| pubmed-article:12531810 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0038435 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0023434 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0178539 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0016693 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0312418 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0450442 | lld:lifeskim |
| pubmed-article:12531810 | lifeskim:mentions | umls-concept:C0036667 | lld:lifeskim |
| pubmed-article:12531810 | pubmed:issue | 10 | lld:pubmed |
| pubmed-article:12531810 | pubmed:dateCreated | 2003-5-6 | lld:pubmed |
| pubmed-article:12531810 | pubmed:abstractText | 2-Methoxyestradiol (2-ME), a new anticancer agent currently in clinical trials, has been demonstrated to inhibit superoxide dismutase (SOD) and to induce apoptosis in leukemia cells through a free radical-mediated mechanism. Because the accumulation of superoxide (O(2)-) by inhibition of SOD depends on the cellular generation of O(2)-, we hypothesized that the endogenous production of superoxide may be a critical factor that affects the antileukemia activity of 2-ME. In the present study, we investigated the relationship between cellular O(2)- contents and the cytotoxic activity of 2-ME in primary leukemia cells from 50 patients with chronic lymphocytic leukemia (CLL). Quantitation of O(2)- revealed that the basal cellular O(2)- contents are heterogeneous among patients with CLL. The O(2)- levels were significantly higher in CLL cells from patients with prior chemotherapy. CLL cells with higher basal O(2)- contents were more sensitive to 2-ME in vitro than those with lower O(2)- contents. There was a significant correlation between the 2-ME-induced O(2)- increase and the loss of cell viability. Importantly, addition of arsenic trioxide, a compound capable of causing reactive oxygen species (ROS) generation, significantly enhanced the activity of 2-ME, even in the CLL cells that were resistant to 2-ME alone. These results suggest that the cellular generation of O(2)- plays an important role in the cytotoxic action of 2-ME and that it is possible to use exogenous ROS-producing agents such as arsenic trioxide in combination with 2-ME to enhance the antileukemia activity and to overcome drug resistance. Such a combination strategy may have potential clinical applications. | lld:pubmed |
| pubmed-article:12531810 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12531810 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12531810 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12531810 | pubmed:month | May | lld:pubmed |
| pubmed-article:12531810 | pubmed:issn | 0006-4971 | lld:pubmed |
| pubmed-article:12531810 | pubmed:author | pubmed-author:ZhouYanY | lld:pubmed |
| pubmed-article:12531810 | pubmed:author | pubmed-author:PlunkettWilli... | lld:pubmed |
| pubmed-article:12531810 | pubmed:author | pubmed-author:HuangPengP | lld:pubmed |
| pubmed-article:12531810 | pubmed:author | pubmed-author:KeatingMichae... | lld:pubmed |
| pubmed-article:12531810 | pubmed:author | pubmed-author:HilemanElizab... | lld:pubmed |
| pubmed-article:12531810 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12531810 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:12531810 | pubmed:volume | 101 | lld:pubmed |
| pubmed-article:12531810 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12531810 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12531810 | pubmed:pagination | 4098-104 | lld:pubmed |
| pubmed-article:12531810 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:meshHeading | pubmed-meshheading:12531810... | lld:pubmed |
| pubmed-article:12531810 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12531810 | pubmed:articleTitle | Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents. | lld:pubmed |
| pubmed-article:12531810 | pubmed:affiliation | Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. | lld:pubmed |
| pubmed-article:12531810 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12531810 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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