Linked Life Data

12797396

Source:http://linkedlifedata.com/resource/pubmed/id/12797396

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-6-11
pubmed:abstractText
O6-alkylguanine-DNA alkyltransferase (OGAT) and the mismatch repair system (MRS) play a crucial role in the susceptibility of tumor cells to the cytotoxic effects of agents that generate O6-methylguanine in DNA, including the triazene compound temozolomide (TMZ). Studies performed with peripheral blood mononuclear cells (MNC) showed that TMZ was scarcely active on lymphocyte functions not dependent on cell proliferation (e.g. NK activity and cytokine-mediated induction of CD1b molecule in adherent MNC). In contrast, TMZ depressed proliferation and lymphokine activated killer (LAK) cell generation in response to IL-2. In this case, a reasonably good inverse relationship was found between OGAT levels of MNC and their susceptibility to TMZ. This study also analyzed the ratio of the toxic effect of TMZ on MNC and on tumor cells (i.e. "Tumor-Immune Function Toxicity Index", TIFTI). A particularly favorable TIFTI can be obtained when OGAT levels are extremely high in MNC and markedly low in tumor cells. This holds true for MRS-proficient neoplastic cells, but not for MRS-deficient tumors. In conclusion, strategies aimed at modulating OGAT and MRS may improve the clinical response to TMZ. However, the use of OGAT inhibitors to potentiate the antitumor activity of TMZ might result in a concomitant increase of the immunosuppressive effects of the drug, thus reducing the relative TIFTI.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1120-009X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-83
pubmed:dateRevised
2009-8-4
pubmed:meshHeading
pubmed-meshheading:12797396-Antineoplastic Agents, Alkylating, pubmed-meshheading:12797396-Burkitt Lymphoma, pubmed-meshheading:12797396-Cell Division, pubmed-meshheading:12797396-DNA Damage, pubmed-meshheading:12797396-DNA Repair, pubmed-meshheading:12797396-Dacarbazine, pubmed-meshheading:12797396-Drug Resistance, Neoplasm, pubmed-meshheading:12797396-Humans, pubmed-meshheading:12797396-Interleukin-2, pubmed-meshheading:12797396-Killer Cells, Lymphokine-Activated, pubmed-meshheading:12797396-Leukemia, Erythroblastic, Acute, pubmed-meshheading:12797396-Leukocytes, Mononuclear, pubmed-meshheading:12797396-Lymphocytes, pubmed-meshheading:12797396-Melanoma, pubmed-meshheading:12797396-O(6)-Methylguanine-DNA Methyltransferase, pubmed-meshheading:12797396-Skin Neoplasms, pubmed-meshheading:12797396-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
DNA repair enzymes and cytotoxic effects of temozolomide: comparative studies between tumor cells and normal cells of the immune system.
pubmed:affiliation
Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't