Expression of Endothelins and Their Receptors in Nonmelanoma Skin Cancers
Bibliographic record
Abstract
BACKGROUND: Endothelins are paracrine peptides with growth-promoting and vasoactive functions for a variety of cell types. Elevated activation of the endothelin signaling pathway induces cell proliferation and/or survival and is implicated in a variety of malignancies. Increased endothelin 1 was described in solar lentigines in previous reports, raising the possibility that the endothelin pathway may be of significance in keratinocyte proliferation-related disorders. However, detailed investigation on endothelins in skin malignancies is lacking. OBJECTIVES: This study aims to survey the expression of endothelins and their receptors in keratinocyte-derived benign and malignant tumors of the skin and to test the effects of endothelin inhibitors on the growth and survival of cultured keratinocytes. METHODS: Quantitative polymerase chain reaction was used to measure the level of gene transcription of three endothelins (ET-1, -2, and -3) and two endothelin receptors (ETRA and ETRB). The genes with significant messenger ribonucleic acid (mRNA) expression abnormalities were confirmed with immunohistochemical analysis to examine expression differences at the protein levels. To analyze the effect of endothelin inhibitors on the keratinocyte growth and survival, keratinocytes were cultured in the presence of various concentrations of endothelin inhibitors and subjected to tetrazolium bromide assay to quantify the cell numbers over time. RESULTS: ET-1 mRNA was found to be significantly up-regulated in seborrheic keratosis and basal cell carcinoma. However, no significant expression increase was found in actinic keratosis, Bowen's disease, or squamous cell carcinoma. Immunohistochemical analysis of ET-1 peptide confirmed increased expression. In cultured keratinocytes, peptide inhibitors of the endothelin pathway resulted in a marked reduction in cell survival. CONCLUSION: The endothelin signaling pathway, especially ET-1, is activated in basal keratinocyte neoplasms of the skin, such as basal cell carcinoma and seborrheic keratosis. Blockade of this pathway can reduce cell survival in vitro. Therefore, endothelin inhibitors potentially offer a novel method for the treatment of some keratinocyte-derived skin tumors.
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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 | 0.001 | 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) | 0.001 | 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".