Tumor-specific and Photodependent Cytotoxicity of Hypericin in the Human LNCaP Prostate Tumor Model
Bibliographic record
Abstract
Hypericin (HYP) has been reported to have photodependent cytotoxic activity in a variety of cancer cell lines. However, this activity has yet to be rigorously tested in vivo in tumor models. In this study LNCaP, PC-3 and DU-145 cells were used to test the cytotoxic effects of HYP in vitro, precursory to an in vivo study designed to investigate the effects of HYP in an established murine model for prostate cancer. Specifically, the model used employs immunocompromised nude mice bearing the LNCaP solid tumor xenograft. In vitro cytotoxicity experiments indicated that the dose causing 50% lethality for HYP in LNCaP, PC-3 and DU-145 cells were 2.07, 2.15 and 2.23 microM, respectively, following irradiation with red light (590 nm) for 30 min at a fluence rate of 0.1 J/cm2/s. Cells treated with HYP in the absence of photoirradiation showed no signs of cytotoxicity. A tissue distribution study was also carried out using the LNCaP solid tumor model to determine whether or not HYP is distributed to the target tissue. HYP was broadly distributed in tissues studied, including LNCaP tumor xenograft tissue. Furthermore, tumor tissue eliminated HYP at a slower rate than any of the other tissues examined. Interestingly, HYP levels were maintained in serum 24 h after oral administration (5 mg/kg dose). A pilot study designed to examine the efficacy of HYP treatment in nude mice bearing LNCaP tumors conducted over 28 days suggested that HYP, in combination with photoirradiation, inhibits both tumor growth and the elevation of prostate-specific antigen levels. Although the results reported for the current studies are preliminary they do provide evidence for an application of HYP PDT to prostate cancer which warrants further 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 | 0.001 | 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 | 0.001 |
| 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".