Role of Gas6 in Cancer-Induced Venous Thrombosis
Bibliographic record
Abstract
Abstract Abstract 108 Venous thrombosis is the most common morbid complication related to cancer and its treatments. The onset of cancer has been shown to predispose patients to hemostatic disorders mainly because of the pro-thrombotic milieu generated by the cancer. Growth arrest specific 6 (gas6) is a vitamin K dependent secreted protein that is expressed by different cell types. Gas6 and its receptor Axl are overexpressed in different cancers. Gas6 null mice have been shown to be protected against life-threatening thrombosis. Because of the association of gas6 with cancer and thrombosis, the objective of the present study is to elucidate the role of gas6 in cancer-induced venous thrombosis. Thus, we hypothesize that the absence of gas6 in a mouse model of cancer would reduce venous thrombosis. Wild type (WT) and gas6 null (−/−) mice received an intravenous injection of M27 murine lung cancer cells. After 2 weeks, WT and gas6−/− mice developed end stage cancer. Venous thrombosis was induced using 10% ferric chloride. Thrombus surface area was evaluated using ultrasonography, 30 minutes after ferric chloride application. We found that thrombi induced in mice with cancer were smaller than those induced in WT mice, by both ultrasound (p<0.05) and histologically (p<0.05). To elucidate the role of gas6 in cancer-induced thrombosis, we co-cultured murine endothelial cells, prepared from lungs of both WT and gas6−/− mice, with M27 cells. RNA was extracted from endothelial cells and we used a whole genome microarray analysis to identify differential gene expression induced by cancer in the presence or absence of gas6. Microarray analysis revealed that 28 genes were differentially expressed in WT or gas6−/− cells in the presence of cancer. Of interest, we found that thrombospondin 2 was downregulated by cancer cells in WT endothelial cells and even further decreased in gas6−/− cells. We confirmed these results using real-time qPCR and western blot analysis (p<0.05). These results suggest the possibility that gas6, through the downregulation of thrombospondin 2, has a pathophysiologic role in cancer-induced thrombosis. Disclosures: No relevant conflicts of interest to declare.
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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".