Metronomic ABI-007 therapy: antiangiogenic and antitumor activity of a nanoparticle albumin-bound paclitaxel
Bibliographic record
Abstract
2988 Background: Metronomic chemotherapy, the low-dose and frequent administration of cytotoxic agents without prolonged drug-free breaks, is believed to target activated endothelial cells in the tumor vasculature. A number of preclinical studies have demonstrated the superior antitumor efficacy and the reduced toxicity of some metronomic regimens compared to their maximum tolerated dose (MTD) counterparts. It remains unclear whether all chemotherapeutic drugs exert similar effects or whether some are better suited for such regimens than others. Paclitaxel has been shown to inhibit angiogenesis when used at very low doses (Grant et al., Int. J. Cancer, 2003). However, it was also reported that clinically relevant concentrations of the formulation vehicle cremophor EL in Taxol nullify the antiangiogenic activity of paclitaxel, suggesting that this agent or other anticancer drugs formulated in cremophor EL may need to be used at much higher doses than anticipated to achieve effective metronomic chemotherapy (Ng et al., Cancer Res., 2004). As such, the advantage of the lack of undesirable side effects associated with low-dose paclitaxel regimens vs. conventional MTD chemotherapy may be compromised. ABI-007, a cremophor EL-free nanoparticle paclitaxel, could potentially alleviate the problem. Methods: The antiangiogenic activity of ABI-007 was assessed by the rat aortic ring, human umbilical vein endothelial cell (HUVEC) proliferation and tube formation assays. Optimal dose of ABI-007 for metronomic therapy was determined by measuring the levels of circulating endothelial progenitors (CEPs) in peripheral blood of Bal/c non-tumor bearing mice (n=5/ group; dosing: 1-30 mg/kg, i.p, qdx7) with flow cytometry (Shaked et al., Cancer Cell, in press). Subsequently, the antitumor effects of metronomic (qd; i.p.) and MTD (qdx5, 1 cycle; i.v.) ABI-007 and Taxol were evaluated and compared in SCID mice bearing human MDA-MD-231 breast and PC3 prostate cancer xenografts. Results: ABI-007 at 5 nM significantly (P
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".