Abstract 382: Platelets are implicated in the rapid host responses induced by cytotoxic chemotherapy which limit its anti-tumor efficacy
Bibliographic record
Abstract
Abstract Previous studies from our lab have shown that the overall anti-tumor impact of certain cytotoxic drugs such as paclitaxel (PTX) given at maximum tolerated doses (MTDs) or OXi-4503, a microtubule inhibiting vascular disrupting agent (VDA), can be reduced by a rapid systemic counter-acting host response (Y Shaked et al., Science 2006 and Cancer Cell 2008). The aforementioned host response includes rapid induction of elevated plasma levels of multiple cytokines or chemokines such as G-CSF and SDF-1, which can promote mobilization and tumor-homing/colonization of proangiogenic and tumor-growth promoting bone marrow-derived cells (BMDCs), including circulating endothelial progenitor cells. This reactive host response promotes recovery/repopulation of the drug treated tumor. Here we asked what might be the source(s) of the elevated levels of plasma chemokines and cytokines induced by MTD PTX. We found platelets - known major sources of SDF-1 and VEGF - become activated and release the contents of their alpha granules into the circulation (plasma), such that decreases in platelet associated SDF-1 (and VEGF) are observed accompanied by increases in their plasma levels. SDF-1 is known to mobilize a variety of BMDCs including CEPs. Because platelets are not known to be a source of G-CSF - which is also elevated in the plasma by MTD PTX - other cellular and/or non-cellular sources are likely affected as well by the drug treatment. We also found that pharmacologic-mediated reductions in platelet numbers or activation results in reduced expression of the counter-acting host cytokine/chemokine response induced by MTD PTX treatment, thus providing further support for a contribution of platelets. Finally we have found low-dose metronomic chemotherapy does not induce the counter acting host response which is likely due in part to a lack of effect on platelets. In summary, our results implicate a new way in which platelets can impact tumor biology and response to therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 382.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.017 | 0.004 |
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".