Matrix Metalloproteinases-2 and 9 Do Not Play a Role in the Growth of Preneoplastic Liver Lesions in F344 Rats
Bibliographic record
Abstract
Matrix metalloproteinases- (MMPs) 2 and 9 (gelatinases A and B) have been implicated in tumor invasion and metastasis, and recent studies have shown increased levels of these enzymes during recovery from partial hepatectomy (PH) in rats. F344 rats are highly susceptible to the growth of glutathione S-transferase 7-7- (GST 7-7) positive preneoplastic liver lesions promoted using the modified resistant hepatocyte (RH) protocol. Since the RH protocol consists of 2-acetylaminofluorene (2-AAF) followed by a PH, we reasoned that MMP-2 and -9 might be critical for the growth of lesions. Using gelatin zymography, we examined the expression of these enzymes in the livers of F344 rats treated with the RH protocol and sacrificed on Days 2, 4, 7, 14, and 21 after 2-AAF/PH. We found increases in both pro- and active MMP-2 and -9 over baseline levels, with the highest levels occurring on Day 7 post-PH. Also, a 54-kDa band, likely to be proMMP-1, was elevated in a pattern similar to MMP-2 and -9. In contrast to F344 rats, identically treated Copenhagen rats that are highly resistant to promotion of liver lesion growth using the RH protocol had significantly lower levels of proMMP-1 and -2. To test the importance of these MMPs to the growth of liver lesions, F344 rats that had been initiated with diethylnitrosamine were treated using the RH protocol. They then received either the MMP inhibitor batimastat (30 mg/kg, intraperitoneally) or vehicle alone daily from Day 3 to 20 post-PH and were sacrificed on Day 21. There were no differences in the percentage of liver volume occupied by GST 7-7-positive lesions (19.1 +/- 4.84 vs 19.4 +/- 3.31, treated versus vehicle, mean +/- SEM) or liver weight as a percentage of body weight (4.11% +/- 0.15 vs 4.07% +/- 0.18, treated versus vehicle, mean +/- SEM) between the treated and control groups. Treatment of rats with batimastat clearly did not affect lesion growth or liver regeneration following the RH protocol. These results suggest that increases in gelatinase expression during the RH protocol are a result of the promotional stimulus rather than a mechanism by which 2-AAF/PH causes lesion growth.
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 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".