2.50
Hdl Handle:
http://hdl.handle.net/10541/86686
Title:
Engineering drug resistance in human cells.
Authors:
Fairbairn, Leslie J; Rafferty, Joseph A; Lashford, Linda S
Abstract:
Many of the problems with current anti-tumour therapies stem from a lack of specificity for tumour as opposed to normal tissues. To address the problem of collateral toxicity during anti-tumour chemotherapy we have been developing a gene therapy approach to protect normal tissues from the toxic and potentially mutagenic effects of chemotherapeutic agents. As a paradigm for this we have been examining the potential of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) to confer genetic chemoprotection to the bone marrow. By transfer and expression of a mutant form of this protein, which is resistant to inactivation by the tumour sensitising agent O6-benzylguanine (O6-beG), we have been able to demonstrate protection of murine bone marrow in vitro from the cytotoxic and clastogenic effects of O6-beG in combination with the anti-tumour agent temozolomide. This protection is seen in multiple lineages, including erythroid and granulocyte/macrophage progenitors, as well as more primitive cells. Importantly, significant protection of the platelet lineage is also seen, with faster recovery of platelets. The multi-lineage protection seen has encouraged us to take this approach forward to clinical trial in the near future.
Affiliation:
Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
Citation:
Engineering drug resistance in human cells. 2000, 25 Suppl 2:S110-3 Bone Marrow Transplant.
Journal:
Bone Marrow Transplantation
Issue Date:
May-2000
URI:
http://hdl.handle.net/10541/86686
PubMed ID:
10933202
Type:
Article
Language:
en
ISSN:
0268-3369
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorFairbairn, Leslie Jen
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorLashford, Linda Sen
dc.date.accessioned2009-11-23T11:54:20Z-
dc.date.available2009-11-23T11:54:20Z-
dc.date.issued2000-05-
dc.identifier.citationEngineering drug resistance in human cells. 2000, 25 Suppl 2:S110-3 Bone Marrow Transplant.en
dc.identifier.issn0268-3369-
dc.identifier.pmid10933202-
dc.identifier.urihttp://hdl.handle.net/10541/86686-
dc.description.abstractMany of the problems with current anti-tumour therapies stem from a lack of specificity for tumour as opposed to normal tissues. To address the problem of collateral toxicity during anti-tumour chemotherapy we have been developing a gene therapy approach to protect normal tissues from the toxic and potentially mutagenic effects of chemotherapeutic agents. As a paradigm for this we have been examining the potential of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) to confer genetic chemoprotection to the bone marrow. By transfer and expression of a mutant form of this protein, which is resistant to inactivation by the tumour sensitising agent O6-benzylguanine (O6-beG), we have been able to demonstrate protection of murine bone marrow in vitro from the cytotoxic and clastogenic effects of O6-beG in combination with the anti-tumour agent temozolomide. This protection is seen in multiple lineages, including erythroid and granulocyte/macrophage progenitors, as well as more primitive cells. Importantly, significant protection of the platelet lineage is also seen, with faster recovery of platelets. The multi-lineage protection seen has encouraged us to take this approach forward to clinical trial in the near future.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBone Marrow-
dc.subject.meshBone Marrow Transplantation-
dc.subject.meshDNA Repair-
dc.subject.meshDrug Resistance-
dc.subject.meshFemale-
dc.subject.meshGene Therapy-
dc.subject.meshGenetic Engineering-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshNeoplasms-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.titleEngineering drug resistance in human cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalBone Marrow Transplantationen

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