Cancer-Specific Inhibitory Effects of Genetically Engineered Stem Cells Expressing Cytosine Deaminase and Interferon-β Against Choriocarcinoma in Xenografted Metastatic Mouse Models
Why this work is in the frame
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Bibliographic record
Abstract
Cancer treatments using stem cells expressing therapeutic genes have been identified for various types of cancers. In this study, we investigated inhibitory effects of HB1.F3.CD and HB1.F3.CD.IFN-β cells expressing Escherichia coli cytosine deaminase (CD) and human interferon-β (IFN-β) genes in intravenously (i.v.) injected mice with a metastasis model. In this treatment, pro-drug 5-fluorocytosine (5-FC) is converted to cytotoxic drug 5-fluorouracil by hNSCs expressing the CD gene, which inhibits DNA synthesis in cancer cells. Moreover, IFN-β induces apoptosis and reduces the growth of cancer cells. Upon MTT assay, proliferation of choriocarcinoma (JEG-3) cells decreased when co-cultured with hNSCs expressing CD and IFN-β genes. To confirm the cancer-tropic effect of these stem cells, chemoattractant factors (VEGF, CXCR4, and C-kit) secreted from JEG-3 cells were identified by polymerase chain reaction. hNSCs migrate toward JEG-3 cells due to ligand-receptor interactions of these factors. Accordingly, the migration capability of hNSCs toward JEG-3 cells was confirmed using an in vitro Trans-well assay, in vivo subcutaneously (s.c.) injected mice groups (xenograft model), and metastasis model. Intravenously injected hNSCs migrated freely to other organs when compared to s.c. injected hNSCs. Thus, we confirmed the inhibition of lung and ovarian metastasis of choriocarcinoma by i.v. injected HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. Treatment of these stem cells also increased the survival rates of mice. In conclusion, this study showed that metastatic cancer was diminished by genetically engineered hNSCs and noncytotoxic drug 5-FC. This is the first report of the therapeutic potential of i.v. injected hNSCs in a metastasis model; therefore, the results indicate that this stem cell therapy can be used as an alternative novel tool to treat metastatic choriocarcinoma.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 it