Abstract:
:Dexniguldipine-HCl (DNIG)--a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MDR)--was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR), or mitoxantrone (MITO) in resistant F4-6RADR cells to the very levels observed in drug-sensitive F4-6 precursor cells. In parallel with the increase in DNR content (F4-6RADR, solvent: 303 +/- 27 pmol/mg protein; DNIG (3.3 mumol/l): 1,067 +/- 174 pmol/mg protein; F4-6P, solvent: 948 +/- 110 pmol/mg protein; n = 8-9, SEM), the amount of DNR tightly bound to the acid precipitate pellet obtained from F4-6RADR (i.e., protein, DNA, RNA) increased 3.9-times to the levels observed in sensitive F4-6 cells. The main pyridine metabolite of DNIG displayed similar activity. Concentration-response analysis revealed that DNIG and R,S-verapamil (VER) induced 100% reversal of the DNR accumulation shortage associated with the MDR phenotype but DNIG was 8 times more potent than VER (50% inhibitory concentration (IC50), 0.73 vs 5.4 mumol/l). In keeping with the accumulation assay, DNIG was about 10 times more potent than VER in sensitizing F4-6RADR cells to the cytostatic and cytotoxic effects of DNR in proliferation assays. In conclusion, DNIG is a potent in vitro modulator, improving (a) the accumulation of anthracycline-like cytostatics, (b) drug access to cellular binding sites, and (c) the cytostatic action of DNR in F4-6RADR leukemia cells of the MDR phenotype.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Reymann A,Looft G,Woermann C,Dietel M,Erttmann Rdoi
10.1007/BF00685872subject
Has Abstractpub_date
1993-01-01 00:00:00pages
25-30issue
1eissn
0344-5704issn
1432-0843journal_volume
32pub_type
杂志文章abstract::The pharmacokinetics of soluble oral prednisolone were studied during induction therapy in six children with acute lymphoblastic leukaemia. There was a three- to four-fold variation in the pharmacokinetics of total and free prednisolone. For total prednisolone, the mean elimination half-life was relatively short (1.37...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435843
更新日期:1989-01-01 00:00:00
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
更新日期:1994-01-01 00:00:00
abstract::A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of greater than 200%...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00267943
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:Mutations and activations of the MEK and PI3K pathways are associated with the development of many cancers. GDC-0973 and GDC-0941 are inhibitors of MEK and PI3K, respectively, currently being evaluated clinically in combination as anti-cancer treatment. The objective of these studies was to characterize the rel...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1988-6
更新日期:2013-01-01 00:00:00
abstract::Unidirectional blood-brain barrier transfer of the lipophilic anticancer agents vincristine and vinblastine was studied in anesthetized rats, using an isolated, in situ brain perfusion technique. Drug binding to plasma constituents was also measured. Despite the high lipophilicity of these agents (the log octanol/phys...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897227
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Nephrotoxicity is one of the major dose-limiting side-effects of cisplatin (DDP). The disproportionate accumulation of cisplatin in kidney tissue may play an important role, however, therapeutic measures to prevent this prime cause of nephrotoxicity are not available. Because certain amino acids (AAs) have been...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/PL00006741
更新日期:2000-01-01 00:00:00
abstract::A major side effect of cisplatin treatment is peripheral neuropathy. In the past few years we have provided evidence that the ACTH4-9 analogue ORG 2766 provides protection against this neuropathy in rats and man. In this study we investigated the development of a cisplatin-induced neuropathy and the protective and the...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685621
更新日期:1993-01-01 00:00:00
abstract::The oral bioavailability of methotrexate is variable and may be dose-dependent. The absorption of 'interval' oral methotrexate, which is given between cycles of chemotherapy, is unknown. The bioavailability of oral methotrexate has been studied in eight patients, acting as their own controls, to assess the effect of s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257121
更新日期:1984-01-01 00:00:00
abstract::The purpose of this study was to determine long-term renal platinum excretion after chemotherapy with cisplatin. We examined urinary platinum concentrations in 23 men at 150-3022 days after anticancer treatment for testicular neoplasm. Spot urine samples were analyzed by voltammetry. This new, subtle method with a det...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685736
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Human type I fatty acid synthase has been proposed as a chemotherapeutic target for the treatment of breast cancer based on the inactivation of human beta-ketoacyl synthase activity by cerulenin. Triclosan, a common antibiotic, functions by inhibiting the enoyl-reductase enzymes of type II fatty ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-001-0399-x
更新日期:2002-03-01 00:00:00
abstract:PURPOSE:The blood-brain barrier discriminates the access of several molecules to the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine pretreatment, to a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1429-3
更新日期:2011-06-01 00:00:00
abstract:PURPOSE:Isobologram analysis has been widely used for evaluating the combined effect of two antitumor drugs in vitro as a pre-clinical screening test. In this study, we tried to extend two-dimensional isobologram analysis to three dimensions for evaluating the effects of a three-drug combination. METHODS:We selected t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050560
更新日期:1997-01-01 00:00:00
abstract::A series of in vitro cytotoxicity studies were performed to achieve pharmacologic reversal of resistance to the alkylating agent mitomycin (MMC) in L-1210 leukemia cells. A multidrug-resistant (MDR), P-glycoprotein-positive cell line, RL-1210/.1 [11], was exposed to potential MDR modulators in the absence or presence ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685114
更新日期:1991-01-01 00:00:00
abstract::O-6-methylguanine (O6-mG), a guanine analog recently shown to be a potent inhibitor of alkylguanine-DNA alkyltransferase, has been found to potentiate the antitumor activity of nitrosoureas, in particular, carmustine (BCNU), in resistant cell lines (HT-29 mer+) and is targeted for development as a modulating agent wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686216
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Imatinib mesylate (Imatinib), clinically employed for chronic myeloid leukemia and gastrointestinal stromal tumors, is a selective inhibitor of the tyrosine kinases, c-abl, c-kit and PDGFRs. Due to the frequent expression of these genes in breast cancer cells, the clinical efficacy of Imatinib has recently been...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1394-x
更新日期:2011-04-01 00:00:00
abstract::A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435840
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:Leucovorin is commonly used as folate supplement in 5-fluorouracil-based chemotherapy, but needs to be converted to active 5,10-methylenetetrahydrofolate (methyleneTHF) intracellularly. This provides for interindividual differences. MethyleneTHF has recently been developed into the stable, distributable drug, M...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-014-2611-9
更新日期:2015-01-01 00:00:00
abstract::A patient with acute nonlymphoblastic leukemia in relapse and anthracycline cardiomyopathy was treated with AMSA in combination with cytosine arabinoside and thioguanine (AAT). Induction of remission was accomplished after one course of therapy without development of congestive heart failure. Radionuclide studies done...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257232
更新日期:1982-12-01 00:00:00
abstract:PURPOSE:To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS:We analyzed retrospectively the data ...
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/s002800050689
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:To assess the clinical activity and toxicity of a combination chemotherapy regimen of S-1 and cisplatin in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in a retrospective study. METHODS:A total of 49 patients were treated in an outpatient setting with S-1 80 mg/m(2) o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1933-8
更新日期:2012-10-01 00:00:00
abstract:PURPOSE:The dolastatins are a class of naturally occurring cytotoxic peptides which function by inhibiting microtubule assembly and tubulin polymerization. Cemadotin is a synthetic analogue of dolastatin 15 with potent antiproliferative and preclinical antitumor activity. This report describes a phase I study to evalua...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800000152
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resis...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-018-3677-6
更新日期:2018-11-01 00:00:00
abstract::This phase I study was carried out to determine the maximal tolerated dose of carboplatin (Car) together with a fixed dose of etoposide (E) and to recommend the optimal dose for a phase II study. The dose of E was 100 mg/m2 given i.v. on days 1-3, and the starting dose of Car was 200 mg/m2 given i.v. on day 1. The dos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00685718
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration. METHODS:ABT-8...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1044-3
更新日期:2010-02-01 00:00:00
abstract:PURPOSE:P-glycoprotein (P-gp), encoded by MDR1 (or ABCB1), is important in anticancer drug delivery and resistance. We evaluated alterations in P-gp-mediated transport of anticancer agents due to the MDR1 G1199A polymorphism. METHODS:Using stable recombinant epithelial cells expressing wild-type (MDR1 (wt)) or G1199A ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0906-4
更新日期:2009-06-01 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:BACKGROUND:Pre-clinical activity of SSG against melanoma and renal cancer has been identified recently although the drug's mechanism of action and activity against tumors of additional histological-types remain undefined. METHODS:The effects of SSG and SSG combination with other agents on DU145 human prostate carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0378-3
更新日期:2007-08-01 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:PURPOSE:Aldehyde dehydrogenases class-1A1 (ALDH1A1) and class-3A1 (ALDH3A1) have been associated with resistance to cyclophosphamide (CP) and its derivatives. We have previously reported the downregulation of these enzymes by all-trans retinoic acid (ATRA). METHODS:In this study, we used siRNA duplexes as well as retr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0233-6
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:Following promising responses to the DNA methyltransferase (DNMT) inhibitor 5-fluoro-2'-deoxycytidine (FdCyd) combined with tetrahydrouridine (THU) in phase 1 testing, we initiated a non-randomized phase 2 study to assess response to this combination in patients with advanced solid tumor types for which tumor s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04073-5
更新日期:2020-05-01 00:00:00