BPS-001, a complex biologic agent extracted from the medicinal leech (<i>Huridinaria manillensis</i>) for treatment of metastatic castration-resistant prostate cancer.
Bibliographic record
Abstract
209 Background: We established that subcutaneous BPS-001 reduced tumor size and inhibited tumor growth in PC3, LNCaP and 22RV-1 mouse xenografts; and, tumor lHC demonstrated an increase in caspase-3 and decreases in expression of P21, Ki-67 and PCNA. We also showed that BPS-001 reduced PSA expression in both In vitro and in In vivo xenografts (LNCaP and 22RV1). We now demonstrate that BPS-001 inhibits angiogenesis in the xenografts; and, In vitro studies demonstrate that BPS-001 affects expression of adhesion molecules and the androgen receptor. In addition, BPS-001 inhibited tumor growth in a TRAMP allograft model. Methods: CD31 expression was measured using IHC of the previous mouse xenografts. In vitro androgen receptor and adhesion molecule expression were assessed by Western blot. Transplantable TRAMP-C2 mouse prostate cancer in B57CL allografts were grown to 5 mm prior to initiation of treatment. Immune markers in TRAMP allograft tumors were measured by IHC. Results: Mechanistic studies show BPS-001 acts by blocking angiogenesis demonstrated by a > 50% decrease in expression of CD31 in the LNCaP and 22RV-1 xenografts. Furthermore, preliminary toxicology studies show similar efficacy to docetaxel with no weight loss in the longer-term PC3 xenograft study as was observed with docetaxel. Preliminary toxicology studies of BPS-001 also support a favorable toxicity profile, and the therapeutic dose (1-5 mg/Kg, QW or BIW) is well within the margin of safety. Dose limiting toxicity (bleeding) was observed at doses of 20mg/Kg daily. In vitro studies showed BPS-001 decreased expression of both N- and P- cadherins and the androgen receptor. BPS-001 inhibited tumor growth in the TRAMP allograft models. IHC analyses of the TRAMP allograft tumors suggest immunomodulation. Conclusions: BPS-001 exhibits anticancer activity with no observed toxicity in the therapeutic range. Effects of BPS-001 include inhibition of angiogenesis, downregulation of adhesion molecules associated with advanced prostate cancer and inhibition of androgen receptor signaling. Elucidation of the mechanism of action is ongoing.
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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 | 0.001 |
| 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".