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 this pathway and how this may be related to the development of resistance was also investigated. METHODS:Mitochondrial membrane potential and ROS analysis were performed by flow cytometry, P-JNK and P-p38 by western blotting and mRNA by RT-PCR. Dihydrodiol dehydrogenase (DDH1) and thioredoxin knockdowns were prepared by standard techniques. RESULTS:Cisplatin treatment of a cervical cancer cell line resulted in ROS production with mitochondrial membrane depolarization and phosphorylation of JNK and p38. N-acetyl-cysteine, a free radical scavenger, ameliorated these effects. Treatment of the sensitive cells with H2O2 produced similar effects but at shorter incubation times. Similar results were observed with an ovarian cell line. Downregulation of dihydrodiol dehydrogenase in the cisplatin-resistant cervical and lung cancer cell lines resulted in increased drug sensitivity with detectable production of ROS and activation of the JNK/p38 pathways; however, downregulation of thioredoxin in the cervical cells had minimal effect. CONCLUSION:Dihydrodiol dehydrogenase appears to play a role in cisplatin resistance in cervical, ovarian and lung cancer cells which includes mitochondrial membrane depolarization, ROS production and activation of the JNK pathway. However, its mode of action cannot be mimicked by an ROS scavenger so its mechanism of action is more complex (a not unexpected finding considering its role in xenobiotic activation/countering oxidative stress).
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Chen J,Solomides C,Parekh H,Simpkins F,Simpkins Hdoi
10.1007/s00280-015-2739-2subject
Has Abstractpub_date
2015-06-01 00:00:00pages
1217-27issue
6eissn
0344-5704issn
1432-0843journal_volume
75pub_type
杂志文章abstract:PURPOSE:In vitro and in vivo preclinical models have demonstrated synergistic activity when topoisomerase I and II inhibitors are administered sequentially. Topoisomerase I inhibitors increase topoisomerase II levels and increase cell kill induced by topoisomerase II poisons. We evaluated this hypothesis in a cohort of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800000211
更新日期:2001-01-01 00:00:00
abstract::A 44-year-old man who had achieved a complete remission of malignant peritoneal mesothelioma after the intraperitoneal administration of 25 mg/m2 mitoxantrone presented with clinical and radiological signs of intestinal obstruction suggestive of recurrent disease at about 2 years following the initial treatment. Howev...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686012
更新日期:1992-01-01 00:00:00
abstract::Experimental evidence indicates that the anthracycline antibiotic doxorubicin (adriamycin) localizes mainly in cell nuclei of cardiac cells and has a high affinity to several cellular constituents in addition to DNA. In the present study the cellular kinetics of doxorubicin in cultured rat myocardial cells were determ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256692
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:The interindividual variability of vincristine pharmacokinetics is quite large, but the origins of this variability are not properly understood. The aim of this study was to develop a population pharmacokinetic model of vincristine in a paediatric population treated for solid tumour disease and evaluate the imp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1541-4
更新日期:2011-11-01 00:00:00
abstract:PURPOSE:Afatinib is an irreversible ErbB family blocker currently under evaluation in late-stage clinical trials. This study primarily assessed the cardiac safety, pharmacokinetics and antitumor activity of afatinib in cancer patients. METHODS:In this multicenter, Phase II, open-label, single-arm trial, 60 patients wi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-013-2286-7
更新日期:2013-12-01 00:00:00
abstract::Plasmatic and salivary concentrations of 5-FU were investigated in ten patients given 5-day continuous infusions of 5-fluorouracil (5-FU) (1 g/m2/day). Measurable concentrations of salivary 5-FU were scattered ranging from 6 to 100 ng/ml. Between individual 5-FU concentrations in saliva and plasma the coefficient of c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00300243
更新日期:1989-01-01 00:00:00
abstract::The toxic effect of 3'-deoxyadenosine N1-oxide (3'-dANO) on mice, on their different organs, and on Ehrlich ascites tumor cells was studied. In both healthy and tumour-bearing animals, the lethal dose for 10% of the mice receiving i.p. injections (LD10) of 3'-dANO was estimated to be about 300 mg/kg x 4 days in one mo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686398
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs. METHODS:The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from pa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1746-1
更新日期:2012-03-01 00:00:00
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 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050445
更新日期:1996-01-01 00:00:00
abstract:PURPOSE AND METHODS:MS-209 is a newly synthesized quinoline compound used orally to overcome human P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). The multidrug resistance-associated protein (MRP) gene is thought to play an important role in MDR in lung cancer. To investigate whether MS-209 could also overcom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050681
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:To characterise the pharmacokinetics and metabolism in mice of 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (SN 23862), the lead compound of a new class of bioreductive drugs in which a nitrogen mustard is activated by nitroreduction. Comparison is made with the corresponding aziridine derivative CB 195...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000165
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of the standard platinum agents, cisplatin and carboplatin, against fresh human, epithelial ovarian cancers. METHODS:The Hamburger-Salmon human tumor colony-forming assay (HTCA) was used to measure the chemosensit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050604
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Inhibitors of heat shock protein (Hsp) 90 induce apoptosis in multiple myeloma (MM) cells, but the molecular mechanisms underlying this cytotoxic outcome are not clear. Here, we investigate the effect of IPI-504, a novel and highly soluble inhibitor of the Hsp90 ATPase activity, on the unfolded protein respo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0546-0
更新日期:2008-05-01 00:00:00
abstract::Cancer is a major health issue worldwide and the global burden of cancer is expected to reduce the costs of treatment as well as prolong the survival time. One of the promising approaches is drug repurposing, because it reduces costs and shortens the production cycle of research and development. Disulfiram (DSF), whic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-020-04216-8
更新日期:2021-01-10 00:00:00
abstract:PURPOSE:We assessed the clinical efficacy and safety of mitoxantrone hydrochloride which has been used as an anticancer drug in our hospital to treat breast cancer patients since 1993. METHODS:A group of 23 patients with breast cancer were given one course of the following regimen every 3 weeks: mitoxantrone hydrochlo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0586-z
更新日期:2003-07-01 00:00:00
abstract::The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of mitomycin C (MMC), used at different concentrations, in inhibiting the growth of human gastric adenocarcinoma (AGS) cells. Combined verapamil and hyperthermia treatment resulted in a significan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685086
更新日期:1994-01-01 00:00:00
abstract:OBJECTIVES:We evaluated whether DNA repair gene polymorphisms had an effect on clinical outcomes in metastatic/recurrent nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based chemotherapy. MATERIALS AND METHODS:Clinical data of 101 patients with metastatic/recurrent NPC between 2004 and 2011 were review...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2196-8
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship bet...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04118-9
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determine...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1638-4
更新日期:2011-12-01 00:00:00
abstract::Doxifluridine (5'-deoxy-5-fluorouridine, 5'-dFUR) metabolism has been reported to be saturable and associated with a fall in clearance of the drug as the dose is increased. The aim of the present study was to determine the disposition of 5'-dFUR and 5-fluorouracil (5-FU) when 5'-dFUR was given as a 5-day infusion, wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684885
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Anti-angiogenic agents combined with histone deacetylase inhibitors act synergistically in vitro and in vivo. We conducted a phase I study of the combination of the anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers. METHODS:Bevacizumab w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2384-1
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:SU5416 is a novel small organic molecule that non-competitively inhibits the phosphorylation of the VEGF tyrosine kinase receptor, Flk-1. This phase IB study was performed to determine the safety, pharmacokinetics, and preliminary efficacy of the combination of SU5416 and paclitaxel in recurrent or metastatic c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0871-5
更新日期:2005-03-01 00:00:00
abstract:PURPOSE:Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-018-3567-y
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:This study was conducted to define the activity of irofulven in the treatment of a series of xenografts derived from human glioblastoma multiforme growing subcutaneously and intracranially in athymic nude mice. METHODS:Athymic mice bearing subcutaneous or intracranial tumors were treated with irofulven at a 10...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100358
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the efficacy and toxicities of liposome-paclitaxel and carboplatin concurrent with radiotherapy for locally advanced lung squamous cell carcinoma (LSCC). METHODS:The clinical data of 38 patients with locally advanced LSCC treated with liposome-paclitaxel based concurrent...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3640-6
更新日期:2018-09-01 00:00:00
abstract:PURPOSE:The role of the microenvironment during the initiation and progression of carcinogenesis is now realized to be of critical importance, both for enhanced understanding of fundamental cancer biology, as well as exploiting this source of relatively new knowledge for improved molecular diagnostics and therapeutics....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-008-0881-9
更新日期:2009-03-01 00:00:00
abstract::D-3-Azido-3-deoxy-myo-inositol (3AMI) is an inhibitor of the growth of v-sis-transformed NIH 3T3 cells but not of wild-type NIH 3T3 cells, whose effects may be mediated through the phosphatidylinositol-3'-kinase pathway. We studied some properties of the cellular pharmacology of 3AMI using high-specific-activity [3H]-...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686287
更新日期:1994-01-01 00:00:00
abstract::Infusion of 5'-dFUrd (2.0-3.0 g/m2 over 1 h on days 1-5 every 3rd week) resulted in one partial response in 21 patients with advanced and progressing colorectal cancer. No patient had received chemotherapy before the 5'-dFUrd trial. Hematological and gastrointestinal toxicity were generally mild. In 4 patients periphe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257528
更新日期:1985-01-01 00:00:00
abstract::Pharmacokinetic studies in 11 patients with multiple myeloma were undertaken on the first and last days of one course of chemotherapy. The drug was administered PO in single doses of 6-14 mg daily. Melphalan concentrations were determined by high-performance liquid chromatography. The interpatient variability of pharm...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00306752
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, pharmacokinetics, and pharmacodynamics of SB-743921 when administered as a 1-h infusion every 21 days to patients with advanced solid tumors or relapsed/refractory lymphoma. METHODS:Patients who failed prior standard therapy o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1346-5
更新日期:2011-02-01 00:00:00