In vivo microdialysis to characterize drug transport in brain tumors: analysis of methotrexate uptake in rat glioma-2 (RG-2)-bearing rats.

Abstract:

:Brain microdialysis was applied to sample free methotrexate (MTX) concentrations in brain extracellular fluid of normal and RG-2 glioma-bearing rats. All animals received 50 mg/kg of MTX intra-arterially following which serial blood and interstitial fluid samples were collected for 3 h and measured for MTX by an HPLC assay. Retrodialysis was used to estimate the in vivo recovery of MTX from brain. A linear two-compartment model was fitted to the plasma MTX concentration-time data in both the normal and RG-2 groups. The mean total body clearance and volume of distribution at steady state of MTX varied from 0.90 +/- 0.3 to 0.24 +/- 0.02 l h-1 kg-1 (P < 0.05) and from 0.58 +/- 0.24 to 0.21 +/- 0.16 l kg-1 (P < 0.05) in control and tumor rats, respectively. The significant reductions in clearance and volume of distribution at steady-state were attributed in part to a cachectic state in the RG-2 animals in which total body water was reduced. The mean MTX area under the interstitial fluid concentration-time curve (AUC) was 171.6 +/- 69.14 micrograms min ml-1(control) and 583.5 +/- 296.7 micrograms min ml-1 (brain tumor-bearing rats). The significantly higher AUC values obtained with RG-2 rats compared with control rats may have resulted from high plasma MTX concentrations and a more permeable blood-tumor barrier (BTB). A hybrid physiologically based pharmacokinetic model was used to characterize the mechanisms responsible for the high MTX brain tumor concentrations. In conclusion, a microdialysis technique was successfully utilized to examine the extracellular uptake of MTX in brain. This technique can be a powerful tool to evaluate intracerebral drug kinetics and the delivery of drugs to brain tumors.

authors

Devineni D,Klein-Szanto A,Gallo JM

doi

10.1007/s002800050518

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

499-507

issue

6

eissn

0344-5704

issn

1432-0843

journal_volume

38

pub_type

杂志文章
  • Cancer and the tumor microenvironment: a review of an essential relationship.

    abstract:PURPOSE:The role of the microenvironment during the initiation and progression of carcinogenesis is now realized to be of critical importance, both for enhanced understanding of fundamental cancer biology, as well as exploiting this source of relatively new knowledge for improved molecular diagnostics and therapeutics....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-008-0881-9

    authors: Mbeunkui F,Johann DJ Jr

    更新日期:2009-03-01 00:00:00

  • Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients.

    abstract::Cyclophosphamide pharmacokinetics have been studied in 16 female patients with advanced breast cancer. The group included 7 patients who were greater than 20%, less than or equal to 30% over ideal body weight and 5 patients who were greater than 30% over ideal body weight. Cyclophosphamide plasma elimination half-live...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00570489

    authors: Powis G,Reece P,Ahmann DL,Ingle JN

    更新日期:1987-01-01 00:00:00

  • ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein.

    abstract:PURPOSE:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective cytotoxicity to transformed cells. However, most human hepatocellular carcinomas (HCC) develop resistance to TRAIL. Thus, there is an urgent need to investigate the molecular targets and the unde...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-011-1763-0

    authors: Wang G,Zhan Y,Wang H,Li W

    更新日期:2012-03-01 00:00:00

  • Renal function in the elimination of oral melphalan in patients with multiple myeloma.

    abstract::Pharmacokinetic studies in 11 patients with multiple myeloma were undertaken on the first and last days of one course of chemotherapy. The drug was administered PO in single doses of 6-14 mg daily. Melphalan concentrations were determined by high-performance liquid chromatography. The interpatient variability of pharm...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00306752

    authors: Adair CG,Bridges JM,Desai ZR

    更新日期:1986-01-01 00:00:00

  • Phase I and pharmacokinetic study of mitomycin C and celecoxib as potential modulators of tumor resistance to irinotecan in patients with solid malignancies.

    abstract:PURPOSE:Based on the preclinical evidence of topoisomerase I (Topo-1) upregulation by mitomycin C(MMC) and decreased NF-kappaB activation by celecoxib, we evaluated combinations of irinotecan/MMC and irinotecan/MMC/celecoxib in patients with advanced solid malignancies. PATIENTS-METHODS:Initially, patients received MM...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0826-3

    authors: Xu Y,Kolesar JM,Schaaf LJ,Drengler R,Duan W,Otterson G,Shapiro C,Kuhn J,Villalona-Calero MA

    更新日期:2009-05-01 00:00:00

  • Combination therapy with docetaxel and low dose of cisplatin in elderly patients with advanced non-small cell lung cancer: multicenter phase II study.

    abstract:PURPOSE:To determine the efficacy and safety of the combination therapy with docetaxel and cisplatin (CDDP) at low doses in elderly patients with advanced NSCLC. PATIENTS AND METHODS:A total of 42 patients aged > or =70 years with previously untreated advanced NSCLC received docetaxel 75 mg/m(2) plus CDDP 50 mg/m(2) o...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-008-0749-z

    authors: Feliu J,Firvida JL,Castro J,Madroñal C,Rodríguez-Jaráiz A,Salgado M,Belda-Iniesta C,Casado E,García-Mata J,González-Barón M,Oncopaz Cooperative Group.

    更新日期:2009-02-01 00:00:00

  • Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET.

    abstract:PURPOSE:This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS:To test the hypothesis that MGMT deficiency was required for an al...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-018-3700-y

    authors: Hijioka S,Sakuma K,Aoki M,Mizuno N,Kuwahara T,Okuno N,Hara K,Yatabe Y

    更新日期:2019-01-01 00:00:00

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

    abstract::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 a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050468

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

    更新日期:1996-01-01 00:00:00

  • Biweekly docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy for advanced esophageal squamous cell carcinoma: a phase I dose-escalation study.

    abstract:BACKGROUND AND PURPOSE:The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinom...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1447-1

    authors: Tanaka Y,Yoshida K,Sanada Y,Osada S,Yamaguchi K,Takahashi T

    更新日期:2010-11-01 00:00:00

  • Distribution of radioactivity and anthracycline-fluorescence in tissues of mice one hour after [14C]-labeled AD 32 administration. Evidence for tissue aglycone formation.

    abstract::Levels of radioactivity and total anthracycline fluorescence in tissues of A/JAX mice were compared 1 h after IV administration of unlabeled or [14C]-labeled AD 32 (50 mg/kg). Highest levels of both fluorescence and radioactivity were found in the small intestine (including contents) and liver, a result consistent wit...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00253006

    authors: Israel M,Karkowsky AM,Khetarpal VK

    更新日期:1981-01-01 00:00:00

  • High-dose VP16 cisplatinum in soft tissue sarcoma of children.

    abstract::Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with initial metastatic disease, (one patient, partial response, one patient), refractory primary, (two patients, relapse, five patients) were treated with a combination of high-dose VP16 (100 mg/m2 daily for 5 days) and cisplatin (40 mg/m2 daily ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685912

    authors: Grabois M,Frappaz D,Bouffet E,Carrie C,Bouhour D,Philip T,Brunat-Mentigny M

    更新日期:1994-01-01 00:00:00

  • Impact of capecitabine and S-1 on anticoagulant activity of warfarin in patients with gastrointestinal cancer.

    abstract:PURPOSE:Capecitabine and S-1 are orally administered fluoropyrimidine anticancer drugs widely used to treat gastrointestinal cancer. While anticoagulant therapy for cancer patients is recommended, many studies have shown that the effects of warfarin are enhanced by its interaction with fluoropyrimidine. We investigated...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-3080-0

    authors: Hata T,Kudo T,Sakai D,Takahashi H,Haraguchi N,Nishimura J,Hata T,Mizushima T,Yamamoto H,Doki Y,Mori M,Satoh T

    更新日期:2016-08-01 00:00:00

  • R-etodolac (SDX-101) and the related indole-pyran analogues SDX-308 and SDX-309 potentiate the antileukemic activity of standard cytotoxic agents in primary chronic lymphocytic leukaemia cells.

    abstract:OBJECTIVE:SDX-101 is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac, and has anti-tumour activity in chronic lymphocytic leukaemia (CLL). SDX-308 and SDX-309 are more potent, structurally related indole-pyran analogues of SDX-101. The current study was performed to i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0400-9

    authors: Lindhagen E,Nissle S,Leoni L,Elliott G,Chao Q,Larsson R,Aleskog A

    更新日期:2007-09-01 00:00:00

  • Effect of cyclosporine A on the tissue distribution and pharmacokinetics of etoposide.

    abstract:PURPOSE:Cyclosporine A (CyA) is able to inhibit P-glycoprotein (P-gp) and to increase cytotoxicity of some anticancer drugs, including etoposide. However, the effect of CyA on the distribution of etoposide in normal tissues, which could affect their toxicity, has not been studied extensively. The purpose of this study ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-004-0784-3

    authors: Cárcel-Trullols J,Torres-Molina F,Araico A,Saadeddin A,Peris JE

    更新日期:2004-08-01 00:00:00

  • Plasma and cerebrospinal fluid pharmacokinetics of 9-aminocamptothecin (9-AC), irinotecan (CPT-11), and SN-38 in nonhuman primates.

    abstract:PURPOSE:The plasma and cerebrospinal fluid (CSF) pharmacokinetics of the camptothecin analogs, 9-aminocamptothecin (9-AC) and irinotecan, were studied in a nonhuman primate model to determine their CSF penetration. METHODS:9-AC, 0.2 mg/kg (4 mg/m2) or 0.5 mg/kg (10 mg/m2), was infused intravenously over 15 min and iri...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050768

    authors: Blaney SM,Takimoto C,Murry DJ,Kuttesch N,McCully C,Cole DE,Godwin K,Balis FM

    更新日期:1998-01-01 00:00:00

  • Effect of axitinib on the QT interval in healthy volunteers.

    abstract:PURPOSE:Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1-3, approved for second-line treatment of advanced renal cell carcinoma (RCC). Preclinical studies did not indicate potential for axitinib-induced delayed cardiac repolarization. METHODS:The effect of axitinib on corr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00280-015-2677-z

    authors: Ruiz-Garcia A,Houk BE,Pithavala YK,Toh M,Sarapa N,Tortorici MA

    更新日期:2015-03-01 00:00:00

  • A phase I trial of topotecan plus tivantinib in patients with advanced solid tumors.

    abstract:PURPOSE:Tyrosine kinase inhibitors (TKI) that target MET signaling have shown promise in various types of cancer, including lung cancer. Combination strategies have been proposed and developed to increase their therapeutic index. Based on preclinical synergy between inhibition of MET and topoisomerase I, a phase I stud...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-018-3672-y

    authors: Liu SV,Groshen SG,Kelly K,Reckamp KL,Belani C,Synold TW,Goldkorn A,Gitlitz BJ,Cristea MC,Gong IY,Semrad TJ,Xu Y,Xu T,Koczywas M,Gandara DR,Newman EM

    更新日期:2018-10-01 00:00:00

  • Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy.

    abstract:PURPOSE:This study was designed to evaluate the anti-tumor activity and toxicity profile of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma (NPC) who had been pretreated with platinum-based chemotherapy. METHOD:This is an open label, single arm phase II trial. All patients were treated ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-007-0441-8

    authors: Zhang L,Zhang Y,Huang PY,Xu F,Peng PJ,Guan ZZ

    更新日期:2008-01-01 00:00:00

  • Combination of three cytotoxic agents in small-cell lung cancer.

    abstract:PURPOSE:The established treatment for small-cell lung cancer has been a cisplatin-etoposide combination, as the most effective chemotherapy regimen. Paclitaxel has also been used in combination with cisplatin and etoposide but this has been unacceptable due to the toxicity. This toxicity could be attributed to the thre...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-012-2022-8

    authors: Stathopoulos GP,Trafalis D,Dimitroulis J,Kosmas Ch,Stathopoulos J,Tsavdaridis D

    更新日期:2013-02-01 00:00:00

  • The relative toxicity of intravenous and intraperitoneal doses of epirubicin.

    abstract::The toxicity of single doses of the anthracycline epirubicin was compared in the rat after either the intravenous (i.v.; 2-6 mg/kg) or intraperitoneal (i.p.; 4-8 mg/kg) administration of the drug. These doses produced comparable acute toxicity that was characterised by a dose-dependent, transient reduction in body wei...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00257620

    authors: Yeung TK,Simmonds RH,Hopewell JW

    更新日期:1989-01-01 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

    doi:10.1007/s00280-016-3182-8

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

    更新日期:2016-12-01 00:00:00

  • Pharmacokinetic studies of 9-nitrocamptothecin on intermittent and continuous schedules of administration in patients with solid tumors.

    abstract:PURPOSE:Oral administration of 9-nitrocamptothecin (9NC), and the formation of its metabolite 9-aminocamptothecin (9AC), may be associated with high interpatient and intrapatient variability. Therefore, we evaluated the plasma pharmacokinetics and urine recovery of 9NC administered on three different schedules as part ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-004-0835-9

    authors: Jung LL,Ramanathan RK,Egorin MJ,Jin R,Belani CP,Potter DM,Strychor S,Trump DL,Walko C,Fakih M,Zamboni WC

    更新日期:2004-12-01 00:00:00

  • Increased anticoagulant activity of warfarin used in combination with doxifluridine.

    abstract:PURPOSE:The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. METHODS:International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased af...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1249-5

    authors: Nakajima M,Genda T,Suehira M,Satoh H,Miki A,Hori S,Sawada Y

    更新日期:2010-10-01 00:00:00

  • Mechanisms of resistance to 6-thioguanine in a murine pancreatic tumor.

    abstract::PANC02 is a unique experimental animal tumor that fails to respond significantly to any known clinically active antitumor agent. In this regard, the murine ductal adenocarcinoma resembles its human counterpart. To study the mechanism for its intrinsic resistance to 6-thioguanine (TG), we compared the metabolism of the...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00684850

    authors: Pan BF,Priebe TS,Nelson JA

    更新日期:1992-01-01 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

  • Synergistic interaction between tetrandrine and chemotherapeutic agents and influence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines.

    abstract:PURPOSE:Tetrandrine (Tet), a bis-benzylisoquinoline alkaloid that was isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known as processing a marked antitumor effect in vitro and in vivo. The aim of this study was to assess the interaction between tetrandrine and chemotherapeutic age...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-007-0416-9

    authors: Wei J,Liu B,Wang L,Qian X,Ding Y,Yu L

    更新日期:2007-10-01 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

    doi:10.1007/BF00685514

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

    更新日期:1991-01-01 00:00:00

  • Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.

    abstract:PURPOSE:Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine k...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-014-2668-5

    authors: Merchan JR,Qin R,Pitot H,Picus J,Liu G,Fitch T,Maples WJ,Flynn PJ,Fruth BF,Erlichman C

    更新日期:2015-03-01 00:00:00

  • The role of preoperative intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation for bladder cancer.

    abstract::Twenty patients with bladder cancer (T1, 3 patients; T2, 6 patients; T3, 8 patients; T4a, 3 patients) were preoperatively treated with intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation. The originally scheduled operations were as follows: total cystectomy in 16 patients (T1 + cis, 1 pati...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00262477

    authors: Uyama T,Moriwaki S,Yokozeki A,Kitada K,Higa I,Shiotsu T,Fujita J

    更新日期:1987-01-01 00:00:00

  • Comparison of the potency of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factors in neutropenic and nonneutropenic CD rats.

    abstract::Recent studies in human bone-marrow culture and healthy human volunteers suggest that lenograstim [glycosylated, recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Chinese hamster ovary (CHO) cells] has greater in vivo potency than filgrastim [nonglycosylated, methionine-extended recombinan...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050570

    authors: Nohynek GJ,Plard JP,Wells MY,Zerial A,Roquet F

    更新日期:1997-01-01 00:00:00