Abstract:
:Verapamil, cyclosporin A (CsA), the cyclosporin derivative SDZ PSC 833 and the novel cyclopeptolide SDZ 280-446 were tested for their capacity to chemosensitize a P-glycoprotein (Pgp)-expressing multi-drug resistant (MDR) variant of the CEM human T lymphoblastoid cell subline (CCRF ACTD 400+). That MDR-CEM cell subline had been previously selected for MDR by actinomycin D and displayed a very high resistance phenotype: 3700-fold for actinomycin D, 3900-fold for vincristine, 1200-fold for taxol, 1000-fold for daunomycin (DAU) and 400-fold for colchicine. Interestingly, these MDR-CEM cells displayed little chemosensitization by resistance-modulating agents (RMA) which presumably work by inhibiting Pgp function. These MDR-CEM cells displayed virtually no chemosensitization by 1 microM verapamil or 1 microgram/ml (about 0.8 microM) CsA, whereas their chemosensitization for different anti-cancer drugs (ACD) was rather stable (from 51- to 82-fold) with 1 microgram/ml (about 0.8 microM) SDZ 280-446, while being very unbalanced (from 5- to 38-fold) with 1 microgram/ml (about 0.8 microM) SDZ PSC 833. Exposure of the MDR-CEM cells to Pgp-directed RMAs, during their loading with DAU (DAU-loading phase), hardly restored DAU retention: SDZ 280-446 being as poorly active as SDZ PSC 833, and about only 3- and 4-fold more active than CsA and verapamil. In contrast, SDZ PSC 833 treatment of human MDR-KB and MDR-LoVo cell lines under the same conditions could restore most or all the DAU retention shown by the parental (Par) cells, in spite of their high level of resistance. By keeping the MDR-CEM cells in the presence of RMA throughout the experiment (both DAU-loading and DAU-efflux phases), a better DAU retention could be restored by the different RMAs used, their order of relative restoration activity being SDZ 280-446 3- to 4-fold > SDZ PSC 833 3- to 10-fold > CsA 2- to 4-fold > verapamil. Nevertheless, the level of DAU retention restored in the MDR-CEM cells reached a plateau at 50% of the Par-CEM cell level. Therefore, although the MDR-CEM cells expressed easily detectable membranous Pgp molecules and probably used them for DAU efflux, they displayed an additional efflux mechanism that was not sensitive to the Pgp inhibitors.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Jachez B,Loor Fsubject
Has Abstractpub_date
1993-12-01 00:00:00pages
605-15issue
6eissn
0959-4973issn
1473-5741journal_volume
4pub_type
杂志文章abstract::We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32801265eb
更新日期:2007-04-01 00:00:00
abstract::The aim of this study was to evaluate whether radiolabeled iodoerythronitroimidazole (IETNIM) could predict the radiosensitization effect on tumors. Tumor-bearing mice were irradiated at a dose of 25, 31 and 37 Gy after the injection of IETNIM. They were also exposed to 37 Gy radiation at 35, 70, 140 and 240 min after...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199611000-00007
更新日期:1996-11-01 00:00:00
abstract::RNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328013c04f
更新日期:2007-04-01 00:00:00
abstract::Rats received an intraperitoneal bolus injection of etoposide at 5 mg/kg of body weight in the form of an etoposide microcrystal suspension in oil (ETOP-OIL) or an aqueous etoposide solution. The tissue distribution was subsequently analyzed using high performance liquid chromatography. ETOP-OIL delivered significantl...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199302000-00003
更新日期:1993-02-01 00:00:00
abstract::Cryptophycin (CP)-52, a synthetic analog of CP-1, possesses potent and selective antiproliferative activity against human solid tumors both and. Based on an algorithm developed in this laboratory using HCT-116 human colon adenocarcinoma cells, CP-52 exhibited a time- and concentration-dependent antiproliferative effec...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200211000-00010
更新日期:2002-11-01 00:00:00
abstract::The sap of Euphorbia peplus, commonly know as 'petty spurge', 'radium weed' or 'milkweed' has been used for centuries as a traditional treatment for skin conditions, including warts, corns and cancers of the skin. Documentation of its use by medical professionals to treat basal cell carcinoma (BCC) dates from the earl...
journal_title:Anti-cancer drugs
pub_type:
doi:10.1097/CAD.0b013e3280149ec5
更新日期:2007-03-01 00:00:00
abstract::Thrombin is a potent mitogen for many tumor cells, suggesting that this enzyme may be involved in tumor genesis and metastasis. Inhibition of thrombin expressed on the surface of tumor cells may improve outcomes in some tumor cases. For this reason, a thrombin inhibitor to be applied in antitumor therapy must have fav...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200402000-00007
更新日期:2004-02-01 00:00:00
abstract::Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recent...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000508
更新日期:2017-08-01 00:00:00
abstract::Our objective was to clarify the efficacy of UFT administration after the complete resection of non-small cell lung cancer (NSCLC) at a single-center institution, avoiding the biases produced by interinstitutional differences. A total of 30 patients who underwent the complete resection of NSCLC at our hospital between...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00001813-200401000-00005
更新日期:2004-01-01 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::Since 5-fluorouracil (5-FU) was synthesized in the late 1950s it has become an important component of many anticancer treatment regimens. The increasing volume of literature accumulating about this drug is evidence that the optimal administration schedule and its combination with modulators has yet to be determined. M...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199406000-00002
更新日期:1994-06-01 00:00:00
abstract::To investigate whether mammalian DNA topoisomerase II is directly involved in recombination events, the effects of ICRF-193, a specific catalytic inhibitor on sister chromatid exchange (SCE), were examined in MR-6 cells. ICRF-193 only slightly elevated SCE formation after 3 or 44 h treatments, while VP-16, a cleavable...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199707000-00013
更新日期:1997-07-01 00:00:00
abstract::Cabozantinib capsules (COMETRIQ) are approved for the treatment of patients with progressive metastatic medullary thyroid cancer. Cabozantinib tablets are investigational drug products considered to be potentially preferred pharmaceutical dosing forms. Two phase I open-label single-dose studies in healthy individuals ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,随机对照试验
doi:10.1097/CAD.0000000000000366
更新日期:2016-08-01 00:00:00
abstract::Taxol is an antitumor drug which, as its mechanism of action, promotes microtubule assembly in vitro. Camptothecin (CPT) is an anticancer agent with the peculiar mechanism of poisoning eukaryotic DNA topoisomerase I. Both drugs are in clinical trials and their chemotherapeutic efficacy seems promising in refractory hu...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199607000-00007
更新日期:1996-07-01 00:00:00
abstract::Previous in vitro biochemical studies have revealed that the antitumor drug leinamycin causes oxidative DNA damage and DNA alkylation. However, it is still not clear whether the same mechanism(s) of action operate in cultured human tumor cells. Here, we evaluated the effects of leinamycin in the human pancreatic carci...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000136886.72917.6f
更新日期:2004-08-01 00:00:00
abstract::The role of pazopanib in the second-line setting of refractory metastatic transitional cell carcinoma of the urothelium has not been defined clearly. The aim of this phase I/II trial was to assess the safety, tolerability, and efficacy of combining pazopanib and vinflunine in patients with metastatic transitional cell...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835efe78
更新日期:2013-04-01 00:00:00
abstract::We investigated whether Ukrain modulates the malignant phenotype of clear cell renal cell carcinoma (ccRCC) cells Caki-1, Caki-2, and ACHN treated with four doses (5, 10, 20, and 40 μmol/l) for 24 and 48 h. The epithelial-to-mesenchymal transition markers E-cadherin, β-catenin, and vimentin were analyzed by immunofluo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328346c7f7
更新日期:2011-09-01 00:00:00
abstract::The beta-carboline alkaloids are naturally existing plant substances. It is known that these alkaloids have a wide spectrum of neuropharmacological, psychopharmacological, and antitumor effects. Therefore, they have been traditionally used in oriental medicine for the treatment of various diseases including cancers an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32832a2dd9
更新日期:2009-06-01 00:00:00
abstract::Glassy cell carcinoma (GCC) of the uterine cervix is a highly malignant tumor and has a poor prognosis. As yet, no effective systemic chemotherapy to this tumor has been reported. Here we describe a case of recurrent GCC that responded to paclitaxel and carboplatin combination treatment. The patient, a 32-year-old wom...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200108000-00010
更新日期:2001-08-01 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::Clinical empiricism has recognized resistant breast cancer as a privileged target for docetaxel (Taxotere). This worldwide registration will offer medical oncologists the opportunity to develop new indications for docetaxel. Pharmacokinetics, preclinical optimal combination and clinical practice will constitute the ra...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:1996-08-01 00:00:00
abstract::Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown their efficacy in metastatic colorectal cancer. The synergism of these drugs has been demonstrated in vivo and in vitro. The aim of this study was to determine the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/01.cad.0000127146.50172.8a
更新日期:2004-06-01 00:00:00
abstract::Schlafen-11 (SLFN11) showed a highly significant positive correlation with the response of topoisomerase inhibitors in cancer cell lines derived from prostate, lung, etc. However, this finding has not been validated in colorectal cancers (CRCs). Although irinotecan (CPT-11), a topoisomerase inhibitor, is one of the mo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000151
更新日期:2014-11-01 00:00:00
abstract::Imexon is an investigational anti-cancer agent, pharmaceutically formulated as a lyophilized solid for i.v. infusion requiring reconstitution and subsequent dilution in infusion fluid before infusion. Imexon contains a highly reactive aziridine ring in its structure, which limits its stability in aqueous solutions. In...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000172833.70444.ba
更新日期:2005-08-01 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::The goal of our study was to determine whether an apoptosis assay used after short-term drug exposure could predict selective toxicity to cancer cells. To this end we compared the effect of eight anticancer drugs and 10 toxic compounds without known antitumor activity in cultures of human breast cancer cells and norma...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200308000-00008
更新日期:2003-08-01 00:00:00
abstract::We have investigated the pharmacokinetics of nevirapine and paclitaxel in a patient who used both drugs concomitantly, as there are strong theoretical indications for a potential pharmacokinetic drug-drug interaction. Plasma concentrations of nevirapine (dose: 200 mg twice daily orally) and paclitaxel (dose: 100 mg/m(...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200507000-00006
更新日期:2005-07-01 00:00:00
abstract::1,4-Anthraquinone (AQ) was synthesized and shown to prevent L1210 leukemic cells from synthesizing macromolecules and growing in vitro. In contrast, its dihydroxy-9,10anthraquinone precursor, quinizarin, was inactive. The antitumor activity of AQ was compared to that of daunorubicin (DAU), which is structurally differ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200006000-00004
更新日期:2000-06-01 00:00:00
abstract::A lack of cross-resistance between the aromatase inhibitors (AIs) provides evidence to suggest that there are clinical differences between these agents. Available data from clinical trials indicate that patients exposed to nonsteroidal AIs may benefit from a steroidal compound of similar biochemical potency, and durab...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/01.cad.0000277875.81122.25
更新日期:2008-03-01 00:00:00
abstract::The effects of 1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol (EDL-155) on the growth of glioma was tested in vitro and in vivo. Normal cultured rat astrocytes and C6 rat glioma were used as a differential screen to test the effects of EDL-155. The compound was preferentially cytotoxic for C6 glioma (...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32830d5887
更新日期:2008-10-01 00:00:00