Abstract B12: The effects of Irinophore C™ on the microenvironment and vasculature of a primary orthotopic model of colorectal cancer.
Bibliographic record
Abstract
Abstract Introduction: Colorectal cancer is a common cancer that accounts for ∼10% of cancer cell deaths in North America. There are numerous in vivo xenograft models for colorectal cancer available, but in general, these are derived from immortalized cell lines and fail to capture the complexities and heterogeneity of tumors seen in the clinic. Our group has developed a series of orthotopic, primary tumors from samples of human colorectal cancer tissue obtained during surgical resection that maintain the characteristics of the original sample. The effects of Irinophore C™, (a liposomal formulation of irinotecan that is more efficacious and less toxic than the parent drug) on the microenvironment and vascular function of these primary colorectal tumors were examined in the present study. Materials and Methods: Primary tumor tissues, obtained from colorectal cancer patients, were validated by a reference pathologist and implanted subcutaneously in SCID mice. Small pieces of subcutaneous tumors that grew successfully were then passaged orthotopically on the ascending colon of new mice. When these tumors reached ∼200mm3, groups of mice were treated with vehicle control (0.9% saline), irinotecan (50mg/kg), or Irinophore C™ (25mg/kg) once a week for 6 weeks. Separate groups of tumors were harvested on days 3 and 42 after treatment started. Immunofluorescence staining was performed on tumor cryosections followed by computerized image analysis to determine levels of cell proliferation, apoptosis, hypoxia, and vessel density. Results: 4 of 14 samples were successfully propagated orthotopically and were characterized by a reference pathologist. The tumors maintain their original morphology, and one is a highly mucinous adenocarcinoma whereas the others are typical colorectal adenocarcinomas. Treatment with irinotecan and Irinophore C™ reduced tumor volumes by 54% and 92%, respectively, compared to the vehicle control. No toxic effects were seen with Irinophore C™. Immunostaining data showed that the distance between blood vessels remained the same for Irinotecan when compared to control, but increased with Irinophore C™ treatment (+30%; P<0.01). However, perfusion was not significantly different between the three treatment groups. Furthermore, compared to the vehicle treatment group, tumors treated with irinotecan are 42% (P<0.05) more necrotic and tumors treated with Irinophore C™ are 97% less hypoxic. Conclusion: An orthotopic model of colorectal cancer was successfully developed using patient tumor materials that retained the morphology of the primary tumor. Irinophore C™ was more effective in controlling tumor growth than irinotecan despite being delivered at a lower dose. In addition, treatment with Irinophore C™ appeared to improve overall vascular function in the tumor. Based on these data, it is clear that Irinophore C™ has different mechanisms of action and is more efficacious than irinotecan against primary models of colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B12.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".