Soluble glypican 3 inhibits the growth of hepatocellular carcinoma
Bibliographic record
Abstract
1516 Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, and the third most common cause of cancer-related mortality. Currently, there are not effective treatments for HCCs that cannot be removed by surgery. Work from our laboratory and from other groups has demonstrated that glypican-3 (GPC3) is expressed by most HCCs (~ 75 %), while it is undetectable in hepatocytes from normal liver and benign liver disease. GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the exocytoplasmic surface of the plasma membrane through a glycosyl-phosphatidylinositol anchor. Experimental evidence accumulated during the last few years indicates that glypicans regulate the activity of several signaling pathways, including those triggered by Wnts, Hedgehogs, BMPs and FGFs. This regulatory activity is based on the ability of glypicans to facilitate or inhibit the interaction of these ligands withtheir signaling receptors. Our laboratory has previously shown that GPC3 promotes the in vitro and in vivo growth of HCC cells by stimulating theWnt signaling pathway. Preliminary evidence suggests that GPC3 facilitates the interaction of Wnt with its receptor Frizzled. Because the growth stimulatory activity of GPC3 in HCC cells requires the attachment of GPC3 to the cell membrane, we havehypothesized that a mutated GPC3 lacking the GPI anchoring domain (soluble GPC3, sGPC3) will inhibit HCC growth. To investigate this hypothesis, Huh7, Li7 and Huh6 HCC cell lines were transduced with alentivirus containingsGPC3 or viruscontrol. We observed that sGPC3-expressing cells have a lower proliferation rate and form fewer colonies in agar than the controls. In addition, sGPC3 significantly inhibited the in vivo growth of HCC cells. Our results suggest that sGPC3 could be used as a therapeutic tool for HCC.
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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) | 0.002 | 0.001 |
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".