Isolation and Characterization of Colon Cancer-initiating Cells
Bibliographic record
Abstract
Colorectal cancer is the second leading cause of death from cancer (men and women combined) in the U.S. and Canada. The mainstay of treatment remains surgical resection and although new agents are constantly emerging to treat colorectal cancer, to date none of the agents have been successful at curing patients with advanced disease. In recent years there has been an increasing interest in the notion that cancers are organized as a hierarchy with the cancer-initiating cell (C-IC or cancer stem cell) existing at the apex. The C-ICs only represent a subset of the total tumour cells; however, research indicates that they are responsible for both the initiation and maintenance of tumour growth. In the studies presented here, we determined that human colon cancers are organized in a hierarchical manner. Furthermore, we prospectively isolated a subset of colon cancer-initiating cells (CC-ICs) based on the expression of the cell surface marker, CD133. The identification of CC-ICs has led to a number of questions concerning the molecular mechanisms driving these cells. Functionally all C-ICs are characterized by their ability to: i) generate a xenograft that histologically resembles the parent tumour from which it was derived, (ii) be serially transplanted in a xenograft assay thereby demonstrating the ability to self-renew and, (iii) generate daughter cells that possess some proliferative capacity but are unable to maintain the cancer because they lack intrinsic regenerative potential. It is becoming evident that cancer cells evolve as a result of their ability to hijack normal self-renewal pathways, a process that can drive malignant transformation. Studying self-renewal in the context of cancer and C-IC maintenance will lead to a better understanding of the mechanisms driving tumour growth. In this work we demonstrate that the inhibitors of differentiation genes (Id1 and Id3) play a central role in driving self-renewal in the CC-IC subset. Furthermore, we demonstrate that this effect is partially mediated through the cdk-inhibitor, p21cip1/waf1.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".