Abstract:
:Imidazoacridinones are a new class of highly potent antineoplastic agents synthesised at the Technical University of Gdansk. The pharmacophoric alkyldiamine group, which is also present in anthracenediones (e.g. ametantrone, mitoxantrone), has been shown to be responsible for their antineoplastic activity. In view of their chemical similarity to anthracenediones, we anticipated that the imidazoacridinones would have a mechanism of action similar to that of these agents and that this would be reflected by a similar influence on cell-cycle progression. Flow cytometry was used to monitor the effect of three derivatives of imidazoacridinone (C-1263, C-1310 and C-1311) on L1210 cell cycle traverse at concentrations ranging from 0.01 to 0.9 microgram/ml, corresponding to their 50% and 90% effective concentrations (EC50 and EC90 values), over times of drug treatment ranging from 1 to 48 h. The results demonstrate that all of the compounds produced a similar effect, inducing preferential and complete arrest (accumulation) of cells in the G2 phase of the cell cycle (i.e. G2 block). The kinetics of the induction of G2 arrest were dependent on both the dose and the duration of treatment. Cell-cycle arrest was reversible for up to about 3 h of treatment, being quite irreversible at longer incubation times. Microscopic inspection of cells performed in parallel with flow cytometry confirmed that imidazoacridinones induced a G2, not a G2/M, block.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Augustin E,Wheatley DN,Lamb J,Konopa Jdoi
10.1007/s002800050445subject
Has Abstractpub_date
1996-01-01 00:00:00pages
39-44issue
1eissn
0344-5704issn
1432-0843journal_volume
38pub_type
杂志文章abstract:PURPOSE:This study was performed to determine whether or not in cervical, ovarian and lung cancer cell lines, free radicals (ROS) play a role in cisplatin cytotoxicity and activation of the mitochondrial and JNK/p38 pathways. The role of the enzyme, dihydrodiol dehydrogenase (DDH1), in the activation/deactivation of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2739-2
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:This phase I clinical trial evaluated the safety, tolerability, and pharmacokinetics of high-dose intravenous (i.v.) ascorbic acid as a monotherapy in patients with advanced solid tumors refractory to standard therapy. METHODS:Five cohorts of three patients received i.v. ascorbic acid administered at 1 g/min f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2179-9
更新日期:2013-07-01 00:00:00
abstract::Tumor angiogenesis is essential for tumor growth and metastasis formation. Luminex methodology was used to measure the levels of four angiogenic cytokines in cell culture medium and in the plasma of mice bearing human tumors. We obtained plasma and conditioned culture medium from 12 different human tumor cell lines. T...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0572-5
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1744-3
更新日期:2012-03-01 00:00:00
abstract:PURPOSE:To investigate any effect of a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) on cediranib steady-state pharmacokinetics in patients with advanced solid tumours. METHODS:In two Phase I, open-label trials, patients received once-daily oral doses of cediranib alone [20 mg (ketoconazole study); 45 mg (ri...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2038-0
更新日期:2013-02-01 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::Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257744
更新日期:1982-01-01 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:Patupilone (EPO906) is a novel potent microtubule stabilizer, which has been evaluated for cancer treatment. A novel physiologically based pharmacokinetics (PBPK) model was developed based on nonclinical data to predict the disposition of patupilone in cancer patients. METHODS:After a single intravenous dose (...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1863-5
更新日期:2012-06-01 00:00:00
abstract::Over the last decade, metronomic chemotherapy has been increasingly considered as an attractive strategy for treating cancer in a variety of settings. Beside pharmaco-economic considerations making metronomics a unique opportunity in low- or middle-income countries, revisiting dosing schedules using continuous low dos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2546-1
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2312-9
更新日期:2013-12-01 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:BACKGROUND:Veliparib (ABT-888) is an oral PARP inhibitor expected to increase gemcitabine activity. This phase I determined the maximal tolerable dose (MTD), dose-limiting toxicities (DLT), antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib combined with gemcitabine. METHODS:Patients wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3409-3
更新日期:2017-09-01 00:00:00
abstract:PURPOSE:There is a need to find novel oestrogen receptor (ER) ligands that antagonize oestrogen action in the reproductive tissues and would therefore have therapeutic potential in oestrogen-dependent tumours. We tested novel ER ligands in both breast and endometrial cells to profile agonism/antagonism in these oestrog...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000259
更新日期:2001-05-01 00:00:00
abstract:PURPOSE:Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0263-0
更新日期:2007-02-01 00:00:00
abstract::The pharmacokinetics of pentamethylmelamine (PMM) have been investigated in mouse (Balb C-, CBA/LAC, nude), rat (Wistar), and man. In all three species, PMM was extensively demethylated to N2,N2,N4,N6-tetramethylmelamine and N2,N4,N6-trimethylmelamine, although marked species differences in the rate of metabolism were...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00292880
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:Arsenic compounds have been found to be effective in the treatment of acute promyelocytic leukemia through the downregulation of bcl-2 expression. Resistant ovarian cancer cells often overexpress bcl-2 or p53 proteins or both. We hypothesized that arsenic compounds, such as As2O3 and As2S3, could also be active...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100278
更新日期:2001-06-01 00:00:00
abstract:PURPOSE:We examined the interaction between cyclophosphamide (CPA) and angiostatin (AS) on the growth of primary Lewis lung carcinoma (LLC) tumors and on the development of LLC pulmonary metastases. We studied the effects of AS and CPA on the stages of angiogenesis employing in vitro assays. METHODS:Primary tumor grow...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0514-7
更新日期:2002-11-01 00:00:00
abstract:PURPOSE:P-glycoprotein is a 170-kDa plasma membrane multidrug transporter that actively exports cytotoxic substances from cells. Overexpression of P-glycoprotein by tumor cells is associated with a multidrug-resistant phenotype. Immunosuppressive agents such as cyclosporins and macrolides, have been shown to attenuate ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050960
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:We studied EGFR mutations in circulating tumor DNA (ctDNA) and explored their role in predicting the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients treated with erlotinib or gefitinib. METHODS:The L858R, T790M mutations and exon 19 deletions were quantified in plasma using digit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-021-04230-4
更新日期:2021-01-23 00:00:00
abstract:PURPOSE:To determine the maximum tolerated dose and the toxicity profile of the PDGF receptor pathway inhibitor SU101 in pediatric patients with refractory solid tumors, and to define the plasma pharmacokinetics of SU101 and its active metabolite SU0020 in children. EXPERIMENTAL DESIGN:Patients between 3 and 21 years ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0769-2
更新日期:2004-06-01 00:00:00
abstract:PURPOSE:To gain a better understanding of the impact of postprogression survival (PPS) and post-trial anticancer therapy on overall survival (OS) in first-line pancreatic cancer patients. METHODS:A literature search identified 54 randomized trials, focusing on gemcitabine monotherapy to eliminate effects of heterogene...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-017-3263-3
更新日期:2017-03-01 00:00:00
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
更新日期:1998-01-01 00:00:00
abstract::Macroautophagy is widely accepted as a cytoprotective mechanism against various environmental stresses. While inhibition of autophagy is generally considered to increase the susceptibility of cancer cells to therapeutic agents, whether it also plays a similar role in tumor stem cells is unclear and still controversial...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2634-2
更新日期:2015-05-01 00:00:00
abstract::Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirub...
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/BF00685824
更新日期:1991-01-01 00:00:00
abstract::Seventy-three patients with Dukes' B2 and C colorectal cancer were randomized to adjuvant therapy after radical surgery. One group was treated with chemotherapy either alone or in combination with radiotherapy (RC). The second group was treated by chemotherapy (with or without radiotherapy) plus MER/BCG (RCM). In pati...
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/BF00292869
更新日期:1982-01-01 00:00:00
abstract::The antimetabolite 1-beta-D-arabinofuranosyl-cytosine (ara-C) has proven to be one of the most effective agents available for the treatment of acute leukemia. While ara-C has been implicated as a potent inhibitor of mammalian cell DNA replication, the specific mechanism by which ara-C kills cells is not known. In this...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050496
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:The chimeric protein BCR-ABL, a constitutively active protein-tyrosine kinase, triggers downstream signalling proteins, such as STAT3, ultimately resulting in the survival of myeloid progenitors in BCR-ABL-positive leukemias. Here, we evaluated the effect of LLL-3, an inhibitor of STAT3 activity, on cell viabil...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1109-3
更新日期:2010-05-01 00:00:00
abstract::Studies are described in which a new folate analogue, edatrexate (EDX), in combination with the vinca alkaloids, vinblastine (VBL), navelbine (NVB) or vindesine (DVA) was evaluated against E0771 mammary adenocarcinoma, T241 fibrosarcoma and the Lewis lung tumor. Each of the four agents when given individually to anima...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685901
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Although cisplatin is an important agent in non-small-cell lung cancer (NSCLC), de novo resistance is common and acquired resistance emerges rapidly during therapy. Proposed mediators of platinum resistance include the protein kinase C (PKC) signal transduction pathway and associated c-FOS overexpression. While...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800100293
更新日期:2001-07-01 00:00:00