Abstract 672: PBI-1402, a first-in-class erythropoiesis regulating agent, inhibits tumor growth and metastasis of murine mastocytoma and does not overshoot hemoglobin: Comparison with erythropoietin
Bibliographic record
Abstract
Abstract BACKGROUND: PBI-1402 reduces the need for transfusion and increases hemoglobin (Hb) level and red blood cell count (RBC) in chemotherapy-induced anemia (CIA) by a mechanism of action distinct from erythropoietin (EPO). AIM: The objective was to compare the effect of PBI-1402 and EPO on modulation of tumor growth. METHODS: The effect of PBI-1402 (200 mg/kg, oral, once a day) or EPO (200 or 2000 U/kg, s.c. injection, twice a week) was studied in a subcutaneous P815 mastocytoma model. P815 cells express both PBI-1402 and EPO receptors. Tumor growth, metastasis, serum nitric oxide (NO) and hematocrit (Ht) were assessed. RESULTS: P815 tumor growth is rapid and metastasizes to the liver. Inflammation is also associated with P815 tumor growth. PBI-1402 significantly reduced tumor growth (T/C=37%) and invasion as demonstrated by a 33% reduction of mice with liver metastasis. In comparison, EPO had no effect (200 U/kg, equivalent dose used in CKD treatment). However, high dose EPO (2000 U/kg, equivalent dose used in human cancer treatment) exacerbated tumor growth (T/C: 135%). Both doses of EPO induced a significant increase in the percentage of mice with liver metastasis (2X, 200 U/kg, and 3X, 2000 U/kg) compared to control. PBI-1402 treatment had no effect on NO and did not overshoot normal hematocrit. However, treatment with high dose EPO significantly increased NO and Ht levels (Table 1). CONCLUSION: These results suggest that oral treatment with PBI-1402 may inhibit growth and metastasis of cancer cells. As an important safety feature, PBI-1402 does not induce overshoot of hemoglobin. In contrast to EPO, PBI-1402 may offer the advantage of reducing tumor growth and metastasis while preventing anemia induced by chemotherapy. In conclusion, PBI-1402 has the potential to be a safe erythropoiesis-regulating agent useful in treating anemia in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 672. doi:10.1158/1538-7445.AM2011-672
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".