Linked Life Data

17184908

Source:http://linkedlifedata.com/resource/pubmed/id/17184908

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-4-23
pubmed:abstractText
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumorigenic and transformed cell lines but not in many normal cells. Hence, TRAIL-agonist compounds have the potential of being excellent cancer therapeutic agents with minimal cytotoxicity. Here, we examine the efficacy of the TRAIL-receptor 2 agonist, lexatumumab (Human Genome Sciences, Inc., Rockville, MD), and identify molecular pathways that differentiate between lexatumumab-sensitive and lexatumumab-resistance renal cancer cells. In an orthotopic metastatic mouse model, we first demonstrate that lexatumumab was effective in reducing the tumor burden of primary and metastatic lexatumumab-sensitive xenografts. We demonstrate that lexatumumab-sensitive cells were capable of triggering both the extrinsic and the intrinsic apoptotic pathways as demonstrated by caspase 8 and caspase 9 activations, respectively, after treatment with lexatumumab. In addition, expression of c-FLIP(L) protein, an important regulator of TRAIL-induced apoptosis, decreased, while expression of the TRAIL-receptor 2, DR5, increased. This study serves as a pre-clinical model for using TRAIL-like therapies for patients with advanced RCC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
251
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
146-57
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17184908-Animals, pubmed-meshheading:17184908-Antibodies, Monoclonal, pubmed-meshheading:17184908-Apoptosis, pubmed-meshheading:17184908-Blotting, Western, pubmed-meshheading:17184908-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:17184908-Carcinoma, Renal Cell, pubmed-meshheading:17184908-Cell Line, Tumor, pubmed-meshheading:17184908-Cell Survival, pubmed-meshheading:17184908-Dose-Response Relationship, Drug, pubmed-meshheading:17184908-Humans, pubmed-meshheading:17184908-Immunohistochemistry, pubmed-meshheading:17184908-Kidney Neoplasms, pubmed-meshheading:17184908-Mice, pubmed-meshheading:17184908-Mice, Nude, pubmed-meshheading:17184908-Receptors, TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:17184908-Tumor Burden, pubmed-meshheading:17184908-Xenograft Model Antitumor Assays
pubmed:year
2007
pubmed:articleTitle
Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic model.
pubmed:affiliation
Division of Urologic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural