Abstract | PURPOSE:
Cancer cells can use X-linked inhibitor of apoptosis (XIAP) to evade apoptotic cues, including chemotherapy. The antitumor potential of AEG35156, a novel second-generation antisense oligonucleotide directed toward XIAP, was assessed in human cancer models when given as a single agent and in combination with clinically relevant chemotherapeutics. EXPERIMENTAL DESIGN:
AEG35156 was characterized for its ability to cause dose-dependent reductions of XIAP mRNA and protein in vitro and in vivo, to sensitize cancer cell lines to death stimuli, and to exhibit antitumor activity in multiple human cancer xenograft models as a single agent or in combination with chemotherapy. RESULTS: CONCLUSIONS:
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Authors | Eric C LaCasse, Gabriele G Cherton-Horvat, Kimberley E Hewitt, Lori J Jerome, Stephen J Morris, Ekambar R Kandimalla, Dong Yu, Hui Wang, Wei Wang, Ruiwen Zhang, Sudhir Agrawal, John W Gillard, Jon P Durkin |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 12
Issue 17
Pg. 5231-41
(Sep 01 2006)
ISSN: 1078-0432 [Print] United States |
PMID | 16951243
(Publication Type: Journal Article)
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Chemical References |
- AEG 35156
- Antineoplastic Agents
- Oligodeoxyribonucleotides, Antisense
- Oligonucleotides
- RNA, Messenger
- TNF-Related Apoptosis-Inducing Ligand
- Taxoids
- X-Linked Inhibitor of Apoptosis Protein
- Docetaxel
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Disease Models, Animal
- Docetaxel
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Drug Synergism
- Gene Expression Profiling
- Humans
- Mice
- Mice, Nude
- Neoplasms
(drug therapy)
- Oligodeoxyribonucleotides, Antisense
(pharmacology)
- Oligonucleotides
(pharmacology)
- RNA, Messenger
(drug effects, genetics)
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
- Sensitivity and Specificity
- Structure-Activity Relationship
- TNF-Related Apoptosis-Inducing Ligand
(pharmacology)
- Taxoids
(therapeutic use)
- Transplantation, Heterologous
- X-Linked Inhibitor of Apoptosis Protein
(antagonists & inhibitors, genetics)
- Xenograft Model Antitumor Assays
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