Imidazoacridinones arrest cell-cycle progression in the G2 phase of L1210 cells.


: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.


Augustin E,Wheatley DN,Lamb J,Konopa J




Has Abstract


1996-01-01 00:00:00












  • Effects of DFMO-induced polyamine depletion on human tumor cell sensitivity to antineoplastic DNA-crosslinking drugs.

    abstract::We investigated the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to two alkylating and crosslinking agents: chlorambucil and N,N',N"-triethylenethiophosphoramide (thiotepa). The cell lines studied in...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Seidenfeld J,Komar KA,Naujokas MF,Block AL

    更新日期:1986-01-01 00:00:00

  • Alkylphosphocholines: influence of structural variation on biodistribution at antineoplastically active concentrations.

    abstract::Hexadecylphosphocholine (HPC) and octadecylphosphocholine (OPC) show very potent antitumor activity against autochthonous methylnitrosourea-induced mammary carcinomas in rats. The longer-chain and unsaturated homologue erucylphosphocholine (EPC) forms lamellar structures rather than micelles, but nonetheless exhibits ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kötting J,Berger MR,Unger C,Eibl H

    更新日期:1992-01-01 00:00:00

  • MiniPDX-guided postoperative anticancer treatment can effectively prolong the survival of patients with hepatocellular carcinoma.

    abstract:BACKGROUND:The recurrence rate of hepatocellular carcinoma (HCC) after partial hepatectomy is still high. How to choose the most appropriate anti-tumor drug in the early postoperative period is crucial to improve the prognosis of patients. Recently, MiniPDX has been widely used as a new and reliable preclinical researc...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Yang L,Yuan Z,Zhang Y,Cui Z,Li Y,Hou J,Liu X,Liu Z,Shi R,Tian Q,Wang J,Wang L

    更新日期:2021-01-01 00:00:00

  • Population pharmacokinetics of sonidegib (LDE225), an oral inhibitor of hedgehog pathway signaling, in healthy subjects and in patients with advanced solid tumors.

    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


    authors: Goel V,Hurh E,Stein A,Nedelman J,Zhou J,Chiparus O,Huang PH,Gogov S,Sellami D

    更新日期:2016-04-01 00:00:00

  • Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine.

    abstract::Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kralovanszky J,Prajda N,Kerpel-Fronius S,Bagrij T,Kiss E,Peters GJ

    更新日期:1993-01-01 00:00:00

  • Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer.

    abstract:PURPOSE:To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were includ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Feliu J,Martín G,Castro J,Sundlov A,Rodriguez-Jaráiz A,Casado E,Lomas M,Madroñal C,Galán A,Belda C,Gonzalez-Barón M

    更新日期:2006-10-01 00:00:00

  • Protein expression profiling identifies differential modulation of homologous recombination by platinum-based antitumor agents.

    abstract:PURPOSE:Oxaliplatin and satraplatin demonstrate activity against cisplatin-resistant tumor cells. Although the two platinum analogs are structurally-related, oxaliplatin is more active. Therefore, studies focusing on protein expression profiling were undertaken to identify the molecular mechanism for the difference in ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: He G,Xie X,Siddik ZH

    更新日期:2020-06-01 00:00:00

  • Cisplatin-based combination chemotherapy for elderly patients with non-small-cell lung cancer.

    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


    authors: Kubota K,Furuse K,Kawahara M,Kodama N,Ogawara M,Takada M,Masuda N,Negoro S,Matsui K,Takifuji N,Kudoh S,Kusunoki Y,Fukuoka M

    更新日期:1997-01-01 00:00:00

  • Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals.

    abstract:PURPOSE:For the development of a safe and effective dual inhibitor of anticancer drug efflux transporters P-glycoprotein and multidrug resistance protein 1 (MRP1) to conquer multidrug resistance, we investigated the effects of dietary phytochemicals on the functions of P-glycoprotein and MRP1. METHODS:The effects of d...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Nabekura T,Yamaki T,Ueno K,Kitagawa S

    更新日期:2008-10-01 00:00:00

  • Taxol cytotoxicity on human leukemia cell lines is a function of their susceptibility to programmed cell death.

    abstract::Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Gangemi RM,Tiso M,Marchetti C,Severi AB,Fabbi M

    更新日期:1995-01-01 00:00:00

  • Effects of prochlorperazine on experimental nephrotoxicity.

    abstract::In early studies of the antitumor drug 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1nitrosourea (methyl-CCNU), animal models consistently predicted that the compound would be nephrotoxic in humans. Nephrotoxicity in cancer patients who had received methyl-CCNU was not confirmed until about 6 years after clinical trials b...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Harrison SD Jr,Cox JL,Giles RC Jr

    更新日期:1982-12-01 00:00:00

  • SM-1, a novel PAC-1 derivative, activates procaspase-3 and causes cancer cell apoptosis.

    abstract:PURPOSE:To develop more potent procaspase-3 activator, 7 novel derivatives of PAC-1 were synthesized and evaluated. Among them, SM-1 stood out for its promising activity and good pharmacokinetics properties. The purpose of this study is to elucidate the pharmacological mechanism of SM-1 and evaluate its efficacy and to...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Chen Y,Sun M,Ding J,Zhu Q

    更新日期:2016-09-01 00:00:00

  • Phase II study of S-1 as first-line treatment for elderly patients over 75 years of age with advanced gastric cancer: the Tokyo Cooperative Oncology Group study.

    abstract:PURPOSE:This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer. METHODS:Patients had measurable or evaluable lesions according to the Japanes...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Koizumi W,Akiya T,Sato A,Sakuyama T,Sasaki E,Tomidokoro T,Hamada T,Fujimori M,Kikuchi Y,Shimada K,Mine T,Yamaguchi K,Sasaki T,Kurihara M

    更新日期:2010-05-01 00:00:00

  • CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone.

    abstract:BACKGROUND:Abiraterone became a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Crucitta S,Del Re M,Paolieri F,Bloise F,Sbrana A,Sammarco E,Mercinelli C,Cucchiara F,Fontanelli L,Galli L,Danesi R

    更新日期:2020-10-01 00:00:00

  • Chromatographic characterisation of six human metabolites of the new anticancer drug GR63178A.

    abstract::GR63178A is the second pentacyclic pyrroloquinone to enter clinical trials as an anticancer drug. We developed a reversed-phase, gradient-elution high-performance liquid chromatography (HPLC) method along with a Bond Elut C2 mini-column sample-preparation technique for the analysis of GR63178A, its 9-hydroxy-metabolit...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Cummings J,French RC,MacLellan A,Smyth JF

    更新日期:1991-01-01 00:00:00

  • Methotrexate removal during haemodialysis in a patient with advanced laryngeal carcinoma.

    abstract::A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy. The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received thr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Thomson AH,Daly M,Knepil J,Harden P,Symonds P

    更新日期:1996-01-01 00:00:00

  • Combination chemotherapy including adriamycin for advanced transitional cell carcinoma of the urinary tract.

    abstract::Thirty-three patients with advanced transitional cell carcinoma of the urinary tract (23 bladder cases, 8 ureter cases, and 2 renal pelvis cases) were treated by three-drug combination chemotherapy using two protocols (protocol I: Adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 500 mg/m2, protocol ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kotake T,Usami M,Miki T,Kuroda M,Obata K,Osafune M,Fujioka H,Takasugi Y

    更新日期:1983-01-01 00:00:00

  • Methylprednisolone as an antiemetic drug. A randomised double blind study.

    abstract::To evaluate the antiemetic efficacy of high-dose methylprednisolone (MP) in previously untreated cancer patients receiving cisplatin (CPDD) for the first time, we performed a randomized double blind study. MP or a placebo (PLB) was administered six times during each course of chemotherapy. The first dose was 500 mg an...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Schallier D,Van Belle S,De Greve J,Willekens A

    更新日期:1985-01-01 00:00:00

  • Evaluation of p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl against transplantable and spontaneous murine neoplasia.

    abstract::The therapeutic efficacy of PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable L1210 leukemia and Ridgway osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary tumor and AKR leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Yagi MJ,Bekesi JG

    更新日期:1990-01-01 00:00:00

  • Retrospective comparison of toxicity and efficacy in phase II trials of 3-h infusions of paclitaxel for patients 70 years of age or older and patients under 70 years of age.

    abstract:PURPOSE:To evaluate the safety and efficacy of paclitaxel in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS:We compared the toxicity, response, survival and pharmacokinetic parameters between patients between 70 and 75 years of age (elderly group) and those under 70 years of age (younger gr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Nakamura Y,Sekine I,Furuse K,Saijo N

    更新日期:2000-01-01 00:00:00

  • Further characterization of the sixth transmembrane domain of Pgp1 by site-directed mutagenesis.

    abstract:PURPOSE:Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side coul...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Song J,Melera PW

    更新日期:2001-11-01 00:00:00

  • High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study.

    abstract::A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Carmo-Pereira J,Costa FO,Miles DW,Henriques E,Richards MA,Rubens RD

    更新日期:1991-01-01 00:00:00

  • Physicochemical and pharmacokinetic parameters of seven lipophilic chlorambucil esters designed for brain penetration.

    abstract::This report describes the physicochemical and pharmacokinetic parameters of seven chlorambucil esters, which were compared with those of chlorambucil. These esters were designed as chlorambucil prodrugs to increase the brain penetration and concentration vs time profile of chlorambucil within the CNS for potential tre...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Greig NH,Genka S,Daly EM,Sweeney DJ,Rapoport SI

    更新日期:1990-01-01 00:00:00

  • Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications.

    abstract::Carboxypeptidase G2 (CPG2) is used when unexpected toxicity or renal failure occurs during high-dose methotrexate therapy. Leucovorin is also administered to antagonise the effects of methotrexate on purine anabolism. To investigate the effects of CPG2 on leucovorin rescue, we incubated the enzyme with both stereoisom...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Hempel G,Lingg R,Boos J

    更新日期:2005-04-01 00:00:00

  • ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein.

    abstract:PURPOSE:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective cytotoxicity to transformed cells. However, most human hepatocellular carcinomas (HCC) develop resistance to TRAIL. Thus, there is an urgent need to investigate the molecular targets and the unde...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Wang G,Zhan Y,Wang H,Li W

    更新日期:2012-03-01 00:00:00

  • Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer.

    abstract:PURPOSE:S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ishiwatari H,Hayashi T,Yoshida M,Ono M,Sato T,Miyanishi K,Sato Y,Takimoto R,Kobune M,Kato J

    更新日期:2015-04-01 00:00:00

  • Phase II study of hepatic artery infusion with 5-fluorouracil, adriamycin, and mitomycin C (FAM) in liver metastases from colorectal carcinoma.

    abstract::Twenty-seven patients with liver metastases from colorectal carcinoma were treated with 5-fluorouracil, adriamycin, and mitomycin C (FAM) by hepatic artery infusion (HAI) every 2-3 months for a maximum of eight courses. Median survival for all patients was 22 months. Toxicity was acceptable and consisted in severe mye...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Wils J,Schlangen J,Naus A

    更新日期:1984-01-01 00:00:00

  • A phase I study to investigate the metabolism, excretion, and pharmacokinetics of [14C]fruquintinib, a novel oral selective VEGFR inhibitor, in healthy Chinese male volunteers.

    abstract:PURPOSE:Fruquintinib (HMPL-013) is a novel, potent, and highly selective tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptors (1, 2 and 3). This study was conducted to investigate the metabolism, excretion, and pharmacokinetics of HMPL-013 after a single oral dose to healthy Chinese men....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Zhou S,Shao F,Xu Z,Wang L,Jin K,Xie L,Chen J,Liu Y,Zhang H,Ou N

    更新日期:2017-09-01 00:00:00

  • Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants. Rational individualization

    abstract:PURPOSE:Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular conte...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Sreerama L,Sládek NE

    更新日期:2001-03-01 00:00:00

  • A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer.

    abstract:PURPOSE:There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kobayashi T,Koizumi T,Agatsuma T,Yasuo M,Tsushima K,Kubo K,Eda S,Kuraishi H,Koyama S,Hachiya T,Ohura N

    更新日期:2012-05-01 00:00:00