Abstract 3661: Vascular changes and potentiating secondary drug delivery in colorectal cancer with Irinophore C
Bibliographic record
Abstract
Abstract Introduction: Colorectal cancer is the third most common cancer in the world. The predominant chemotherapeutic treatment in CRC is a combination of 5-fluorouracil (5-FU) and irinotecan (CPT-11). However, the combination is limited by toxicity and resistance. We now report on the effects of 5-FU in combination with a liposomal formulation of CPT-11, Irinophore C, that is more efficacious and less toxic than free CPT-11. Materials and Methods: 5-FU was used singly and in combination with Irinophore C in a subcutaneous model of colorectal cancer, HT-29, to assess therapeutic efficacy and toxic effects. 5-FU and Irinophore C (40mg/kg) were injected intravenously on a Q7Dx3 schedule, and tumor growth delay was measured. In a subsequent study, a single bolus injection of 14C-spiked 5-FU was delivered at different timepoints during Irinophore C (tritium-labeled) or saline treatment (Q7Dx3), and the accumulation of 5-FU in tumor tissue measured with scintigraphy. Tumors were also harvested and snap-frozen at early (days 1 - 7) and late (days 14 and 21) time points following Irinophore C treatment. Cryosections were subsequently examined for perfusion using the fluorescent dye Hoechst 33342, stained for apoptosis (TUNEL), CD31, CD105, Collagen IV and with H&E to examine changes in vascular function and tissue morphology. Results: Irinophore C significantly reduced tumour growth (p<0.001) with little or no toxicity compared to saline controls, 5-FU alone and free CPT-11 plus 5-FU. In some cases, tumour growth was completely abolished. When used in combination with 5-FU, there was a slight increase in growth delay. Treatment of the tumours with Irinophore C increased the accumulation of the active lactone form of the drug in the tumour, and also significantly increased the tissue accumulation of a single bolus injection of 5-FU after two (∼50% increase, p<0.001) and three weeks (∼66% increase, p<0.001). Following treatment with Irinophore C, the density of tumor tissue was decreased, and the vascular coverage was increased, leading to increased total perfusion. In addition, apoptotic activity was increased following 1 to 2 weeks of treatment with Irinophore C, compared to controls. Conclusions: Irinophore C is more efficacious, and less toxic, than free CPT-11. This novel formulation of CPT-11 appears to have a bimodal mechanism of action wherein both endothelial and cancer cells are targeted, and which may improve the delivery of a second drug. We further believe that the dose of Irinophore C used in the combination studies is with 5-FU is overly efficacious and masks the effects of 5-FU. Clinically, Irinophore C with its low toxicity and high efficacy could have advantages over the use of free CPT-11. 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 3661.
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".