Liposome formulations of combretastatin a4 and 4-arylcoumarin analog prodrugs: antitumor effect in the mouse model of breast cancer
Bibliographic record
Abstract
The antimitotic agent combretastatin A4 (CA-4) has been suggested as an antivascular agent for anticancer therapy relatively recently. To reduce systemic toxicity by means of administration in liposome formulations, in this study new lipophilic prodrugs, oleic derivatives of CA-4 and its 4-arylcoumarin analog (CA4-Ole and ArC-Ole, respectively), have been synthesized: Liposomes of 100 nm mean diameter prepared on the basis of egg phosphatidylcholine and phosphatidylinositol from bakers yeast have been shown to include completely up to 10 mol. % of CA4-Ole, or 7 mol. % of ArC-Ole. Also, prodrug bearing liposomes decorated with tetrasaccharide selectin ligand Sialyl Lewis X (SiaLe(x)) have been constructed to achieve targeting to endothelium under neovascularization. The antitumor activity in vivo was studied in the model of slowly growing mouse breast cancer. Under the used dose (22 mg/kg) as well as the regimen of treatment (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal any anticancer effect, and oppositely even stimulated tumor growth. Liposome formulations of CA4-Ole did not show such stimulation. However, to achieve pronounced antitumor effect, number of injections of liposomes should be apparently elevated. New antimitotic agent ArC revealed cytotoxic activity of only one tenth value obtained for CA-4 in vitro in the culture of human breast carcinoma cells. Nevertheless, in vivo in the mouse model of breast cancer this compound showed antitumor effect under double CA-4 equivalent dose. The results demonstrate availability of SiaLe(x)-liposomes loaded with ArC-Ole: this preparation began to inhibit tumor growth already after the second injection. It is necessary further to choose doses and regimens of administration both for ArC and liposome formulations bearing ArC-Ole.
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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) | 0.000 | 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".