Abstract 2536: Therapeutic testing of a novel PKC inhibitor GAP-107B8 on ovarian cancer cells
Bibliographic record
Abstract
Abstract Background: Ovarian cancer is the most fatal gynaecologic disease in the western world. In 2009 in North America, an estimated 23,896 women will develop ovarian cancer and an estimated 15,24050 women will die from this disease. Current treatments are limited to surgery or chemotherapy, but the disease often recurs. Thus, the development of novel cancer therapeutics remains important. The protein kinase C (PKC) family of serine/threonine kinases is involved in cellular proliferation, differentiation, apoptosis and cell polarity. One PKC isoform, PKC iota, has recently been identified as a human oncogene and has been shown to be overexpressed in serous epithelial ovarian cancers and is thus a potential therapeutic target for ovarian cancer. Objective: We have tested a novel PKC inhibitor GAP-107B8 (PharmaGap Inc., Ottawa) in vitro on a panel of nine ovarian cancer cell lines to determine its potential to inhibit cell proliferation, proliferation in soft agar, and migration. Methods: Nine ovarian cancer cell lines were treated with three different concentrations of GAP-107B8 and then screened using high throughput assays to measure the proliferation of cells in adherent and anchorage independent (soft agar) cultures. The ability of cells to migrate in the presence of GAP-107B8 was also determined. Results: We observed significant reduction in cell proliferation in 6 of 9 ovarian cancer cell lines tested, including two cell lines resistant to the standard chemotherapy. GAP-107B8 inhibited cell proliferation by 30% to 79% compared with untreated cells, with more than 50% inhibition in 4 of 7 cell lines. Treatment with GAP-107B caused a reduction in growth in soft agar in 7 of the 9 cell lines tested in vitro. GAP-107B8 inhibited growth in soft agar by 50% to 94% compared with untreated cells, with 80% or greater inhibition in 6 of 7 cell lines. Finally, 5 of 8 cell lines tested showed significant inhibition of mobility following treatment with GAP-107B8. There was 50% or greater inhibition in all 5 cell lines compared with untreated cells. Conclusion: The novel PKC inhibitor GAP-107B8 displays good efficacy in vitro in suppressing several cancer cell characteristics in a variety of ovarian cancer cell lines. Further experiments are underway to investigate the therapeutic potential of GAP-107B8 in xenograft models of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2536.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".