory prostate cancer.

    abstract::Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin grow...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Maulard C,Richaud P,Droz JP,Jessueld D,Dufour-Esquerré F,Housset M

    更新日期:1995-01-01 00:00:00

  • Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer.

    abstract::Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phas...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Rosenblum MG,Hortobagyi GN

    更新日期:1986-01-01 00:00:00

  • Oral bioavailability of docetaxel in combination with OC144-093 (ONT-093).

    abstract:OBJECTIVE:Docetaxel given orally as monotherapy results in low bioavailability of <10%. Previous studies have indicated that the intestinal efflux pump P-glycoprotein (P-gp) prevents uptake from the gut resulting in low systemic exposure to docetaxel. The purpose of this study was to determine the degree of enhancement...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Kuppens IE,Bosch TM,van Maanen MJ,Rosing H,Fitzpatrick A,Beijnen JH,Schellens JH

    更新日期:2005-01-01 00:00:00

  • Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine.

    abstract:PURPOSE:Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has cancer chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Marczylo TH,Verschoyle RD,Cooke DN,Morazzoni P,Steward WP,Gescher AJ

    更新日期:2007-07-01 00:00:00

  • Epirubicin: a phase II study in recurrent small-cell lung cancer.

    abstract::Epirubicin (4'-epidoxorubicin), an analogue of doxorubicin (Adriamycin), has established activity in the treatment of small-cell lung cancer (SCLC) when used at doses of 75 to 120 mg/m2 in previously untreated patients. We completed a phase II study of epirubicin (85 mg/m2 given intravenously at 3-week intervals) in 2...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Rosenthal M,Kefford R,Raghavan D,Stuart-Harris R

    更新日期:1991-01-01 00:00:00

  • Positive relationship between subsequent chemotherapy and overall survival in pancreatic cancer: meta-analysis of postprogression survival for first-line chemotherapy.

    abstract:PURPOSE:To gain a better understanding of the impact of postprogression survival (PPS) and post-trial anticancer therapy on overall survival (OS) in first-line pancreatic cancer patients. METHODS:A literature search identified 54 randomized trials, focusing on gemcitabine monotherapy to eliminate effects of heterogene...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,meta分析,评审


    authors: Kasuga A,Hamamoto Y,Takeuchi A,Kawasaki K,Suzuki T,Hirata K,Sukawa Y,Takaishi H,Kanai T

    更新日期:2017-03-01 00:00:00

  • Pegylated liposomal doxorubicin in combination with vinorelbine as salvage treatment in pretreated patients with advanced breast cancer: a multicentre phase II study.

    abstract:PURPOSE:To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. PATIENTS AND TREATMENT:Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Ardavanis A,Mavroudis D,Kalbakis K,Malamos N,Syrigos K,Vamvakas L,Kotsakis A,Kentepozidis N,Kouroussis C,Agelaki S,Georgoulias V,Breast Cancer Committee of the Hellenic Oncology Research Group.

    更新日期:2006-12-01 00:00:00

  • Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

    abstract:PURPOSE:Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excis...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kelner MJ,McMorris TC,Rojas RJ,Estes LA,Suthipinijtham P

    更新日期:2008-12-01 00:00:00

  • The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse.

    abstract::The pharmacokinetics of pentamethylmelamine (PMM) have been investigated in mouse (Balb C-, CBA/LAC, nude), rat (Wistar), and man. In all three species, PMM was extensively demethylated to N2,N2,N4,N6-tetramethylmelamine and N2,N4,N6-trimethylmelamine, although marked species differences in the rate of metabolism were...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Rutty CJ,Newell DR,Muindi JR,Harrap KR

    更新日期:1982-01-01 00:00:00

  • Effects of bevacizumab on plasma concentration of irinotecan and its metabolites in advanced colorectal cancer patients receiving FOLFIRI with bevacizumab as second-line chemotherapy.

    abstract:PURPOSE:Bevacizumab (BV) prolongs the survival of colorectal cancer patients when combined with irinotecan (CPT-11)-based regimens. In the AVF2107g study, the area under the curve (AUC) ratio for bolus CPT-11/5-fluorouracil (5-FU)/leucovorin (LV) (IFL) with the BV arm to bolus IFL with placebo indicated that SN-38 conc...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Horita Y,Yamada Y,Hirashima Y,Kato K,Nakajima T,Hamaguchi T,Shimada Y

    更新日期:2010-02-01 00:00:00

  • A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement.

    abstract::Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirub...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Jakobsen P,Bastholt L,Dalmark M,Pfeiffer P,Petersen D,Gjedde SB,Sandberg E,Rose C,Nielsen OS,Mouridsen HT

    更新日期:1991-01-01 00:00:00