Abstract:
PURPOSE:As a follow-up to our previous findings that platinum drugs induce a key enzyme in polyamine catabolism, gene expression profiling and mathematical modeling were used to define the effects of cisplatin and oxaliplatin on the expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma cells. METHODS:Time-course and concentration-effect experiments were each carried out with cisplatin or oxaliplatin in two separate experiments and cells subjected to gene expression profiling using Affymetrix array technology. Time-course data were modeled using exponential increase and decrease models. Concentration-effect data were modeled using a four parameter Hill model. RESULTS:Gene expression profiling of human ovarian carcinoma A2780 cells after exposure to either cisplatin or oxaliplatin indicates that the expression of several genes involved in polyamine pathway is affected by the platinum drugs. Mathematical/Statistical modeling of the data from time-course and concentration-effect experiments of gene expression from nine polyamine pathway genes represented on the HGU95Av2 chip, indicates that three biosynthetic pathway genes (SAMDC, ODC1 and SRM) are down-regulated and one catabolic pathway gene (SSAT) is up-regulated. Expression changes were similar for different probesets for a given gene on the array. Studies on the induction of SSAT by platinum drugs suggested by the Affymetrix data have been previously validated from this laboratory (Hector et al. in Mol Cancer Ther 3:813-822, 2004). Here, the effects of oxaliplatin exposure on SAMDC and ODC observed by Affymetix are validated with real time QRT-PCR. CONCLUSION:The data indicate a concerted effect of platinum drugs on the polyamine metabolic pathway with down-regulation in the expression of several enzyme genes involved in biosynthesis and many-fold up-regulation in expression of SSAT, an acetylating enzyme gene that is critically involved in polyamine catabolism and export.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Varma R,Hector S,Greco WR,Clark K,Hawthorn L,Porter C,Pendyala Ldoi
10.1007/s00280-006-0325-3subject
Has Abstractpub_date
2007-05-01 00:00:00pages
711-23issue
6eissn
0344-5704issn
1432-0843journal_volume
59pub_type
杂志文章abstract:PURPOSE:To assess the translational value of anticancer preclinical models, we retrospectively investigated the relationships between preclinical data and clinical response rate for 42 small-molecule targeted anticancer drugs approved by the US FDA from 2001 to 2018. METHODS:For 42 FDA-approved drugs, relevant pre-cli...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-020-04076-2
更新日期:2020-06-01 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:BACKGROUND:Very little is known about the pharmacokinetics of chemotherapeutic agents in patients also being treated with continuous ambulatory peritoneal dialysis. We sought to evaluate the pharmacokinetics of cisplatin and 5-fluorouracil in plasma and peritoneal dialysate in a patient being treated for esophageal ade...
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doi:10.1007/s00280-015-2939-9
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abstract::The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the poten...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-018-3541-8
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:Docetaxel has marked inter-patient PK variability, and metabolic phenotypic probes may enable individualised dosing. This is the first report directly comparing the erythromycin breath test (EBT) (a CYP3A4 probe) with the antipyrine clearance test (ACT), (a general CYP-P450/predominant CYP3A4 probe) for the ...
journal_title:Cancer chemotherapy and pharmacology
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更新日期:2012-01-01 00:00:00
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
doi:10.1007/s002800100354
更新日期:2001-11-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
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更新日期:2009-03-01 00:00:00
abstract:PURPOSE:To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory breast carcinoma. PATIENTS AND METHODS:A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center by a combined-modality ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050664
更新日期:1997-01-01 00:00:00
abstract::Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is effective against several tumor systems in vitro and in vivo. V79 cells that were 125- to 250-fold resistant to bizelesin developed after constant exposure to gradually increasing concentrations of the drug. Resistant cells exhibited a multi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686110
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are needed, especially in patients with human papilloma virus (HPV)-negative disease who have worse outcomes despite multimodality therapy. METHODS:Using our institutional review board ap...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2584-8
更新日期:2014-11-01 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:We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0621-6
更新日期:2008-08-01 00:00:00
abstract:PURPOSE:Standardized enumeration of CEC counts is required to minimize variability and allow cross-studies comparisons. The purpose of this paper is to identify CEC threshold proposal, by CellSearch system, for determining response to bevacizumab-based chemotherapy in metastatic colorectal cancer. METHODS:From July 20...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1543-2
更新日期:2011-09-01 00:00:00
abstract:PURPOSE:Patupilone (EPO906) is a novel potent microtubule stabilizer, which has been evaluated for cancer treatment. A novel physiologically based pharmacokinetics (PBPK) model was developed based on nonclinical data to predict the disposition of patupilone in cancer patients. METHODS:After a single intravenous dose (...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1863-5
更新日期:2012-06-01 00:00:00
abstract:PURPOSE:Gemcitabine/cisplatin combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). We aimed to evaluate the efficacy and safety of adding S-1 to gemcitabine/cisplatin combination therapy for patients with advanced BTC. METHODS:Patients with histologic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-014-2648-9
更新日期:2015-02-01 00:00:00
abstract:PURPOSE:The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. METHODS:Six female non-heart-fa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800051005
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone. METHODS:I...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3141-4
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1447-1
更新日期:2010-11-01 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
pub_type: 杂志文章
doi:10.1007/s00280-010-1485-8
更新日期:2011-08-01 00:00:00
abstract:PURPOSE:Many patients with non-small cell lung cancer (NSCLC) are eligible only for palliative radiation (RT) at presentation. This study was designed to assess the feasibility of adding the anti-EGFR monoclonal antibody nimotuzumab to palliative thoracic RT. METHODS:Patients with stage IIB, III or IV NSCLC considered...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1379-9
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resis...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2018-11-01 00:00:00
abstract:PURPOSE:Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However, no standard treatment regimens have been established. This phase II study was designed to evaluate the efficacy and safety of a paclitaxel, cisplatin and 5-FU combination in metastatic and/...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-2020-x
更新日期:2013-02-01 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::Pretreatment of the human lymphoblastoid cell line CCRF-CEM with 0.02 microM arabinosyl cytosine (ara C) enhances both the cytotoxic and the DNA-damaging effects of etoposide. This concentration of ara C is itself non-cytotoxic and results in no detectable DNA damage as measured by alkaline elution. Ara C pretreatment...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685101
更新日期:1992-01-01 00:00:00
abstract::The technique of alkaline elution was employed to study the interactions of methylene dimethane sulphonate (MDMS) and formaldehyde (HCHO) with DNA from Yoshida lymphosarcoma cells treated with these agents. MDMS and HCHO produced a proteinase sensitive filter retention which indicated the presence of DNA-protein cross...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00296247
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:Seviteronel is an orally-administered selective cytochrome P450c17a 17,20-lyase and androgen receptor inhibitor with anti-tumor activity in vitro and in vivo, and clinical activity in men with advanced castration-resistant prostate cancer (CRPC) and men and women with advanced breast cancer. The purpose of this...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03908-0
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:In gemcitabine-pretreated pancreatic cancer, salvage chemotherapy has not been established, and the prognostic factors are not completely known. The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) in patients with gemcitabin...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-011-1584-1
更新日期:2011-10-01 00:00:00
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
doi:10.1007/s002800050528
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:Triple-negative breast cancers (TNBCs) do not derive benefit from molecular-targeted treatments such as endocrine therapy or anti-HER2 therapy because they lack those molecular targets. On the other hand, TNBCs have been shown to respond to neoadjuvant chemotherapy (NAC). In this study, we analyzed TNBC patient...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1371-4
更新日期:2011-04-01 00:00:00
abstract::The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258113
更新日期:1985-01-01 00:00:00