Transcriptional Profiling of Circulating Malignant Cells Isolated From an Animal Model of Uveal Melanoma
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 4169 Purpose: Uveal melanoma is the most common intraocular tumor in adults and is exclusively disseminated via a haematogenous route in order to form metastasis. The aim of this study is to measure the transcriptional profiles of human uveal melanoma cells isolated and cultured from the intraocular primary tumor, circulating malignant cells and metastasic locations. Materials and Methods: Human single-spotted 19k microarrays and universal human reference RNA were used to measure the differences between cultured cells isolated from various locations in an immunosuppressed rabbit model of uveal melanoma. Cells were isolated at the time of sacrifice from intraocular, peripheral blood and metastasis. RNA was then extracted from each sample and subjected to transcriptional profiling analysis. Results were compared to the transcriptional profiles previously obtained from the original 92.1 cell line injected into the eye of the rabbits. Results: Statistical analysis using an ANOVA cut off of 0.05 revealed 3123 transcripts that were modulated between the re-cultured cells from each location and the original 92.1 cell line. 207 of those transcripts had at least a two fold increase or decrease. Included in the transcripts of interest that were up regulated in the circulating malignant cells were Septin 7, Alpha Kinase 3, and Insulin receptor substrate 2. Melanoma specific markers such as Melan A were included in the group of transcripts that were down regulated. Conclusion: For the first time we describe proteins that are significantly up or down regulated between primary, circulating malignant cells and metastasis in uveal melanoma. These changes included transcription factors, ribosomal proteins, and melanoma specific markers. Moreover, cells that were re-cultured after isolation from blood maintained these significant changes. These changes allow us to investigate the expression patterns that uveal melanoma cells may require to survive through circulation until the time of implantation at a distant organ. Future work will investigate the role of these factors in the survival of cells in circulation and their role in metastasis.
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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 | 0.000 |
| 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".