Abstract:
:Reduced drug accumulation may be one reason for intrinsic drug resistance in chronic lymphatic leukemia of the B-cell type (B-CLL). Immunophenotyped leukemic human B-cells from 38 cases of B-CLL were characterized for P-glycoprotein (PGP) content. In all, 30 cases of B-CLL were additionally analyzed for further parameters: accumulation of daunorubicin (DNR, n = 20) and rhodamine 123 (Rh123, n = 30) in both the presence and the absence of verapamil (VRP). Also, 16 cases of B-CLL were analyzed for vincristine (VCR) accumulation with or without VRP. Concerning the relative expression of PGP, these 16 cases of B-CLL were representative for the whole group of 30 cases. Spontaneous accumulation of Rh123 and VCR varied over a wide range: accumulation of Rh123, by a factor of 11.8; accumulation of VCR, by a factor of 9.7; and accumulation of DNR, by a factor of 3.6. VRP modulated the accumulation of RH123 in 16/30 cases (53%), that of VCR in 69% of cases, and that of DNR in 11% of cases. The maximal VRP-mediated increases in accumulation amounted to factors of 1.3 for DNR, 2.3 for Rh123, and 7.8 for VCR. Spontaneous drug accumulation did not correlate with the extent of chemomodulation. The amount of PGP in B-CLL cells (all cases studied were PGP-positive) did not correlate with drug accumulation or with the extent of VRP-mediated chemomodulation. Thus, high expression of PGP is only partially responsible for defective drug accumulation in B-CLL. Only the degree of chemomodulation by VRP is predictive for the extent of the PGP-related functional drug accumulation defect. Thus, in B-CLL, PGP-independent drug accumulation defects seem to be as important as those mediated by PGP. The extent of this drug accumulation defect varies for the different drugs in the following order VCR > Rh123 > DNR. The relevance of PGP-mediated and -independent drug accumulation defects in vivo may depend to a large extent on the drug being used and on the individual cell type. Both types of defect in drug accumulation are of high importance when regimens include VCR a drug commonly used in second-line chemotherapy of B-CLL. Both defects in drug accumulation may be responsible for intrinsic VCR resistance in B-CLL.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Reichle A,Diddens H,Altmayr F,Rastetter J,Andreesen Rdoi
10.1007/BF00686038subject
Has Abstractpub_date
1994-01-01 00:00:00pages
307-16issue
4eissn
0344-5704issn
1432-0843journal_volume
34pub_type
杂志文章abstract::Cell lines resistant to five antitumor alkylating agents (CDDP, PAM, 4-HC, HN2, and BCNU) were developed from five parental human tumor lines representative of solid tumors with a range of sensitivities to antitumor alkylating agents. The parental cell lines were SCC-25 squamous carcinoma of the head and neck, MCF-7 b...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685328
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone. METHODS:I...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3141-4
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. Although CPT and its derivatives are now being used to treat tumors in a variety of clinical protocols, the low water solubility of the drug and its unique pharmacodynamics and reactivity i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0463-1
更新日期:2002-08-01 00:00:00
abstract:PURPOSE:Valproic acid (VPA), a widely used antiepileptic, also inhibits histone deacetylase (HDAC), and is undergoing evaluation as an anti-cancer agent. We studied the pharmacokinetics of VPA in the plasma and cerebrospinal fluid (CSF) in a non-human primate model that is highly predictive of human CSF penetration to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0519-3
更新日期:2008-04-01 00:00:00
abstract::The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the poten...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-018-3541-8
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:To evaluate whether celecoxib alters the conversion of gemcitabine into its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral blood mononuclear cells (PBMCs). METHODS:Patients with advanced pancreatic cancer who had not received chemotherapy and had acceptable organ function were el...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0916-9
更新日期:2005-06-01 00:00:00
abstract:PURPOSE:Everolimus is a standard treatment option for advanced pancreatic neuroendocrine tumors (pNETs). This multicenter study evaluated the efficacy and safety of everolimus in low and intermediate grade advanced pNETs. METHODS:Tumors were graded according to the World Health Organization 2010 classification system....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3421-7
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00280-004-0993-9
更新日期:2005-10-01 00:00:00
abstract:PURPOSE:By a scaffold shortening strategy, a small series of retinoidal amides fenretinide (4-HPR) analogs have been synthesized from α, β-ionones and tested for their antiproliferative and differentiating activities, and antioxidant effect. METHODS:The antiproliferative activity and triggering of apoptosis of our sho...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3265-1
更新日期:2017-04-01 00:00:00
abstract::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 techniqu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050403
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:To assess the activity and safety of combined folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC) in metastatic breast cancer patients previously treated with at least two chemotherapy regimens. PATIENTS AND METHODS:A total of 104 consecutive patients were enrolled for treatment with FA 100 mg/m(2) ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-002-0495-6
更新日期:2002-10-01 00:00:00
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
doi:10.1007/s00280-016-3109-4
更新日期:2016-09-01 00:00:00
abstract::Purified human leukocyte interferon produced by recombinant techniques (IFN-alpha A) was tested in vitro with chemotherapeutic drugs, vinblastine (VLB), vincristine (VCR), vindesine (VDS), vinzolidine (VZL), cis-platinum (PLAT), doxorubicin (DOXO), etoposide (VP-16), and melphalan (MEL). The activity of these agents a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255753
更新日期:1983-01-01 00:00:00
abstract::Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-F...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686944
更新日期:1992-01-01 00:00:00
abstract::Prostaglandins (PGs) have been shown to inhibit tumour metastases in experimental animal systems. Nafazatrom is a pyrazolinone derivative that increases endogenous prostacyclin (PGI2) and has experimental anti-cancer activity. In the present study, nafazatrom was given to 47 women with advanced breast cancer; objectiv...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00685120
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Pemetrexed, a multi-targeted antifolate that disrupts synthesis of both purines and pyrimidines, is approved for use in malignant pleural mesothelioma and non-small cell lung cancer. Pemetrexed is currently being evaluated for anti-tumor activity in a variety of solid and central nervous system tumors. We studi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0285-7
更新日期:2007-03-01 00:00:00
abstract:PURPOSE:2-Methoxyestradiol (2-ME) is a physiological metabolite of estrogen, which can inhibit growth of many types of tumor cells, including hepatocellular carcinoma, both in vitro and in vivo. The exact mechanisms of its action are still unclear. We have studied the mechanisms of growth inhibition of several of human...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0670-x
更新日期:2008-10-01 00:00:00
abstract::The pharmacokinetics of diacetyldianhydrogalactitol (DADAG) was compared in mice, rats, and humans. The ratios of human therapeutic dose (ThD) to the LD10 were 8 and 5 in mice and rats, respectively. The ratios of the corresponding AUCs of DADAG were 20 and 17, whereas those of dianhydrogalactitol (DAG), the main, act...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257306
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:To evaluate the antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular disrupting agent currently under phase II clinical trials in combination with cancer chemotherapy, in rats bearing chemically induced primary mammary tumours. METHODS:Tumours were induced in female Wistar rats by in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0321-7
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile. METHODS:Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flav...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2347-y
更新日期:2014-02-01 00:00:00
abstract::Carmustine (BCNU) has proved to be of value against a variety of primary brain tumors. This agent exhibits a steep dose-response curve in in vitro and animal tumor models and has been proposed for use in high-dose chemotherapy as a single agent or in combination. We conducted a phase II study to assess high-dose BCNU ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050586
更新日期:1997-01-01 00:00:00
abstract::The selective Aurora-A kinase inhibitor MLN8237 is in clinical trials for hematologic malignancies, ovarian cancer and other solid tumors. We previously showed that MLN8237 is potently antiproliferative toward standard monolayer-cultured glioblastoma cells. We have now investigated the effect of MLN8237 with and witho...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2430-z
更新日期:2014-05-01 00:00:00
abstract::Comparative in vitro drug testing was performed in 72 of 183 surgically removed human colorectal cancer specimens (34 primary lesions, 38 metastases). In 10 of these tumors, comparative dose-response curves were obtained. Given a greater than or equal to 70% ICF (inhibition of colony formation) as threshold for in vit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00273390
更新日期:1986-01-01 00:00:00
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
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available. METHODS:We searched the FDA MedWatch database for TMZ and obtained all MedWatch reports on TMZ submitted to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1679-8
更新日期:2012-01-01 00:00:00
abstract::The effect of 7-alkyl substitutions on growth inhibition in seven Camptothecin (CPT) ring systems with various groups at the ten position was evaluated in three human breast cancer cell lines that model (1) hormone-sensitive (MCF-7/wt), (2) hormone insensitive (MDA-MB-231), or (3) alkylator-resistant (MCF-7/4-hc) form...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0007-6
更新日期:2006-01-01 00:00:00
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
doi:10.1007/s00280-008-0917-1
更新日期:2009-09-01 00:00:00
abstract:PURPOSE:Carboplatin is frequently dosed to achieve a desired area under the plasma concentration-time curve (AUC) by using the Calvert or Chatelut equations to estimate carboplatin clearance. Accurate determination of glomerular filtration rate (GFR) is necessary to correctly calculate carboplatin clearance using the C...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000260
更新日期:2001-05-01 00:00:00
abstract:PURPOSE:Sonidegib (Odomzo) selectively inhibits smoothened and suppresses the growth of hedgehog pathway-dependent tumors. A population pharmacokinetic (PK) analysis of sonidegib in healthy subjects and patients with advanced solid tumors was conducted to characterize PK, determine variability, and estimate covariate e...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-2982-1
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:This study aimed at evaluating if pharmacokinetic and pharmacodynamic data from the first few patients treated with an investigational monoclonal antibody in a dose-escalation study can be used to guide the early initiation of potentially more efficacious combination regimens. METHODS:Emerging pharmacokinetic ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3328-3
更新日期:2017-06-01 00:00:00