Phosphodiesterase inhibition as an approach to increase chemosensitivity of prostate cancer
Bibliographic record
Abstract
691 Purpose: Low tumour oxygenation (hypoxia) correlates with resistance to chemotherapeutic agents. We have recently provided evidence that hypoxia-induced resistance to anti-cancer drugs can be decreased by stimulating nitric oxide (NO) signalling through a cGMP-mediated pathway. An alternative approach to increase the activity of this signalling pathway is to prevent the breakdown of cGMP by phosphodiesterases (PDEs). The aim of this study was to determine whether PDE inhibitors are capable of attenuating hypoxia-induced chemoresistance in prostate carcinoma cells. Materials and Methods: Western blots, immunohistochemistry and functional enzymatic assays were used to determine the expression of PDEs in human cell lines and human prostate cancer samples. Drug sensitivity assays of cell lines exposed to hypoxic or standard conditions were performed in the presence of various concentrations of the PDE-5-specific inhibitor zaprinast. Results: These studies revealed the presence of two of the multiple cGMP-specific PDEs (PDE5 and PDE11A) in both DU145 and PC-3 cell lines and in prostate cancer tissue. Clonogenic assays revealed that incubation of DU145 in 0.5% O2 for 24 hours resulted in a corresponding 4-fold increase (P
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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".