Determination of extracellular methotrexate tissue levels by microdialysis in a rat model.


:We used a microdialysis technique to determine tissue methotrexate (MTX) levels during steady state in a rodent model. Two different approaches were employed to measure the actual extracellular MTX concentrations in muscle, liver, and kidney tissues of anesthetized Wistar rats. With the reduced-perfusion-rate technique, the flow in the microdialysis perfusate was gradually decreased toward zero to permit calculation of zero-flow intercepts. Using the net change technique, microdialysis probes were perfused with different MTX concentrations to allow an assessment of equilibrium drug levels. For these two methods to be used, drug concentrations in the matrix to be analyzed must remain unchanged during the experimental procedure. In the animal model, steady state was attained after 1.5 h and maintained throughout the rest of the experiments by the administration of MTX as continuous infusions through a venous catheter. In vitro and in vivo, both the reduced-perfusion-rate and net change techniques gave reproducible data that permitted the estimation of extracellular drug concentrations in the dialyzed tissue compartments.The data suggest that the level of unbound MTX in the circulation is fairly similar to the extracellular concentrations in the muscle and liver. In the kidney, MTX levels were measured to be 3-8 times higher than those of unbound, circulating MTX, and a considerable discrepancy between the two methods used for estimations was apparent. These results demonstrate that both the net change and reduced-flow microdialysis techniques can produce reproducible and precise data. The results may constitute a basis for determining recoveries and, thus, true extracellular drug levels during in vivo microdialysis of MTX. This may be of importance in delineation of the relationship between tissue MTX levels and outcome in a variety of normally inaccessible compartments during cancer pharmacotherapy.


Ekstrøm PO,Andersen A,Warren DJ,Giercksky KE,Slørdal L




Has Abstract


1996-01-01 00:00:00












  • Brain tumor-targeted delivery and therapy by focused ultrasound introduced doxorubicin-loaded cationic liposomes.

    abstract::Brain tumor lacks effective delivery system for treatment. Focused ultrasound (FUS) can reversibly open BBB without impacts on normal tissues. As a potential drug carrier, cationic liposomes (CLs) have the ability to passively accumulate in tumor tissues for their positive charge. In this study, FUS introduced doxorub...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Lin Q,Mao KL,Tian FR,Yang JJ,Chen PP,Xu J,Fan ZL,Zhao YP,Li WF,Zheng L,Zhao YZ,Lu CT

    更新日期:2016-02-01 00:00:00

  • Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

    abstract:OBJECTIVE:We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. SUBJECTS AND METHODS:The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of th...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Yamada Y,Itoh Y,Aoki S,Nakamura K,Taki T,Naruse K,Tobiume M,Zennami K,Katsuda R,Kato Y,Watanabe M,Nishikawa G,Minami M,Nakahira M,Ukai S,Sawada M,Kitamura A,Honda N

    更新日期:2009-11-01 00:00:00

  • CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone.

    abstract:BACKGROUND:Abiraterone became a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Crucitta S,Del Re M,Paolieri F,Bloise F,Sbrana A,Sammarco E,Mercinelli C,Cucchiara F,Fontanelli L,Galli L,Danesi R

    更新日期:2020-10-01 00:00:00

  • A model for ultrafilterable plasma platinum disposition in patients treated with cisplatin.

    abstract::A model incorporating recent information regarding the specificity of a high-performance liquid chromatographic assay for "active" platinum in plasma ultrafiltrate, and the concept of mobile and fixed metabolites, was developed for cancer patients treated with cisplatin. Model parameters were determined using plasma a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Reece PA,Stafford I,Russell J,Khan M,Gill PG

    更新日期:1987-01-01 00:00:00

  • Relationship between the melanin content of a human melanoma cell line and its radiosensitivity and uptake of pimonidazole.

    abstract::The intra-cellular uptake of the weakly basic radiosensitiser pimonidazole (PIMO) was determined as a function of the pigmentation of Na11+ human melanotic melanoma cells in vitro. Two experimental conditions were considered: exponentially growing cells (Exp.) and plateau-phase cells (PI.). The melanin content of Na11...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: el Gamoussi R,Threadgill MD,Prade M,Stratford IJ,Guichard M

    更新日期:1993-01-01 00:00:00

  • Clinical significance of estrogen receptor beta in breast cancer.

    abstract::Ever since the estrogen receptor (ER) beta was discovered in 1996, we have been trying to determine its value as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. Recent progress in cellular experiments has shown that ERbeta works as counter pa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审


    authors: Saji S,Hirose M,Toi M

    更新日期:2005-11-01 00:00:00

  • Interleukin-1 receptor antagonist attenuates cyclophosphamide-induced mucositis in a murine model.

    abstract:PURPOSE:Cyclophosphamide is a cytotoxic chemotherapy drug that causes severe damages to hematopoietic and gastrointestinal systems. The aim of this study is to evaluate the protective effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on chemotherapy-induced mucositis (CIM) in a murine model of c...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Xiang D,Guo Y,Zhang J,Gao J,Lu H,Zhu S,Wu M,Yu Y,Han W

    更新日期:2011-06-01 00:00:00

  • Population pharmacokinetics and exposure-response assessment of veliparib co-administered with temozolomide in patients with myeloid leukemias.

    abstract:PURPOSE:Veliparib is an oral inhibitor of poly(ADP-ribose) polymerase enzyme. Combination of veliparib and temozolomide was well-tolerated and demonstrated clinical activity in older patients with relapsed or refractory acute myeloid leukemia (AML) or AML arising from pre-existing myeloid malignancies. We aimed to perf...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Singh R,Mehrotra S,Gopalakrishnan M,Gojo I,Karp JE,Greer JM,Chen A,Piekarz R,Kiesel BF,Gobburu J,Rudek MA,Beumer JH,ETCTN-6745 study team.

    更新日期:2019-02-01 00:00:00

  • Single- and multiple-dose disposition kinetics of sunitinib malate, a multitargeted receptor tyrosine kinase inhibitor: comparative plasma kinetics in non-clinical species.

    abstract:PURPOSE:The purpose of these extensive non-clinical studies was to assess pharmacokinetics and dispositional properties of sunitinib and its primary active metabolite (SU12662). METHODS:Sunitinib was administered in single and repeat oral doses in mice, rats, and monkeys. Assessments were made using liquid-chromatogra...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Haznedar JO,Patyna S,Bello CL,Peng GW,Speed W,Yu X,Zhang Q,Sukbuntherng J,Sweeny DJ,Antonian L,Wu EY

    更新日期:2009-09-01 00:00:00

  • Taxol cytotoxicity on human leukemia cell lines is a function of their susceptibility to programmed cell death.

    abstract::Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Gangemi RM,Tiso M,Marchetti C,Severi AB,Fabbi M

    更新日期:1995-01-01 00:00:00

  • Circulating angiogenic growth factor levels in mice bearing human tumors using Luminex Multiplex technology.

    abstract::Tumor angiogenesis is essential for tumor growth and metastasis formation. Luminex methodology was used to measure the levels of four angiogenic cytokines in cell culture medium and in the plasma of mice bearing human tumors. We obtained plasma and conditioned culture medium from 12 different human tumor cell lines. T...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Keyes KA,Mann L,Cox K,Treadway P,Iversen P,Chen YF,Teicher BA

    更新日期:2003-04-01 00:00:00

  • Coadministration of vindesine with high-dose methotrexate therapy increases acute kidney injury via BCRP, MRP2, and OAT1/OAT3.

    abstract:PURPOSE:To investigate whether coadministration of vindesine is a risk factor for acute kidney injury caused by high-dose methotrexate in patients with hematologic malignancies and identify its mechanism. METHODS:A retrospective analysis was conducted on 211 cycles of HD-MTX therapy in 178 patients with hematological ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Huang C,Xia F,Xue L,Liu L,Bian Y,Jin Z,Miao L

    更新日期:2020-02-01 00:00:00

  • Long-term prognosis of surgical patients with hepatocellular carcinoma.

    abstract::We reviewed 139 resected patients with hepatocellular carcinoma at our clinic between 1963 and 1987, and using the 118 cases for the period between 1963 and 1986, we analyzed the prognostic factors that influenced the long-term prognosis by comparing the survival curves. Significant differences in the survival pattern...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kawano N,Ohmori Y,Inoue S,Nagao T,Morioka Y

    更新日期:1989-01-01 00:00:00

  • A phase I study of sunitinib combined with modified FOLFOX6 in patients with advanced solid tumors.

    abstract:PURPOSE:This phase I study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib combined with modified FOLFOX6 (mFOLFOX6). METHODS:Patients with advanced solid malignancies received mFOLFOX6 in 2-week cycles with escalating sunitinib doses (2...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Leong S,Eckhardt SG,Chan E,Messersmith WA,Spratlin J,Camidge DR,Diab S,Khosravan R,Lin X,Chow Maneval E,Lockhart AC

    更新日期:2012-07-01 00:00:00

  • A pharmacodynamic model of Bcr-Abl signalling in chronic myeloid leukaemia.

    abstract::Chronic myeloid leukaemia (CML) is an unusual malignancy in which myeloid progenitor cells are transformed by a single chromosomal translocation where the Bcr domain of chromosome 22 is placed adjacent to the proto-oncogene c-Abl of chromosome 9, resulting in constitutive Abl tyrosine kinase activity. This has a twofo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Jackson RC,Radivoyevitch T

    更新日期:2014-10-01 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


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

    更新日期:1984-01-01 00:00:00

  • In vivo antitumor activity by 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone in a solid human carcinoma xenograft model.

    abstract::Previously, we showed that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), isolated from the buds of Cleistocalyx operculatus, significantly inhibited the growth of human liver cancer SMMC-7721 cells and could induce SMMC-7721 cells apoptosis in vitro. Here, we report the antitumor effects of DMC in vivo, usi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ye CL,Liu JW,Wei DZ,Lu YH,Qian F

    更新日期:2005-05-01 00:00:00

  • 5-Fluorouracil's cytotoxicity is enhanced both in vitro and in vivo by concomitant treatment with hyperthermia and dipyridamole.

    abstract::We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Maehara Y,Sakaguchi Y,Takahashi I,Yoshida M,Kusumoto H,Masuda H,Sugimachi K

    更新日期:1992-01-01 00:00:00

  • Hydroxyurea and hydroxamic acid derivatives as antitumor drugs.

    abstract::Hydroxyurea has been used for decades and it is still valuable for the treatment of some types of cancer. It inhibits ribonucleotide reductase (RNR) enzyme known to be crucial in the conversion of ribonucleotides into deoxyribonucleotides. However, nowadays the main focus has shifted to structurally similar hydroxamic...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审


    authors: Saban N,Bujak M

    更新日期:2009-07-01 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


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

    更新日期:2015-05-01 00:00:00

  • Phase I study of a chloroquine-gemcitabine combination in patients with metastatic or unresectable pancreatic cancer.

    abstract:PURPOSE:Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer. METHODS:In...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Samaras P,Tusup M,Nguyen-Kim TDL,Seifert B,Bachmann H,von Moos R,Knuth A,Pascolo S

    更新日期:2017-11-01 00:00:00

  • Phase I study of larotaxel administered as a 1-h intravenous infusion every 3 weeks to Japanese patients with advanced solid tumours.

    abstract::Larotaxel (XRP9881, RPR109881), a novel semi-synthetic taxoid that shares a mode of action with the taxanes docetaxel and paclitaxel, was active in preclinical studies against a broad spectrum of tumour cells and tumour models refractory/resistant to taxanes, and have demonstrated clinical activity in taxane pre-treat...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Yamamoto N,Boku N,Minami H

    更新日期:2009-12-01 00:00:00

  • A Phase Ib multicenter, dose-escalation study of the polyamine analogue PG-11047 in combination with gemcitabine, docetaxel, bevacizumab, erlotinib, cisplatin, 5-fluorouracil, or sunitinib in patients with advanced solid tumors or lymphoma.

    abstract:PURPOSE:Polyamines are absolutely essential for maintaining tumor cell proliferation. PG-11047, a polyamine analogue, is a nonfunctional competitor of the natural polyamine spermine that has demonstrated anticancer activity in cells and animal models of multiple cancer types. Preclinical investigations into the effects...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Murray Stewart T,Von Hoff D,Fitzgerald M,Marton LJ,Becerra CHR,Boyd TE,Conkling PR,Garbo LE,Jotte RM,Richards DA,Smith DA,Stephenson JJ Jr,Vogelzang NJ,Wu HH,Casero RA Jr

    更新日期:2021-01-01 00:00:00

  • Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab.

    abstract:BACKGROUND:The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab. PATIENTS AND METHODS:A retrospective review was performed on 16 consecutive patient...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Nomura M,Otsuka A,Yoshimura M,Nonomura Y,Kaku Y,Matsumoto S,Muto M

    更新日期:2018-05-01 00:00:00

  • Phase II study of weekly docetaxel combined with cisplatin in patients with advanced non-small-cell lung cancer.

    abstract:PURPOSE:To evaluate the safety and efficacy of the combination of cisplatin on day 1 and docetaxel on days 1, 8 and 15 every 4 weeks for the treatment of previously untreated patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:A group of 38 patients with advanced or metastatic NSCLC who had not rece...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Tsunoda T,Koizumi T,Hayasaka M,Hirai K,Koyama S,Takabayashi Y,Fujimoto K,Kubo K

    更新日期:2004-08-01 00:00:00

  • Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the proliferation of three prostate cancer cell lines.

    abstract:PURPOSE:Polyamines are biologic cations necessary for normal cell growth. Polyamine analogues have been shown to be effective inhibitors of tumor growth. We tested the effect of the polyamine analogues 1,1 9-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,15-bis(ethy...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Jeffers L,Church D,Basu H,Marton L,Wilding G

    更新日期:1997-01-01 00:00:00

  • A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).

    abstract:PURPOSE:This study aimed to evaluate the maximum tolerated dose (MTD) and recommended phase II dose (RPTD), as well as the safety and tolerability of PF-03446962, a monoclonal antibody targeting activin receptor like kinase 1 (ALK-1), in combination with regorafenib in patients with refractory metastatic colorectal can...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Clarke JM,Blobe GC,Strickler JH,Uronis HE,Zafar SY,Morse M,Dropkin E,Howard L,O'Neill M,Rushing CN,Niedzwiecki D,Watson H,Bolch E,Arrowood C,Liu Y,Nixon AB,Hurwitz HI

    更新日期:2019-10-01 00:00:00

  • A phase II study of fenretinide in patients with hormone refractory prostate cancer: a trial of the Cancer Therapeutics Research Group.

    abstract:PURPOSE:Fenretinide is a synthetic retinoid with activity in prostate cancer and other cell lines. The aim of this study was to assess the efficacy and tolerability of fenretinide in chemotherapy-naïve men with hormone refractory prostate cancer. METHODS:Eligibility criteria included hormone refractory prostate cancer...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Moore MM,Stockler M,Lim R,Mok TS,Millward M,Boyer MJ

    更新日期:2010-10-01 00:00:00

  • The stability of mesna in beverages and syrup for oral administration.

    abstract::We evaluated the stability of the aqueous formulation of mesna during storage in syringes and after dilution in beverages and syrups. Measurements of the concentrations of mesna showed that the undiluted formulation was stable for at least 9 days in standard polypropylene syringes at 5 degrees, 24 degrees, and 35 degr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Goren MP,Lyman BA,Li JT

    更新日期:1991-01-01 00:00:00

  • Inhibition of human breast cancer colony formation by anticalmodulin agents: trifluoperazine, W-7, and W-13.

    abstract::The effects of anticalmodulin agents, namely trifluoperazine (TFP) and two naphthalene sulfonamide derivatives (W-7 and W-13), were tested on the growth of a human breast cancer cell line (MDA-MB-231) using a soft agar clonogenic assay. The results of this in vitro study reveal that TFP, W-7, and W-13 had the ability ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Wei JW,Hickie RA,Klaassen DJ

    更新日期:1983-01-01 00:00:00