|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2005-8-22
|
|
pubmed:abstractText |
Patients with chronic lymphocytic leukemia (CLL) treated with adenovirus CD154 (Ad-CD154, CD40 ligand [CD40L]) gene therapy experienced rapid reductions in leukemia cell counts and lymph node size associated with the induced expression of Fas (CD95). However, CLL cells initially resist CD95-mediated apoptosis within the first 3 days after CD40 ligation in vitro. Thereafter, they become sensitive, which is associated with the CD40-induced expression of the proapoptotic protein B-cell leukemia 2 homology 3 (BH3) interacting domain death agonist (Bid). We hypothesized that the initial resistance to CD95-mediated apoptosis may be due to the high-level expression of X-linked inhibitor of apoptosis protein (XIAP) by CLL cells. Consistent with this, CLL cells from patients 1 day after treatment with autologous Ad-CD154-transduced CLL cells became sensitive to CD95-mediated apoptosis following treatment with a novel XIAP inhibitor, 1540-14. Similarly, 1540-14 specifically enhanced CD95-mediated apoptosis of CLL cells following CD40 ligation in vitro. Immunoblot analyses demonstrated that treatment with 1540-14 allowed CD40-stimulated CLL cells to experience high-level activation of caspases-8 and -3 and cleavage of poly(adenosine diphosphate [ADP]-ribose) polymerase following CD95 ligation. This study demonstrates that distal apoptosis regulators contribute to the initial resistance of CD40-activated CLL cells to CD95-mediated apoptosis and suggests that XIAP inhibitors might enhance the effectiveness of immune-based treatment strategies that target CD40, such as CD154 gene therapy.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-10433796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-10520003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-10578175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-10739652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-10810207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-10962579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11049967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11059757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11170835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11228391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11313271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11782443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11790791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11801595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11807010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-11891278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-12011074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-12181739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-12576463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-12700660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-14563117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-14749124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15048066,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15094781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15118763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15183896,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15282301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15324812,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15337764,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15339846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-15521917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-9384571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15914559-9545235
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylurea Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
0006-4971
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
106
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1742-8
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:15914559-Antigens, CD40,
pubmed-meshheading:15914559-Antigens, CD95,
pubmed-meshheading:15914559-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:15914559-Apoptosis,
pubmed-meshheading:15914559-Caspases,
pubmed-meshheading:15914559-Humans,
pubmed-meshheading:15914559-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:15914559-Molecular Conformation,
pubmed-meshheading:15914559-Molecular Weight,
pubmed-meshheading:15914559-Phenylurea Compounds,
pubmed-meshheading:15914559-Proteins,
pubmed-meshheading:15914559-Structure-Activity Relationship,
pubmed-meshheading:15914559-X-Linked Inhibitor of Apoptosis Protein
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis.
|
|
pubmed:affiliation |
Moores Cancer Center at the University of California, San Diego, School of Medicine, University of California, San Diego, CA 92093, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
