Fibroblast Growth Factor Receptors as Molecular Targets in Thyroid Carcinoma
Bibliographic record
Abstract
Several molecular abnormalities of potential therapeutic target value have been described in thyroid neoplastic transition. We report the expression of the fibroblast growth factor receptor family (FGFR-1-4) in normal thyroid tissues, human thyroid cancers of various types and behaviors, and cell lines representative of the spectrum of differentiation of tumors derived from follicular epithelial cells. FGFR-2 was the only receptor consistently detected in normal human thyroid tissue, and its expression diminished in all thyroid cancers and carcinoma cell lines, suggesting that it may have a protective role. FGFR-1 and FGFR-3 were expressed in most well-differentiated tumor types. FGFR-4, however, was expressed predominantly in aggressive tumor types and the most rapidly proliferative cell lines, indicating that it may promote the progression of these tumors. To specifically determine the function of FGFR-4 in thyroid carcinoma, gain- or loss-of-function studies were performed in cell lines representative of the spectrum of thyroid cancer behavior. Introduction of FGFR-4 resulted in enhanced cell proliferation, an effect that was more pronounced in cell lines derived from aggressive tumors than in those derived from more indolent neoplasms. Moreover, transduction of a dominant-negative FGFR attenuated cell proliferation in the aggressive poorly differentiated cell lines with no appreciable effect in well-differentiated cells. Pharmacologic FGFR-4 tyrosine kinase inhibition resulted in significant proliferation arrest in an aggressive cell line endogenously expressing the receptor. Furthermore, systemic administration of the FGFR tyrosine kinase inhibitor PD173074 resulted in significant inhibition of follicular thyroid carcinoma-derived cell growth in xenografted severe combined immunodeficient mice. These data indicate a role for FGFR-4 in human thyroid cancer cell progression and provide a rationale for FGFR manipulation as a potentially novel therapeutic approach.
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 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".