Response of bladder cancer cells and xenografts to treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and gemcitabine
Bibliographic record
Abstract
A53 Introduction: Approximately 80% of newly diagnosed bladder cancers are superficial transitional cell carcinomas (TCC), which usually recur and can progress to higher stages after surgical resection. Current topical (intravesical) therapeutics used to prevent recurrence have significant limitations. TRAIL induces apoptosis selectively in variety of tumor cells, but not in normal cells. Moreover, in combination with other DNA-damaging agents, TRAIL has synergistic antitumor activity. Combination therapy with TRAIL and gemcitabine has not been explored. We hypothesize that TRAIL and gemcitabine will have an additive effect on TCC. Methods: Gemcitabine (Eli Lilly) and TRAIL/Apo2L (PeproTech Inc.) were dissolved in saline. Human TCC cell lines as monolayers in appropriate media under standard conditions (37°C, 5% CO2) were tested. Cells in log phase growth were seeded in 96-well microtiter (5 x 104 cells/well) or in 60-mm culture plates (5 x 105). After overnight incubation, the medium was replaced with one containing gemcitabine at a concentration of 10-8 to 10-4M (without or with 300 ng/mL TRAIL). After 4-hr incubation at 37oC, the medium containing the therapeutic agents was replaced with fresh drug-free medium. Cells were cultured for further 72 hrs. Cytotoxicity was analyzed by standard MTT of the 96-well microtiter plates and expression of apoptotic proteins determined by SDS-PAGE and western blot analysis on whole-cell lysates from 60-mm plates. Athymic nude mice were injected subcutaneously with human TCC cells (UMUC14) at their left flank. When tumors reached ~3 mm in diameter, animals (4 per group) were treated with a), TRAIL intratumor injection (i.t.); b), TRAIL intraperitoneal injection (i.p.); c), gemcitabine i.p.; and d), saline i.t. (control). The dose of TRAIL was 20 µg daily, and that of gemcitabine was 2 mg twice weekly, for a total of 6 times. Results: The IC50 for gemcitabine was 1 µM for RT112. Both CRL1472 and UMUC14 cell lines were less sensitive with IC50 >10 µM. In the presence of TRAIL there was a marked increase (p
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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) | 0.001 | 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 | 0.001 |
| 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".