| pubmed-article:10498620 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10498620 | lifeskim:mentions | umls-concept:C2323499 | lld:lifeskim |
| pubmed-article:10498620 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:10498620 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
| pubmed-article:10498620 | lifeskim:mentions | umls-concept:C1515655 | lld:lifeskim |
| pubmed-article:10498620 | lifeskim:mentions | umls-concept:C1517132 | lld:lifeskim |
| pubmed-article:10498620 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:10498620 | pubmed:dateCreated | 1999-11-4 | lld:pubmed |
| pubmed-article:10498620 | pubmed:abstractText | Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltransferase inhibitor (FTI) L-744,832 in an in vivo murine model of myeloid leukemia that is associated with inactivation of the Nf1 tumor suppressor gene. Nf1 encodes a GTPase activating protein for Ras, and Nf1-deficient (Nf1-/-) hematopoietic cells show hyperactive Ras signaling through the mitogen-activated protein (MAP) kinase pathway. L-744,832 inhibited H-Ras prenylation in cell lines and in primary hematopoietic cells and abrogated the in vitro growth of myeloid progenitor colonies in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). This FTI also partially blocked GM-CSF-induced MAP kinase activation, but did not reduce constitutively elevated levels of MAP kinase activity in primary Nf1-/- cells. Injection of a single dose of 40 or 80 mg/kg of L-744, 832 increased the amount of unprocessed H-Ras in bone marrow cells, but had no detectable effect on N-Ras. Adoptive transfer of Nf1-/- hematopoietic cells into irradiated mice induces a myeloproliferative disorder that did not respond to L-744,832 treatment. We speculate that the lack of efficacy in this model is due to the resistance of N-Ras and K-Ras processing to inhibition by this FTI. | lld:pubmed |
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| pubmed-article:10498620 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10498620 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:10498620 | pubmed:citationSubset | AIM | lld:pubmed |
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| pubmed-article:10498620 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10498620 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10498620 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:10498620 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10498620 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10498620 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:10498620 | pubmed:issn | 0006-4971 | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:TaylorB RBR | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:GibbsJ BJB | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:JacksTT | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:ShannonK MKM | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:KohlN ENE | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:MahgoubNN | lld:pubmed |
| pubmed-article:10498620 | pubmed:author | pubmed-author:GratiotMM | lld:pubmed |
| pubmed-article:10498620 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10498620 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:10498620 | pubmed:volume | 94 | lld:pubmed |
| pubmed-article:10498620 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10498620 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10498620 | pubmed:pagination | 2469-76 | lld:pubmed |
| pubmed-article:10498620 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:10498620 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10498620 | pubmed:articleTitle | In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells. | lld:pubmed |
| pubmed-article:10498620 | pubmed:affiliation | Department of Pediatrics, University of California, San Francisco, CA, USA. | lld:pubmed |
| pubmed-article:10498620 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10498620 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:10498620 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:18015 | entrezgene:pubmed | pubmed-article:10498620 | lld:entrezgene |
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