Approaches to the discovery of biomarkers of prostate carcinogenesis in TRAMP mice and of chemopreventive efficacy of tea polyphenols
Bibliographic record
Abstract
To improve prostate cancer management in humans who have, or are at risk of\ndeveloping, the disease, biomarkers are required to aid early diagnosis and\nmonitoring of response to chemotherapeutic or chemopreventive intervention.\nIn this project metabonomic and peptidomic approaches were used to study\nbiological changes associated with prostate carcinogenesis in a transgenic mouse\nmodel (TRAMP, TRansgenic Adenocarcinoma of the Mouse Prostate). Observed\nchanges were compared with pathological alterations. Metabolome and peptidome\nanalyses were conducted in TRAMP mice exposed to chemopreventive intervention\nwith green tea polyphenols (GTP). Effects of consumption of GTP or black tea\ntheaflavins on the plasma and urine metabonome/peptidome in patients with benign\nprostatic hyperplasia (BPH) were also investigated. Oxidative stress status reflected\nby urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) was assessed in mice\nand humans on tea polyphenols.\nMetabonomic profiling revealed that at early stages of carcinogenesis in mice,\nalterations of tumour levels of choline metabolites resembled the human disease. In\ncontrast, in advanced stages of TRAMP prostate carcinogenesis, phospholipid\nmetabolism is affected differently by malignancy than in its human counterpart.\nDisturbed prostate-specific citrate metabolism seems common to both human and\nTRAMP prostate tumours when compared to normal tissue. These results suggest\nthat the TRAMP mouse may be a better model with respect to humans of early stage\ncarcinogenesis with minor proliferative lesions than of more advanced stages of\nmalignancy.\nUrinary 8-oxodG levels were not affected by presence of prostate cancer or\nintervention with tea. Metabolic profiling gave evidence for an effect of GTP on\nenergy metabolism in both mice and humans. Although TRAMP and GTP-groupspecific\nmetabonomic and peptidomic changes were found in plasma and urine, none\nof these metabolites or peptides could be unambiguously identified as biomarkers of\ncarcinogenesis or GTP exposure. Among possible confounding factors which should\nbe taken into consideration in future metabonomic/peptidomic studies is the host’s\ngut microflora.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".