ArticleGene therapy2010
Chemoprotection of human hematopoietic stem cells by simultaneous lentiviral overexpression of multidrug resistance 1 and O(6)-methylguanine-DNA methyltransferase(P140K).
Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cells in patients undergoing transplantation for AIDS-related lymphoma.Science translational medicine · 2010Trial
- Brain Tumors: Development, Drug Resistance, and Sensitization - An Epigenetic Approach.Epigenetics · 2023Review
- Amygdalin as a chemoprotective agent in co-treatment with cisplatin.Frontiers in pharmacology · 2022Article
- Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?International journal of molecular sciences · 2021Review
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- Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017Review
- Article
- Chemoprotection of murine hematopoietic cells by combined gene transfer of cytidine deaminase (CDD) and multidrug resistance 1 gene (MDR1).Journal of experimental & clinical cancer research : CR · 2015Article
- Gene therapy in pancreatic cancer.World journal of gastroenterology · 2014Review
- Drug resistance in cancer: an overview.Cancers · 2014Review
- Gene therapy for cancer: present status and future perspective.Molecular and cellular therapies · 2014Review
- CXCR4 Expression and Treatment with SDF-1α or Plerixafor Modulate Proliferation and Chemosensitivity of Colon Cancer Cells.Translational oncology · 2013Article
- Combinatorial RNA-based gene therapy for the treatment of HIV/AIDS.Expert opinion on biological therapy · 2013Review
- F2A sequence linking MGMT(P140K) and MDR1 in a bicistronic lentiviral vector enables efficient chemoprotection of haematopoietic stem cells.Cancer gene therapy · 2012Article
- Cooperative cluster formation, DNA bending and base-flipping by O6-alkylguanine-DNA alkyltransferase.Nucleic acids research · 2012Article
- Treatment of a solid tumor using engineered drug-resistant immunocompetent cells and cytotoxic chemotherapy.Human gene therapy · 2012Article
- Impact of temozolomide on immune response during malignant glioma chemotherapy.Clinical & developmental immunology · 2012Review
- Current progress and challenges in HIV gene therapy.Future virology · 2011Article
- Targeting O⁶-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy.Cellular and molecular life sciences : CMLS · 2010Review
- Computational models of HIV-1 resistance to gene therapy elucidate therapy design principles.PLoS computational biology · 2010Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myelotoxicity is a dose-limiting effect of many chemotherapeutic regimens. Thus, there is great interest in protecting human hematopoietic stem cells by the transfer of drug resistance genes. The main focus of this study was the simultaneous overexpression of multidrug resistance 1 (MDR1) and the O(6)-benzylguanine (O(6)-BG)-resistant mutant MGMT(P140K) (O(6)-methylguanine-DNA methyltransferase) with a bicistronic lentiviral vector (HR'SIN-MDR1-IRES-MGMT(P140K)), with regard to the capability to convey chemoprotection in the leukemia cell line, HL60, and human hematopoietic stem cells (CD34(+)). Combination therapy with O(6)-BG/1-(2-chloroethyl)-3-(4-amino-2-methylpyrimidine-5-yl)methyl-1-nitrosourea) (ACNU) plus paclitaxel showed a significant survival advantage of HL60 cells transduced with this combination vector. In CD34(+) cells, monotherapy with O(6)-BG/temozolomide (TMZ) resulted in an increased percentage of MGMT-positive cells (vs untreated cells) after transduction with HR'SIN-MDR1-IRES-MGMT(P140K) (28.3%). For combination therapy with O(6)-BG/temozolomide plus paclitaxel the increase was higher with the combination vector (52.8%) than with a vector expressing MGMT(P140K) solely (29.1%). With regard to MDR1-positive cells the protective effect of the combination vector (88.5%) was comparable to the single vector HR'SIN-MDR1 (90.0%) for monotherapy with paclitaxel and superior for combination therapy with O(6)-BG/temozolomide plus paclitaxel (84.6 vs 69.7%). In conclusion, the combination vector presents simultaneous protective effects of two drug-resistance genes, offering an opportunity to increase the cancer therapeutic index.
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