P08.04 Antitumor effects of medroxyprogesterone on glial tumor growth in vitro and in vivo and an unexpected contribution of PI3Kinase on anti-invasive effects of steroids
Bibliographic record
Abstract
INTRODUCTION: Among the cytosolic sex steroid receptors, progesterone receptor is the one which most significantly associated with the tumor grade in glial neoplasms. Progesterone gradually increases from the first until the last day of pregnancy and reaches 200-fold of its prepartum luteal concentrations. Glial tumors manifest more during the first trimester yet their incidence become lesser at the last trimester of gestation. Additionally; in opposite to meningiomas, women gender, being everparous and progesterone-containing hormone replacement therapy (HRT) reduces risk of glial tumors. Medroxyprogesterone acetate (MPA) is a widely used 17-OH-progesterone for contraception and HRT and strongly activates progesterone receptor and to a lesser extent, glucocorticoid receptor (GR). Antiedema agents like dexamethasone (Dex) bind to the GR, which were also shown to reduce glial tumor invasiveness. MATERIALS AND METHODS: In this investigation, we studied in vitro antitumor effects of MPA on human glial tumor cell lines (U87 and U251) and the contribution of PI3-Kinase pathway on the anti-invasive efficacies of MPA and Dex. We also studied in vivo efficacy of MPA on C6 glioma implanted into Wistar rat brains. RESULTS: At low doses, (3,25 to 16,3 μM) MPA slightly and insignificantly induced growth of U87 and U251 human glioblastoma cells in monolayer cultures. At doses higher than 52 μM, cell numbers drastically reduced and few cells survived at 104 μM. In 3D-spheroid cultures maintained in semisolid type-I collagen, MPA and Dex dose-dependently reduced tumor invasion even at low dosages. Unexpectedly, PI3-Kinase inhibitors LY294002 and wortmannin at low dosages hindered anti-invasive effects of both MPA and Dex. PI3-Kinase pathway is mostly pro-tumorigenic, yet few studies also demonstrated that this pathway may also transmit antitumor signals. To the best of our knowledge, this is the first study which showed that benefits of antiedema steroids in glial tumors may occur via PI3Kinase. In Wistar rats inoculated with C6 glioma, 50 mg/kg/day MPA reduced tumor volume by about 50 percent in 3 weeks. CONCLUSIONS: Considering the high safety of MPA and also that blood progesterone levels up to 160 μM are tolerable in human, these current investigations warrant further study.
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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) | 0.000 | 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) | 0.005 | 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".