Bibliographic record
Abstract
Obesity is associated with an elevated risk of colorectal cancer (CRC) and is the most common underlying cause of insulin resistance. Hyperinsulinemia promotes CRC but it is not clear whether other factors associated with obesity and insulin resistance are causally involved. The hypothesis of this work was that elevated adiposity and its associated hyperlipidemia, IGF-I and leptin are each promoters of colon carcinogenesis, independent of changes in insulin. I first compared susceptibility to colon carcinogenesis in Muscle-specific Insulin Receptor Knockout (MIRKO) mice that have increased fat mass and elevated serum triglycerides (TG) and free fatty acids (FFA) but similar body weights, circulating glucose and insulin sensitivity to their wildtype littermate controls. My results suggested that TG and FFA are not promoters of colon tumor development and that increased accumulation of insulin-sensitive adipose tissue may have inhibited the growth of preneoplastic aberrant crypt foci (ACF) into tumors in MIRKO mice. In the second study, I assessed susceptibility to colon carcinogenesis in liver-specific IGF-I deficient (LID) mice that exhibit a 70% reduction in circulating IGF-I compared to littermate controls. IGF-I deficiency attenuated the promoting effect of insulin on colon carcinogenesis and IGF-I acted as an independent promoter of the growth of established tumors. In the third study, I compared susceptibility to colon carcinogenesis in obese leptin-deficient ob/ob mice and db/db mice that are also obese but have highly elevated circulating leptin. My data showed that leptin does not play a role in ACF development. In the last study I compared regulation of cytochrome P450 2E1 (CYP2E1) by the colon-specific carcinogen azoxymethane (AOM) and by leptin in ob/ob and db/db mice based on my finding that repeated weekly treatment with AOM to induce colon tumors was hepatoxic to db/db mice. I observed that leptin modifies AOM-induced changes in hepatic CYP2E1 activity. In conclusion, I have found that elevated circulating TG, FFA and leptin do not promote colon carcinogenesis independent of changes in insulin. Elevated adiposity may protect against colon carcinogenesis depending on the metabolic milieu of the adipocyte. My work also suggests that IGF-I is a good molecular target for colon cancer chemoprevention.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".