Abstract:
PURPOSE:There is considerable current interest in the use of thalidomide as a single agent or in combination with drugs such as cyclophosphamide in the treatment of multiple myeloma and other cancers. Our previous work has shown that thalidomide potentiates the antitumour activity of both cyclophosphamide and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against murine Colon 38 tumours. In both of these cases, thalidomide extends the half-life (t(1/2)) of the other drug. We wished to determine whether cyclophosphamide and DMXAA altered the t(1/2) of thalidomide. Since both thalidomide and DMXAA modulate tumour necrosis factor (TNF), we also wished to determine the role of TNF in this interaction. METHODS:Mice with Colon 38 tumours were treated with cyclophosphamide (220 mg/kg) and/or thalidomide (20 mg/kg) or DMXAA (25 mg/kg) and thalidomide (100 mg/kg), combinations that have previously demonstrated synergistic activity. Plasma and tumour tissue drug concentrations were analysed by high-performance liquid chromatography. To determine the role of TNF, similar experiments were performed using mice defective in the TNF gene (TNF(-/-)) or the TNF receptor-1 gene (TNFR1(-/-)). RESULTS:Coadministration of cyclophosphamide increased the thalidomide t(1/2) by 3.9- and 3.6-fold, respectively, in plasma and tumour tissue, with a corresponding increase in the concentration-time curve (AUC). The corresponding values following coadministration of DMXAA were 3.0- and 4.6-fold, respectively. Coadministration of cyclophosphamide had similar effects on thalidomide t(1/2) in C57Bl/6, TNF(-/-) and TNFR1(-/-) mice, while coadministration of DMXAA did not alter the t(1/2) or AUC in TNF(-/-) and TNFR1(-/-) mice. CONCLUSIONS:Both cyclophosphamide and DMXAA have a pharmacokinetic interaction with thalidomide, increasing t(1/2) and AUC. TNF mediates the effect of DMXAA on thalidomide pharmacokinetics but not that of cyclophosphamide.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Chung F,Wang LC,Kestell P,Baguley BC,Ching LMdoi
10.1007/s00280-003-0753-2keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
377-83issue
5eissn
0344-5704issn
1432-0843journal_volume
53pub_type
杂志文章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
pub_type: 杂志文章
doi:10.1007/s00280-013-2251-5
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:Expression of the DNA repair protein O (6)-methylguanine-DNA methyltransferase (MGMT) correlates with resistance to irinotecan in colorectal cancer cell lines. This phase I study evaluated the maximum tolerated dose (MTD) of lomeguatrib, an inactivating pseudosubstrate of MGMT, in combination with irinotecan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1225-0
更新日期:2010-10-01 00:00:00
abstract::The full-scale commercial appearance of antibiotics in the 1950s caused a shift in the nature of lethal diseases from infectious and acute to noninfectious and chronic. In this situation, biological response modifiers (BRMs), which are not based on selective toxicity, could be expected to be useful. Several types of B...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-003-0590-3
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:To investigate the activity of combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin in patients with metastatic urothelial cancer. METHODS:A group of 29 patients were treated with 2000 mg/m2 ifosfamide, 750 mg/m2 5-fluorouracil, 100 mg/m2 etoposide and 20 mg/m2 cisplatin. All four ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100320
更新日期:2001-07-01 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::The effect of acetazolamide (A.A.) on the antineoplastic activity of 1-phthalidyl 5-fluorouracil (PH-FU) against rat and mouse solid tumors was examined. A.A., an inhibitor of liver PH-FU hydrolase, had no antitumor activity but greatly enhanced the activity of PH-FU when coadministered. The potentiation was evaluated...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255286
更新日期:1986-01-01 00:00:00
abstract::Activation of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on T cells leads to T cell exhaustion and ultimately facilitates tumor progression. Recent success of using immune cell checkpoint inhibitors offers a great promise to treat various cancers, including bladder cancer. However, the exp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03800-x
更新日期:2019-05-01 00:00:00
abstract::Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689272
更新日期:1990-01-01 00:00:00
abstract::The mechanism of toxicity of 3-deazaguanosine was studied in a number of human tumor cell lines by determination of the effects of various purine compounds on the growth of the cells in the presence of the drug and by studies of the effects of 3-deazaguanosine on the metabolism of radiolabeled precursors in these cell...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257296
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:Imatinib is an inhibitor of the Bcr-Abl tyrosine kinase; however, resistance is common. Flavopiridol, a cyclin-dependent kinase (CDK) inhibitor, down-regulates short-lived anti-apoptotic proteins via inhibition of transcription. In preclinical studies, flavopiridol synergizes with imatinib to induce apoptosis. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1839-5
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686275
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-011-1748-z
更新日期:2011-12-01 00:00:00
abstract::The in vitro effect of the dextroisomer r-verapamil on blast cells derived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferation in the presence of stem-cell factor, leukemia inhibitory factor, interleukin 4, interleukin 6, and interl...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685631
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Multi-drug resistance and cumulative cardiotoxicity are major limitations for the clinical use of anthracyclines. Here, we evaluated and compared the cross-resistance of amrubicin, a third-generation synthetic anthracycline and potent topoisomerase (topo)-II inhibitor with little or no observed cardiotoxicity t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1782-x
更新日期:2012-04-01 00:00:00
abstract::We used a microdialysis technique to determine tissue methotrexate (MTX) levels during steady state in a rodent model. Two different approaches were employed to measure the actual extracellular MTX concentrations in muscle, liver, and kidney tissues of anesthetized Wistar rats. With the reduced-perfusion-rate techniqu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050403
更新日期:1996-01-01 00:00:00
abstract::Cultures of human colon carcinoma, HCT-8, were treated with millimolar concentrations of thymidine by different schedules designed to cytokinetically and biochemically modulate methotrexate (MTX) and 5-fluorouracil (FUra) toxicity. Thymidine (dThd)-synchronized HCT-8 cells monitored by flow cytofluorometry showed incr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254600
更新日期:1984-01-01 00:00:00
abstract::A combination of carboplatin, vincristine, methotrexate and bleomycin (COMB) was given to 29 patients with locally advanced, metastatic or recurrent cervical carcinoma. A total of 85 cycles of chemotherapy were given, with half of the patients receiving greater than 3 cycles. Both the response rate (32.1%) and the med...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685165
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0933-9
更新日期:2009-09-01 00:00:00
abstract::Anthracyclines are important antitumor agents used in the treatment of solid tumors, lymphomas, and acute lymphoblastic as well as myelocytic leukemias. The clinical utility of agents such as doxorubicin and daunorubicin and their well-characterized cardiotoxicity have prompted many efforts to develop analogs that ret...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686485
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Midostaurin (PKC412) is a multitargeted tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 receptor (FLT3), c-KIT, and other receptors. Midostaurin is active in patients with acute myeloid leukemia and systemic mastocytosis. Although no substantive risk for cardiac abnormalities has been observed with mido...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-012-1825-y
更新日期:2012-05-01 00:00:00
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
doi:10.1007/BF00269032
更新日期:1984-01-01 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::The intra-cellular uptake of the weakly basic radiosensitiser pimonidazole (PIMO) was determined as a function of the pigmentation of Na11+ human melanotic melanoma cells in vitro. Two experimental conditions were considered: exponentially growing cells (Exp.) and plateau-phase cells (PI.). The melanin content of Na11...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685671
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:The study mainly aimed to determine the biological function of a novelly synthesized phenanthroimidazole derivative, named L233, and to explore its potential mechanisms. METHODS:Cell survival was examined using the MTT assays, and the DNA-damaging role of L233 was explored using the comet assay. Moreover, the ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2894-5
更新日期:2016-01-01 00:00:00
abstract::Tumor-tissue and plasma concentrations of platinum were studied prospectively in two groups of eight patients who were suffering from advanced non-small-cell lung cancer. Treatments including two different schedules of cisplatin administration (25 vs 100 mg/m2 on day 1) were compared. At 30 min after the beginning of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689280
更新日期:1990-01-01 00:00:00
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 cel...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0333-3
更新日期:2007-05-01 00:00:00
abstract:PURPOSE:Chemotherapy dosing in neonates represents a major clinical challenge because of a lack of clinical pharmacology information in this patient population. In this study, we investigate the use of cisplatin dose adaptation based on therapeutic drug monitoring in a 2-week-old neonate with localized hepatoblastoma. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3625-5
更新日期:2018-08-01 00:00:00
abstract:PURPOSE:To investigate the effect of the antihistamine ketotifen on multidrug resistance in human breast cancer cells and doxorubicin toxicity in mice. METHODS:Clonogenicity assays were used to test the effect of ketotifen on human multidrug resistant breast cancer cell lines exposed to chemotherapeutic agents. Flow c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0600-5
更新日期:2003-05-01 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:PURPOSE:Low-dose methotrexate (MTX) therapy is the cornerstone treatment of acute lymphoblastic leukemia (ALL) and may enhance the activation of 6-mercaptopurine (6-MP) to 6-thioguanine nucleotides (6-TGN). Yet, data have established that high-dose MTX (HDMTX) hampers the accumulation of 6-TGN in red blood cells (RBC) ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1205-4
更新日期:2010-09-01 00:00:00