PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis
Bibliographic record
Abstract
Preclinical and clinical studies have demonstrated the anticancer activity of PD-0332991, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, in the treatment of various types of cancer in a retinoblastoma protein (RB)-dependent manner. However, it remains unclear whether CDK4, CDK6 or both are required for RB phosphorylation in colorectal carcinoma and thus PD-0332991 can be used to target this CDK-RB axis for the cancer therapy. The aim of this study was to determine whether CDK4, CDK6 and phosphorylated RB proteins were overexpressed in colorectal carcinoma tissues as compared to matched normal colorectal tissues. The results showed that knockdown of CDK6 but not CDK4 reduced RB phosphorylation and inhibited carcinoma cell growth. Thus, CDK6 plays a critical role in RB phosphorylation and cancer growth. PD-0332991 treatment blocked RB phosphorylation and inhibited cell growth through the induction of G1 arrest of colorectal carcinoma cells. The results demonstrated that, by targeting of CDK6-RB axis, PD-0332991 may prove to be a novel therapeutic agent in treating colorectal carcinoma.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".