Abstract 3339: Elimination of cancer stem cells in pancreatic cancer cell lines by a combinatorial therapy
Bibliographic record
Abstract
Abstract Cancer stem cells (CSC) are tumor initiating cells and considered resistant to current conventional chemo and radio therapies. Consequently, novel strategies are needed to target these cells. Tumor cells expressing elevated levels of aldehyde dehydrogenase 1 family member A1 activity (ALDHbright cells) have been shown to have many properties attributed to CSC, including tumorigenicity in immunodeficient mice. We used FACS analysis to identify and sort ALDHbright cells from several human pancreatic cell lines using ALDEFLUOR (Stem Cell Technologies, Vancouver Canada). We show that ALDHbright but not ALDHnegative cells sorted from the human MiaPaCa-2 pancreatic adenocarcinoma cell are highly tumorigenic at low inoculum of 500 cells in immunodeficient NOD.SCID mice, a critical property of CSC. Previously, we identified the ALDH1A188–96 peptide as an HLA-A2-restricted, cytotoxic T cell (CTL)-defined tumor antigen. Using a flow cytometry-based assay, ALDHbright cells in the HLA-A2+ MiaPaCa-2 cell line were selectively eliminated in vitro by ALDH1A188–96 peptide-specific CTL. The Hedgehog (Hh) stem cell signaling pathway has been shown to play a critical role in invasion and metastasis in pancreatic cancer. Treatment of the MiaPaCa-2 cell line with the Hg inhibitor, cyclopamine, significantly eliminated ALDH+ MiaPaCA-2 cells compared to treatment with conventional chemotherapeutic agents. The efficacy of a combinatorial therapy consisting of adoptive transfer of ALDH1A1-specific CTL combined with systemic administration of cyclopamine in vitro and in vivo on ALDHbright cells and in vivo growth inhibition of MIA PaCa-2-derived xenografts is detailed. 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 3339.
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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 | 0.001 | 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".