Abstract:
:E7070 is a novel sulfonamide anticancer agent that arrests the G(1)/S phase of the cell cycle. Preclinical and phase I studies have demonstrated non-linear pharmacokinetics (PK) of the drug. A population PK analysis revealed that the human plasma concentration-time data were best described by a three-compartment model with non-linear distribution. We have studied the in vitro interaction of 14C-radiolabeled E7070 with red blood cells (RBC) and its binding to plasma proteins in the concentration range where non-linearity in disposition was observed in humans to get more insight into the behavior of the drug. After the addition of E7070 to whole blood at 37 degrees C, the drug is taken up or binds to RBC in a concentration-dependent manner. The addition of sodium azide, however, did not result in a decrease of drug uptake by RBC, indicating passive diffusion processes. A non-linear increase in drug uptake was observed at incubation concentrations above 4 microg/ml E7070 in whole blood. This non-linearity was confirmed by lower partition coefficients between RBC and plasma at higher incubation concentrations (from 2.37 at 4 microg/ml to 0.31 at 200 microg/ml). The plasma protein binding of E7070 was high (98-99%) and linear in the concentration range studied (20-200 microg/ml). In conclusion, E7070 in whole blood is preferentially bound to RBC and exhibits high plasma protein binding. The non-linear distribution of E7070 in humans can be caused, in part at least, by saturable binding of E7070 to RBC.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Bongard HJ,Pluim D,Waardenburg RC,Ravic M,Beijnen JH,Schellens JHdoi
10.1097/00001813-200307000-00003subject
Has Abstractpub_date
2003-07-01 00:00:00pages
405-10issue
6eissn
0959-4973issn
1473-5741journal_volume
14pub_type
杂志文章abstract::In a retrospective study, we calculated the treatment and follow-up costs of patients with newly diagnosed multiple myeloma. The total treatment programme consisted of eight phases: VAD or VAMP chemotherapy, follow-up I, high-dose melphalan followed by transplantation of whole blood, follow-up II, collection of periph...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199811000-00008
更新日期:1998-11-01 00:00:00
abstract::The effects of vitamin C on the oxidative stress in blood platelets induced by cisplatin were studied. In the presence of vitamin C we measured in blood platelets the production of thiobarbituric acid reactive substances (TBARS), the generation of superoxide radicals (O2*-), other reactive oxygen species (H2O2, single...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200007000-00010
更新日期:2000-07-01 00:00:00
abstract::Substitutions in thiophene structure give rise to new derivatives with different biological and pharmacological activities. The present study investigated the cytotoxicity activity of some thiophene derivatives in breast cancer cells maintained in two-dimensional (2D) or in three-dimensional (3D) culture and evaluated...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000581
更新日期:2018-02-01 00:00:00
abstract::Taxotere (RP 56976, NSC 628503) is a new semisynthetic analog of taxol (NSC 125973) with promising antitumor activity in a variety of preclinical screening systems. Clinical responses after treatment with taxol have been observed in ovarian cancer, breast, lung cancer and melanoma. Both agents act through induction of...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199204000-00008
更新日期:1992-04-01 00:00:00
abstract::The aim of this paper was to investigate whether sinoporphyrin sodium (DVDMS) could be a novel sonosensitizer in sonodynamic therapy. We used two kinds of leukemia cells (K562, U937) as main tumor cell models and cells (peripheral blood mononuclear cells, spleen lymphocytes) separated from healthy ICR mice as normal c...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000031
更新日期:2014-02-01 00:00:00
abstract::Vinblastine at doses ranging from 0.2 to 6 mg/kg body weight was administered i.p. to mice in the absence or presence of the drugs PSC 833, cyclosporin A, mefloquine, quinidine and dipyridamole, all compounds that modulate the multidrug resistance pump and thus increase the accumulation of this cytotoxin in drug-resis...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199601000-00007
更新日期:1996-01-01 00:00:00
abstract::Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and b...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000592
更新日期:2018-04-01 00:00:00
abstract::Paeonol, a major phenolic component of Moutan Cortex, is known to have antitumor effects through an unknown mechanism. In this study, we tried to elucidate the anticancer effects of paeonol on human hepatocellular carcinoma (HCC) cell lines BEL-7404, SMMC-7721, and MHCC97-H in vitro. Using the 3-[4,5-dimethylthiazol-2...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282f7f4eb
更新日期:2008-04-01 00:00:00
abstract::Twelve patients received intrapleural instilments of the cytostatic agent mitoxantrone in a total dosage of 30 mg for locoregional palliative therapy of malignant pleural effusion. Effusion could be stopped for a mean period of 3.2 months in 11 patients. ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199202000-00003
更新日期:1992-02-01 00:00:00
abstract::The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-200501000-00003
更新日期:2005-01-01 00:00:00
abstract::One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer ch...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-199502001-00003
更新日期:1995-02-01 00:00:00
abstract::Caffeic acid phenethyl ester (CAPE) is a major propolis component that possesses a variety of pharmacological properties such as antioxidant and anticancer effects. Herein, we investigated the effectiveness of CAPE on cytotoxicity of clinically used anticancer drugs, doxorubicin (DXR) and cisplatin (CDDP), in parental...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000715
更新日期:2019-03-01 00:00:00
abstract::DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199112000-00003
更新日期:1991-12-01 00:00:00
abstract::Uterine sarcomas are rare tumors constituting 1-3% of all uterine malignancies. These tumors are characterized by aggressive growth and by poor overall prognosis. There is much controversy concerning diagnostic criteria and the great variation in histology, as well as the role of radiotherapy and chemotherapy in the m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199102000-00004
更新日期:1991-02-01 00:00:00
abstract::Imatinib mesylate is a specific inhibitor of the Bcr-Abl protein tyrosine kinase that competes with ATP for its specific binding site in the kinase domain. It has activity against platelet-derived growth factor receptor alpha and beta (PDGFR-alpha and -beta), and c-kit, the receptor for stem cell factor. We have used ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000215062.16308.41
更新日期:2006-07-01 00:00:00
abstract::Bevacizumab has been shown to be effective combined with chemotherapy for first-line treatment of advanced colorectal cancer, but little information is available about its efficacy and safety in patients who may be candidates for surgery at any time during the disease. The case history of a female patient with colorec...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000349778.09614.54
更新日期:2009-04-01 00:00:00
abstract::Mitomycin C (MMC) in combination with infusional 5-fluorouracil (5-FU) is a well-tolerated active combination therapy for advanced gastric cancer. Pegylated liposomal doxorubicin (Caelyx) has been combined with this regimen in a phase I study exhibiting promising activity in patients with upper gastrointestinal tumors...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200504000-00010
更新日期:2005-04-01 00:00:00
abstract::The aim of the present study was to investigate the gene expression of biomarkers associated with the sensitivity to fluoropyrimidine and taxanes in recurrent/advanced breast cancer patients treated with first-line capecitabine chemotherapy. We evaluated the clinicopathological/prognostic significance of thymidylate s...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32834f7ef4
更新日期:2012-06-01 00:00:00
abstract::The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000224444.23953.90
更新日期:2006-08-01 00:00:00
abstract::Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200606000-00007
更新日期:2006-06-01 00:00:00
abstract::We performed a phase II, Southwest Oncology Group (SWOG) clinical trial of recombinant human interleukin-4 (rhuIL-4) in patients with previously treated non-Hodgkin's lymphoma (NHL). We studied 18 eligible patients with low-grade and 21 patients with intermediate- or high-grade NHL. All patients had received prior che...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-200010000-00004
更新日期:2000-10-01 00:00:00
abstract::Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability of tumor cells to metastasize because of their capacity to degrade type IV collagen, the main component of basement membrane, and to their elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)-2,6-dioxo-...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328313e15b
更新日期:2008-11-01 00:00:00
abstract::The plasma pharmacokinetics of a second generation anthracycline derivative, idarubicin (Ida), have been studied in 17 patients with acute myelocytic leukemia (AML) and high risk features. The drug (10 mg/m2) was given in a randomized cross-over design as 3 min and 2 h infusions for three consecutive days. Cytosine ar...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00001813-199701000-00005
更新日期:1997-01-01 00:00:00
abstract::Autophagy is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemotherapy. Recently, chloroquine diphosphate (CQ), a widely used antimalarial drug, has been studied as a potential inhibitor of autophagy. Here, we aimed to investigate the role of CQ in...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328353f8c7
更新日期:2012-08-01 00:00:00
abstract::Temozolomide (TMZ) combination with whole-brain radiotherapy (WBRT) has been tested by many randomized controlled trials in the treatment of brain metastases (BMs) in China and other countries. We performed an up-to-date meta-analysis to determine (i) the log odds ratios (LORs) of objective response (ORR) and adverse ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,meta分析,评审
doi:10.1097/CAD.0000000000000295
更新日期:2016-01-01 00:00:00
abstract::We evaluated the activity and toxicity of two sequences of taxol combined with vinorelbine in disseminated malignant melanoma, metastatic beyond regional lymph nodes. Fifteen previously untreated patients, nine males and six females (median age 56 years), were enlisted between May 1994 and February 1995. Eight patient...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199602000-00003
更新日期:1996-02-01 00:00:00
abstract::Our previous studies have demonstrated the in-vitro and in-vivo targeting of a generation-5 (G5) dendrimer-based multifunctional conjugate, which used folic acid (FA) as the targeting agent and methotrexate (MTX) as the chemotherapeutic drug. For the synthesized G5-FA-MTX nanodevice conjugate to be clinically applicab...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282f28842
更新日期:2008-02-01 00:00:00
abstract::Based on observations of a discrepancy between 'hypersensitivity' reactions to docetaxel (DT) and the clinical features of allergic reactions, we explored the hypothesis that DT-induced acute hypersensitivity reactions (AHRs) have a non-allergic origin. Forty cancer patients receiving DT and 16 patients receiving othe...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000131685.06390.b7
更新日期:2004-07-01 00:00:00
abstract::The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199803000-00012
更新日期:1998-03-01 00:00:00
abstract::To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100-300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified us...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000408
更新日期:2016-10-01 00:00:00