Abstract:
PURPOSE:The present study was designed to investigate the ability of N-[4-(5-bromo-2-pyrimidyloxy)-3-methylphenyl]-(dimemethylamino)-benzoylphenylurea (dimemethylamino benzoylphenylurea; BPU) to sensitize cells to radiation and to examine the relationship between phenotype versus survival, DNA damage, apoptosis, or cell cycle progression in non-small cell lung cancer (NSCLC) cell lines. METHODS:Asynchronous cultures of three NSCLC (phenotype) lines, A549 (adenocarcinoma), NCI-H226 (squamous) and NCI-H596 (adenosquamous) were used. Cells were treated for 24 h with BPU at various concentrations (0-10 microM) to obtain drug doses for inhibiting cell survival by approximately 50% (IC50). Cells were X-irradiated without BPU or after 24 h BPU treatment at IC50. Radiation doses ranged from 0 to10 Gy. Cell survival was determined by a colony-forming ability assay. The effect of BPU on the cell cycle distribution and induction of apoptosis were measured by flow cytometry-based assays. The effect of BPU on radiation-induced DNA damage and repair was analyzed according to nuclear gammaH2AX immunofluorescence of cells exposed to X-rays alone or after BPU. Anti-gammaH2AX antibody staining, a surrogate determinant of double stranded DNA breaks, was measured using flow cytometry. RESULTS:BPU (1.5 microM) for 24 h produced approximately 50% cell survival. BPU and X-irradiation were synergistic in the three cell lines at survival levels of 20-50%. Flow cytometry analysis of replicate experiments with BPU (1.5 microM for 24 h) showed that BPU blocked cell progression at S and/or G2/M. The incidence of apoptosis in BPU-treated versus control cells ranged from approximately 0.3 to approximately 8%. Twenty-four hour after X-irradiation cells pre-treated with BPU and X-irradiated after drug exposure showed gammaH2AX levels approximately two times higher than did the cells exposed to X-rays only. CONCLUSIONS:The study identified BPU as a novel radiation sensitizer. The analysis of phosphorylated histone H2AX as a surrogate marker of DNA double strand breaks suggested a positive association between radiosensitization and the inhibition of X-irradiation-induced DNA damage repair by BPU.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Balcer-Kubiczek EK,Attarpour M,Edelman MJdoi
10.1007/s00280-006-0333-3subject
Has Abstractpub_date
2007-05-01 00:00:00pages
781-7issue
6eissn
0344-5704issn
1432-0843journal_volume
59pub_type
杂志文章abstract::The primary development of clinical resistance to 1-beta-D-arabinofuranosyl cytosine (ara-C) in leukemic blast cells is expressed as decreased cellular concentrations of its active anabolite. Correlations exist between the cellular concentrations of 1-beta-D-arabinofuranosyl cytosine 5'-triphosphate (ara-CTP) in leuke...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257619
更新日期:1989-01-01 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
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doi:10.1007/s00280-005-0007-6
更新日期:2006-01-01 00:00:00
abstract::Epirubicin (4'-epidoxorubicin), an analogue of doxorubicin (Adriamycin), has established activity in the treatment of small-cell lung cancer (SCLC) when used at doses of 75 to 120 mg/m2 in previously untreated patients. We completed a phase II study of epirubicin (85 mg/m2 given intravenously at 3-week intervals) in 2...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/BF00685514
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVES:To assess the cardiovascular safety, tolerability and efficacy of high doses of granisetron for the treatment of nausea and vomiting in patients undergoing highly emetogenic chemotherapy. METHODS:Patients with histologically confirmed malignant disease were given an intravenous infusion of granisetron, 160 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0689-6
更新日期:2004-02-01 00:00:00
abstract::In this review of the management of invasive carcinoma of the bladder the results of primary and systemic therapies are evaluated in the light of the natural history of the disease. The clinical and pathological causes of treatment failure are assessed in an attempt to identify new approaches that may be used in the f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00254978
更新日期:1979-01-01 00:00:00
abstract::Leucovorin requirements for protection of the T cell line CCRF-CEM and the B cell line LAZ-007 against the cytotoxic effects of a variety of antifolates were studied. Differential leucovorin protection for DDMP-induced growth suppression occurred in the opposite direction to that for MTX, with CCRF-CEM requiring less ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257519
更新日期:1985-01-01 00:00:00
abstract::The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tum...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s002800050699
更新日期:1997-01-01 00:00:00
abstract::The present study deals with the influence of some bis(eta 5-cyclopentadienyl)titanium(IV) (titanocene) complexes, mainly represented by titanocene dichloride, on the development of several human gastrointestinal (GI) carcinomas (one stomach, seven colon, four sigmoid, and two rectal adenocarcinomas), all xenografted ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00451646
更新日期:1989-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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abstract::Nanoparticulate carriers of anthracyclines are being developed with the aim of improving the pharmacokinetic or pharmacodynamic behavior of these drugs. To understand how the drug reaches its nuclear targets, we have developed two methods that allow the quantification of the interaction between an anthracycline and ce...
journal_title:Cancer chemotherapy and pharmacology
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更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Oxaliplatin (OHP) in combination with 5-fluorouracil/leucovorin (FOLFOX) is clinically used as frontline therapy in patients with advanced colorectal carcinoma (CRC), with response rates ranging from 46 to 71%. This combination is now considered a standard treatment for metastatic CRC and also in the post-opera...
journal_title:Cancer chemotherapy and pharmacology
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更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. METHODS:Part 1 used an open-label, two-...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-017-3471-x
更新日期:2017-12-01 00:00:00
abstract::To obtain a clearer definition of the relationship between the structure of BCNU and CCNU and their antitumor activity, we determined the uptake, distribution, and tissue/plasma partition ratios of both compounds in normal organs and intracerebral (ic) 9L tumors in rats. Greater uptake, distribution, and tissue/plasma...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/BF00257156
更新日期:1978-01-01 00:00:00
abstract::A total of 37 men with epidermoid head and neck cancer whose disease had recurred following primary treatment (surgery and/or radiotherapy) received first-line chemotherapy with ifosfamide at i.v. doses of 3 g/m2 given daily on 3 consecutive days in combination with mesna (600 mg/m2 x 3 oral daily doses on days 1-3) e...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1993-01-01 00:00:00
abstract:PURPOSE:The study investigated the effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells. METHODS:Six human colorectal cancer cells were exposed to pemetrexed, gefitinib, and their combination. Antitumor effects were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium br...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-013-2251-5
更新日期:2013-10-01 00:00:00
abstract:PURPOSE:Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients. METHODS:Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were...
journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-010-1485-8
更新日期:2011-08-01 00:00:00
abstract:PURPOSE:Dinaciclib inhibits cyclin-dependent kinases 1, 2, 5, and 9 with a better therapeutic index than flavopiridol in preclinical studies. This study assessed the activity of dinaciclib in acute leukemia both in the clinic and in vitro. METHODS:Adults with relapsed/refractory acute myeloid leukemia (n = 14) and acu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2013-10-01 00:00:00
abstract:PURPOSE:Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetr...
journal_title:Cancer chemotherapy and pharmacology
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abstract::While N-phosphonacetyl-L-aspartic acid (PALA), an inhibitor of de novo pyrimidine biosynthesis, demonstrated a unique spectrum of activity during preclinical drug evaluation, multiple clinical trials have shown it to possess minimal clinical activity. One explanation for the disappointing results is the possibility th...
journal_title:Cancer chemotherapy and pharmacology
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2002-04-01 00:00:00
abstract::Treosulfan (L-threitol 1,4-bismethanesulfonate, Ovastat) is an alkylating agent and a structural analogue of busulfan. It has been established in the clinical chemotherapy of human ovarian carcinomas for several years and has additionally been shown to be effective against xenografted human breast carcinomas. No other...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00688319
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:To characterize cobimetinib pharmacokinetics and evaluate impact of clinically relevant covariates on cobimetinib pharmacokinetics. METHODS:Plasma samples (N = 4886) were collected from 487 patients with various solid tumors (mainly melanoma) in three clinical studies (MEK4592g, NO25395, GO28141). Cobimetinib ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2862-0
更新日期:2015-11-01 00:00:00
abstract:PURPOSE:To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. METHODS:The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m(2) on day 1 plus leucovorin (LV) 400 mg/m(2) on day 1 plus 5-fluorouracil (5-FU...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00253241
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The aim of the present study was to develop a new strategy for combined thermo-chemotherapy of cancer. For this purpose, we used ultrasound waves [1 MHz; 1 W/cm2; 10 min] in combination with a sonosensitizing nanoplatform, named ACA, made of alginate co-loaded with cisplatin and gold nanoparticles (AuNPs). MET...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03961-9
更新日期:2019-12-01 00:00:00
abstract::Trastuzumab has deeply and radically changed the course of HER2-positive breast cancer disease. The recent development of a subcutaneous (SC) formulation of trastuzumab is an important step towards improved patients' care. SC trastuzumab at a fixed dose of 600 mg administered every 3 weeks for about 5 min provides a v...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2013-12-01 00:00:00
abstract:PURPOSE:The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. METHODS:International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased af...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1249-5
更新日期:2010-10-01 00:00:00
abstract::The cytotoxicity of cisplatin alone and in combination with topotecan (TPT) or SN-38, two novel topoisomerase I (topo I) inhibitors, was determined in a panel of eight well-characterized human solid-tumor cell lines. Interactions between cisplatin and these topo I inhibitors were investigated using three different adm...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050744
更新日期:1998-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04201-1
更新日期:2021-01-01 00:00:00
abstract::Exposure of cells of the K-562 erythroleukemia cell line to 4-hydroperoxycyclophosphamide (4-HC), an analog of activated cyclophosphamide, causes a concentration-dependent inhibition of in vitro colony formation by these cells. For investigation of the role of glutathione (GSH) in the metabolism of 4-HC, GSH levels of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02994088
更新日期:1990-01-01 00:00:00