Increasing DNA repair capacity in bone marrow by gene transfer as a prospective tool in cancer therapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92907
Title:
Increasing DNA repair capacity in bone marrow by gene transfer as a prospective tool in cancer therapy.
Authors:
Kleibl, K; Margison, Geoffrey P
Abstract:
Resistance of tumor cells to alkylating anticancer agents that produce adducts at the O6 position of guanine in DNA, the O6-alkylating agents, correlates with the expression of O6-alkylguanine-DNA alkyltransferase (ATase). O6-benzylguanine and related pseudosubstrates are able to inactivate human ATase in vitro and in vivo and they are being tested as chemotherapeutic adjuvants for enhancing the effectiveness of O6-alkylating drugs. On the other hand, the clinical consequences of ATase depletion may be fatal for some sensitive systems e.g. hematopoiesis. To overcome this problem, strategies for the protection of primary bone marrow cells by targeted transfer of pseudosubstrate-resistant ATase genes have been considered and recently achieved at the laboratory level. This approach could therefore be now extended to a clinical cancer gene therapy program.
Affiliation:
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
Citation:
Increasing DNA repair capacity in bone marrow by gene transfer as a prospective tool in cancer therapy. 1998, 45 (4):181-6 Neoplasma
Journal:
Neoplasma
Issue Date:
1998
URI:
http://hdl.handle.net/10541/92907
PubMed ID:
9890659
Type:
Article
Language:
en
ISSN:
0028-2685
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKleibl, Ken
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-02-24T14:02:55Z-
dc.date.available2010-02-24T14:02:55Z-
dc.date.issued1998-
dc.identifier.citationIncreasing DNA repair capacity in bone marrow by gene transfer as a prospective tool in cancer therapy. 1998, 45 (4):181-6 Neoplasmaen
dc.identifier.issn0028-2685-
dc.identifier.pmid9890659-
dc.identifier.urihttp://hdl.handle.net/10541/92907-
dc.description.abstractResistance of tumor cells to alkylating anticancer agents that produce adducts at the O6 position of guanine in DNA, the O6-alkylating agents, correlates with the expression of O6-alkylguanine-DNA alkyltransferase (ATase). O6-benzylguanine and related pseudosubstrates are able to inactivate human ATase in vitro and in vivo and they are being tested as chemotherapeutic adjuvants for enhancing the effectiveness of O6-alkylating drugs. On the other hand, the clinical consequences of ATase depletion may be fatal for some sensitive systems e.g. hematopoiesis. To overcome this problem, strategies for the protection of primary bone marrow cells by targeted transfer of pseudosubstrate-resistant ATase genes have been considered and recently achieved at the laboratory level. This approach could therefore be now extended to a clinical cancer gene therapy program.en
dc.language.isoenen
dc.subjectCancer Drug Resistanceen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectCancer Proteinsen
dc.subjectCanceren
dc.subject.meshAlkylation-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Line-
dc.subject.meshCricetinae-
dc.subject.meshCricetulus-
dc.subject.meshDNA Adducts-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDrug Resistance-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshGene Targeting-
dc.subject.meshGene Transfer Techniques-
dc.subject.meshGuanine-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshMice-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshNeoplasms-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshSequence Alignment-
dc.subject.meshSequence Homology, Amino Acid-
dc.titleIncreasing DNA repair capacity in bone marrow by gene transfer as a prospective tool in cancer therapy.en
dc.typeArticleen
dc.contributor.departmentCancer Research Institute, Slovak Academy of Sciences, Bratislava.en
dc.identifier.journalNeoplasmaen

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