Novel Hydrogel-Mediated Lentiviral Gene Delivery via Intravesical Administration for Bladder Cancer Treatment
Bibliographic record
Abstract
Background/Objectives: Bladder urothelial carcinoma is a frequent malignant tumor of the urinary system, characterized by its high rates of recurrence and resistance to chemotherapy. This study explored the beneficial effects of overexpressing WW domain-containing oxidoreductase (WWOX) in AY-27 cells encapsulated in an injectable gelatin hydrogel for potential therapeutic applications in bladder cancer. Methods: AY-27 cells were genetically transduced with lentiviruses (LV) to overexpress WWOX (LV-WWOX) and subsequently encapsulated in a gelatin hydrogel. The mechanical properties and morphology of the hydrogels were assessed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The therapeutic efficacy of this approach was evaluated using an F344/AY-27 rat orthotopic bladder cancer model, in which the LV-WWOX-hydrogel (H-LV-WWOX) was administered via intravesical instillation. Results: The gelatin hydrogel formulation demonstrated excellent biocompatibility, stability, and controlled release. In a rat orthotopic model, intravesical instillation of H-LV-WWOX significantly enhanced local immune responses, resulting in notable tumor regression. Compared to the sham-treated group, this approach reduced systemic toxicity and improved overall treatment outcomes. The anticancer effect of WWOX can be attributed to its ability to amplify TNF-α-induced reactive oxygen species (ROS) generation. This ROS-mediated pathway leads to enhanced apoptosis and DNA damage in cancer cells, highlighting the potential mechanism through which WWOX exhibits tumor-suppressive activities. Conclusions: These findings support the therapeutic potential of WWOX overexpression in gelatin hydrogels for bladder cancer treatment and warrant further clinical investigation.
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How this classification was reachedexpand
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) | 0.000 | 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".