Linked Life Data

16733832

Source:http://linkedlifedata.com/resource/pubmed/id/16733832

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-8-23
pubmed:abstractText
Tumour resistance to chemotherapeutic agents results in most chemotherapy being administered in a multi-agent fashion that is often associated with a high level of toxicity in highly proliferative tissues such as the haematopoietic compartment. Thus, whilst many genetic manipulation strategies aim to protect normal tissue against a single component of a multi-agent regime, it is clearly preferable to protect normal cells against all toxicities. In this study we have used retroviral gene transfer to achieve co-expression of either p-glycoprotein (MDR1) or multi-drug resistance-related protein 1 (MRP1) with the P140K mutant form of O6-methylguanine-DNA-methyl transferase (MGMT) which, unlike the wild-type protein, is insensitive to inactivation by tumour sensitisers such as O6-benzylguanine (O6-BeG) or PaTrin2. The combination of certain MDR1/MRP1 substrate drugs with O6-alkylating agents (against which MGMT confers resistance) is particularly myelotoxic. We show here that haematopoietic progenitors co-expressing mutant MGMT with an ABC-transporter exhibit resistance to combination chemotherapy in vitro. This combination of drug transporter and DNA repair function may provide an effective in vivo protection of the haematopoietic compartment during tumour ablation using combination chemotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1099-498X
pubmed:author
pubmed:copyrightInfo
2006 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
972-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16733832-3T3 Cells, pubmed-meshheading:16733832-Animals, pubmed-meshheading:16733832-Antineoplastic Agents, Alkylating, pubmed-meshheading:16733832-Antineoplastic Agents, Phytogenic, pubmed-meshheading:16733832-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:16733832-Carmustine, pubmed-meshheading:16733832-Drug Resistance, Multiple, pubmed-meshheading:16733832-Drug Resistance, Neoplasm, pubmed-meshheading:16733832-Etoposide, pubmed-meshheading:16733832-Gene Expression, pubmed-meshheading:16733832-Gene Transfer Techniques, pubmed-meshheading:16733832-Genes, MDR, pubmed-meshheading:16733832-Green Fluorescent Proteins, pubmed-meshheading:16733832-Hematopoietic Stem Cells, pubmed-meshheading:16733832-Humans, pubmed-meshheading:16733832-K562 Cells, pubmed-meshheading:16733832-Mice, pubmed-meshheading:16733832-Multidrug Resistance-Associated Proteins, pubmed-meshheading:16733832-Mutation, pubmed-meshheading:16733832-O(6)-Methylguanine-DNA Methyltransferase, pubmed-meshheading:16733832-P-Glycoprotein, pubmed-meshheading:16733832-Retroviridae, pubmed-meshheading:16733832-Transduction, Genetic
pubmed:year
2006
pubmed:articleTitle
Dual agent chemoprotection by retroviral co-expression of either MDR1 or MRP1 with the P140K mutant of O6-methylguanine-DNA-methyl transferase.
pubmed:affiliation
Cancer Research UK Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. Tsouthgate@picr.man.ac.uk
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't