Abstract:
:Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2 h. Treatments with 200 ng/ml cisplatin or 400 ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400, respectively) that showed low level (approximately two-fold) resistance after eight treatments. Treatments with 1,000 ng/ml cisplatin or 2,000 ng/ml oxaliplatin for 2 h also produced sublines, however, these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that 'regrowth resistance' initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulphoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggesting that the taxanes may be useful in the treatment of platinum-resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Stordal BK,Davey MW,Davey RAdoi
10.1007/s00280-005-0148-7keywords:
subject
Has Abstractpub_date
2006-08-01 00:00:00pages
256-65issue
2eissn
0344-5704issn
1432-0843journal_volume
58pub_type
杂志文章abstract:PURPOSE:The relationships between pharmacokinetic parameters of unchanged cisplatin (CDDP) and several markers for nephrotoxicity after CDDP infusion (80 mg/m2) over 2 and 4 h were quantitated in patients with various cancers (lung, stomach and colon cancers and mediastinal tumor). METHODS:Plasma and urinary levels of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050548
更新日期:1996-01-01 00:00:00
abstract::All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the J...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s002800100308
更新日期:2001-08-01 00:00:00
abstract::The study under discussion was a drug-drug interaction study in which the effect of ketoconazole, a potent CYP450 3A4 inhibitor, on the pharmacokinetics of Glivec (imatinib) was investigated. A total of 14 healthy subjects (13 male, 1 female) were enrolled in this study. Each subject received a single oral dose of ima...
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/s00280-004-0832-z
更新日期:2004-10-01 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::Anticipating the renewed clinical trial of the antitumor agent 2-amino-1,3,4-thiadiazole (AT, NSC-4728), we have studied the pharmacologic fate of AT-5-14C in beagle dogs. The drug was only minimally metabolized in 5 h; the radioactivities in the urine, and particularly in the plasma, resided almost entirely in unchan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255274
更新日期:1980-01-01 00:00:00
abstract::Erratum to: Cancer Chemother Pharmacol (2014), 74:1139–1147, DOI 10.1007/s00280‑014‑2586‑6. Unfortunately, the part of acknowledgement detail was omitted in the published article and the below line must be considered as the last sentence: "This study is a Turkish Oncology Group trial". ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 已发布勘误
doi:10.1007/s00280-015-2797-5
更新日期:2015-07-01 00:00:00
abstract::The ability of the polysulfonated antitumor drug suramin and six related polysulfonated azo dyes to inhibit the cell growth, platelet-derived growth factor (PDGF)-receptor binding, and intracellular Ca2+ signaling of Swiss 3T3 fibroblasts was studied. Some of the azo dyes were more potent inhibitors of PDGF binding th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685552
更新日期:1992-01-01 00:00:00
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
doi:10.1007/s00280-009-1114-6
更新日期:2010-05-01 00:00:00
abstract:PURPOSE:In the treatment of head and neck malignancy, cisplatin and 5-FU have been used the most as chemotherapeutic agents. The difference in efficacies of these is unclear and controversial. To investigate more effective schedule, we analyzed the cytotoxicity in different treatment sequence with two agents in vitro a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0658-6
更新日期:2008-10-01 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: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::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:OBJECTIVE:SDX-101 is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac, and has anti-tumour activity in chronic lymphocytic leukaemia (CLL). SDX-308 and SDX-309 are more potent, structurally related indole-pyran analogues of SDX-101. The current study was performed to i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0400-9
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:This study characterized the pharmacokinetics, mass balance, routes and extent of elimination, metabolites, and safety of a single oral dose of (14)C-linsitinib, an IGF-1R/IR inhibitor, in patients with advanced solid tumors. The tolerability of linsitinib after multiple-dose administration was assessed in thos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-2999-5
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:To evaluate the population pharmacokinetics of pemetrexed disodium in cancer patients enrolled in four different open-label, multicenter, nonrandomized phase II studies. METHODS:Pemetrexed disodium was administered as a 10-min intravenous infusion (600 mg/m2) every 21 days. A total of four blood samples were t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000144
更新日期:2000-01-01 00:00:00
abstract::Ankinomycin is a new antitumor antibiotic found in the culture broth of Streptomyces sp. SF2587. Ankinomycin showed marked cytotoxicity and antitumor activity against some murine leukemias, but the activity against murine solid tumors was rather weak because of its strong acute toxicity. We synthesized ankinomycin acy...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685831
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:Hemolytic anemia has been noted during treatment with a variety of chemotherapeutic agents. We observed mild compensated hemolytic anemia in a patient receiving capecitabine during a randomized, controlled trial of adjuvant therapy. In order to investigate the hypothesis that hemolysis is the underlying caus...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-005-1011-6
更新日期:2005-12-01 00:00:00
abstract::Unfortunately, the online published article has error in Figure 4. The correct Figure 4 is given here. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00280-018-3590-z
更新日期:2018-06-01 00:00:00
abstract:PURPOSE:Long-term hormonal ablation in prostate cancer is associated with decreased overall health and quality of life. Few reports emphasized the role of chemotherapy in the management of early stage prostate cancer. This study analyzed the safety and efficacy of androgen deprivation therapy (ADT) plus chemotherapy as...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2163-4
更新日期:2013-06-01 00:00:00
abstract:PURPOSE:Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral rubitecan administered in a daily times five schedule. METHODS:Concentration-time data of rubitecan and 9-A...
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/s00280-002-0516-5
更新日期:2002-12-01 00:00:00
abstract::The cytotoxic action of two morpholino anthracyclines, methoxymorpholino anthracycline (MRA-MT, FCE 23,762) and cyanomorpholino anthracycline (MRA-CN), was compared with the cytotoxicity of doxorubicin (DOX), the topoisomerase II inhibitor etoposide (VP-16), the topoisomerase I inhibitor camptothecin, methotrexate, an...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689457
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:It has recently been recognised that anticancer chemotherapy can elicit an immunogenic form of apoptosis characterised by the exposure of calreticulin (CRT) on the surface of dying tumour cells, entailing an immune response that contributes to the therapeutic outcome. CRT exposure has been found to be induced b...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1302-4
更新日期:2010-08-01 00:00:00
abstract::The intestinal absorption of 6-mercaptopurine and its nucleoside 6-mercaptopurine riboside has been studied in the rat with the in situ dual luminal and vascular perfusion. 6-Mercaptopurine is an inactive prodrug that requires intestinal absorption, cellular uptake and intracellular anabolism for cytotoxic activity. V...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689198
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial. METHODS:In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050811
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:STAT3 overexpression has been detected in several cancers including head and neck squamous cell carcinoma (HNSCC). Previous studies using intratumoral administration of a STAT3 decoy oligonucleotide that abrogates STAT3-mediated gene transcription in preclinical cancer models have demonstrated antitumor effi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0823-6
更新日期:2009-05-01 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: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
doi:10.1007/s00280-016-2982-1
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS:To test the hypothesis that MGMT deficiency was required for an al...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3700-y
更新日期:2019-01-01 00:00:00
abstract::We have previously demonstrated that overexpression of dihydrodiol dehydrogenase isoform 1 (DDH1) or DDH2 leads to the induction of drug resistance to platinum based drugs in human ovarian, lung, cervical and germ cell tumor cell lines. DDH belongs to a family of aldoketo reductases that are involved in the detoxifica...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0554-0
更新日期:2008-05-01 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