Abstract 4420: Serum regulates reovirus-mediated cytopathy in K-Ras activated colorectal cancer and intestinal epithelial cell lines
Bibliographic record
Abstract
Abstract Background: The oncolytic potency of replication competent REOvirus has been demonstrated in various cancers. The activity is most pronounced in Kras mutant cancer cells, which account for 30-40 % of all cancers. Herein we simultaneously utilized isogenic human derived colorectal cancer cell lines that differ only by the presence of mutant Kras and normal rat intestinal epithelial cells with inducible Kras to evaluate whether the presence of oncogenic Kras alters the sensitivity of colon cancer cells to reovirus. Methods: Reovirus was obtained from Oncolytics Biotech Inc. Rat IEC's harboring IPTG inducible mutant Ras oncogene (IEC-iKras) were treated with reovirus ± IPTG. The infectivity was maintained at a multiplicity of infection (MOI) of 2. MTT assay was performed at 72 hours to determine cell vability (CV). Similar experiments were also performed with HCT116 (Kras mut) and its isogenic derivative Hke3 [(Kras wild type (WT)]. Cells were cultured and treated in both serum rich (SR) and serum free (SF) media to determine the effect of growth factors on sensitivity to reovirus. Alterations in gene expression were determined by real time PCR and protein expression by western blot. Results: The activity of reovirus was observed in all cell lines studied. Reduction in CV was greater in Kras mutant HCT116 compared to WT Hke3 cells. Consistently, induction of Kras in IEC cells increased the potency of reovirus. Furthermore, this effect was more prominent in cells cultured in SF suggesting that growth factors in the serum may attenuate the effect of mutant Kras on reovirus sensitivity. Expression of the cell cycle regulator, p21 was preferentially increased upon reovirus infection in Kras mutant compared to WT cells, and in cells cultured in SF compared to SR conditions. Conclusion: Oncogenic Kras mutations increase the sensitivity of colon cancer cells to Reovirus. Clinical trials are underway testing reovirus in patients with Kras mutant metastatic colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4420. doi:1538-7445.AM2012-4420
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".