Impact of circulating endothelial progenitor cells on the growth of viable tumor rim after treatment with a vascular disrupting agent.
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 5710 Unlike most antiangiogenic drugs, vascular disrupting agents (VDAs) can cause an acute shutdown in tumor blood flow, leading to a subsequent rapid cytotoxic-like process of extensive tumor necrosis. However, the impact of this therapeutic effect is compromised by a remaining viable tumor rim, from which the tumors can rapidly re-grow, a process accompanied by robust angiogenesis. This suggests that the use of a VDA with an antiangiogenic agent e.g., anti-VEGFR-2 antibodies, could be a very effective combination vascular targeting treatment, for which there is some evidence. The basis for rapid and robust angiogenesis at the viable tumor rim after VDA treatment is unclear. We hypothesized that in addition to exploiting the vasculature of the surrounding normal tissue, angiogenesis at the viable rim after VDA treatment must be facilitated by a compensatory host process. We present evidence that the immediate influence of bone marrow derived endothelial progenitor cells (CEPs) homing to the rim, may indeed represent such a contributory mechanism. Thus we found the following: i) administration of a VDA (CA4P or Oxi-4503) to normal (non tumor bearing) mice leads to a marked (3 fold) increase in CEP levels in peripheral blood within 4 hours - in contrast to antiangiogenic agents such as anti-VEGFR-2 antibody (e.g. DC101), which suppress CEPs levels; ii) the CEPs ‘home’ to the viable tumor rim after VDA treatment in two distinct tumor models (human melanoma xenograft and Lewis lung mouse carcinoma); iii) administration of DC101 24 hours prior to the VDA prevents the spike in CEPs which leads to virtually complete obliteration of the viable tumor rim; iv) administration of Oxi-4503 to Id mutant tumor-bearing mice, which cannot mobilize CEPs, leads to a powerful anti-tumor effect, compared to wild type control mice. Overall, our results suggest a compelling role for CEPs in the response to VDAs, and hence, a strategy to maximize the therapeutic potential of both VDAs and antiangiogenic drugs.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".