AEG35156, a XIAP antisense oligonucleotide, suppresses XIAP levels in targeted tissues isolated from pre-clinical models and from patients
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 4862 X-linked inhibitor of apoptosis (XIAP) is a potent anti-apoptotic protein whose over expression and dysfunction is associated with resistance to chemotherapy and radiotherapy. [AEG35156][1] is a synthetic 19-mer, 2nd generation, mixed backbone antisense oligonucleotide to human XIAP. Inhibition of XIAP expression by [AEG35156][1] enhances cancer cell apoptosis both in vitro and in vivo , either as a single agent or in combination with chemotherapeutic agents. In animal models, [AEG35156][1] reduced XIAP-mRNA and protein levels in representative tissues at therapeutically feasible doses. In a H460 human lung carcinoma xenograft study in mice, [AEG35156][1], effectively suppressed XIAP protein levels in tumors at doses that achieved dramatic reductions in the rate of tumor growth, particularly when combined with suboptimal doses of docetaxel. A murine-specific variant of [AEG35156][1] attenuated XIAP protein in circulating PBMCs and bone marrow when administered s.c. to mice at 80%. Flow cytometric analysis of the patient’s circulating blasts indicated a loss of XIAP protein, and elevated levels of activated caspase 3 and PARP cleavage during [AEG35156][1] infusion. XIAP antisense also caused a dose-dependent reduction in XIAP-mRNA in PBMCs in most patients, suggesting that these cells could serve as a surrogate to target effects in solid tumor tissue. Other trials with [AEG35156][1] are currently underway: a Phase 1 trial in combination with docetaxel in Canada (sponsored by National Cancer Institute of Canada), and an AML trial, in combination with idarubicin and ara-C, in the US and Canada. ( ) [1]: /lookup/external-ref?link_type=GENPEPT&access_num=AEG35156&atom=%2Fcanres%2F66%2F8_Supplement%2F1142.2.atom [2]: /lookup/external-ref?link_type=GENPEPT&access_num=AEG56156&atom=%2Fcanres%2F66%2F8_Supplement%2F1142.2.atom
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".