Abstract:
PURPOSE:The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management of advanced breast cancer. METHODS:MCF-7 human breast cancer cells were transfected with gef gene using pcDNA3.1-TOPO expression vector. To determine the effect of the combined therapy, MCF-7 transfected and non-transfected cells were exposed to paclitaxel, docetaxel and doxorubicin at different concentrations. The growth-inhibitory effect of gef gene and/or drugs was assessed by MTT assay. Apoptosis modulation was determined by flow cytometric analysis, DNA fragmentation and morphological analysis. Multicellular tumour spheroids (MTS) from MCF-7 cells were used to confirm effectiveness of combined therapy (gef gene and drug). RESULTS:Our results demonstrate that combined therapy gef gene/drugs (paclitaxel, docetaxel or doxurubicin) caused a decrease in cell viability. However, only the gef-doxorubicin (10 microM) combination induced a greater enhancement in the antitumour activity in MCF-7 cells. Most importantly, this combined strategy resulted in a significant synergistic effect, thus allowing lower doses of the drug to be used to achieve the same therapeutic effect. These results were confirmed using MTS in which volume decrease with combined therapy was greater than obtained using the gene therapy or chemotherapy alone, or the sum of both therapies. CONCLUSIONS:The cytotoxic effect of gef gene in breast cancer cells enhances the chemotherapeutic effect of doxorubicin. This therapeutic approach has the potential to overcome some of the major limitations of conventional chemotherapy, and may therefore constitute a promising strategy for future applications in breast cancer therapy.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Prados J,Melguizo C,Rama AR,Ortiz R,Segura A,Boulaiz H,Vélez C,Caba O,Ramos JL,Aránega Adoi
10.1007/s00280-009-1135-1subject
Has Abstractpub_date
2010-05-01 00:00:00pages
69-78issue
1eissn
0344-5704issn
1432-0843journal_volume
66pub_type
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800051051
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer. METHODS:Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, ...
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pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1059-9
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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
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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
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doi:10.1007/s002800000165
更新日期:2000-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s002800000188
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abstract:PURPOSE:Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the ...
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doi:10.1007/s00280-005-0067-7
更新日期:2006-04-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/BF00686110
更新日期:1994-01-01 00:00:00
abstract::Intravenous (i.v.) administration of sodium thiosulfate reduces the toxicity of cis-diamminedichloroplatinum (II) (CDDP). This effect, which allows the use of increased CDDP doses, has been exploited clinically in the intraperitoneal (i.p.) treatment of intraabdominal tumors. Recently, attempts have been made to treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257358
更新日期:1988-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2018-07-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2009-03-01 00:00:00
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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
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04085-1
更新日期:2020-06-01 00:00:00
abstract::Hypocrellin compounds were selected as potential photosensitizers for photodynamic therapy (PDT) owing to their high quantum yields of singlet oxygen (1O2), and facility for site-directed chemical modification to enhance phototoxicity, pharmacokinetics, solubility, and light absorption in the red spectral region, amon...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050395
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:This dedicated QTc study was designed to evaluate the effect of the mammalian target of rapamycin inhibitor, ridaforolimus, on the QTc interval in patients with advanced malignancies. METHODS:We conducted a fixed-sequence, single-blind, placebo-controlled study. Patients (n = 23) received placebo on day 1 and ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1942-7
更新日期:2012-10-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435411
更新日期:1980-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-005-0148-7
更新日期:2006-08-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897260
更新日期:1990-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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journal_title:Cancer chemotherapy and pharmacology
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doi:10.1007/s00280-004-0798-x
更新日期:2004-08-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262782
更新日期:1988-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0416-9
更新日期:2007-10-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
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更新日期:2020-04-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0437-4
更新日期:2007-11-01 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/s00280-003-0689-6
更新日期:2004-02-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686682
更新日期:1994-01-01 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
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-2958-1
更新日期:2016-03-01 00:00:00
abstract:PURPOSE:Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular conte...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000208
更新日期:2001-03-01 00:00:00