Abstract 4038: Role of the Rho-GTPase CDC42 in glioma migration
Bibliographic record
Abstract
Abstract Introduction: Malignant astrocytoma is a highly proliferative and invasive neoplasm that infiltrates diffusely into regions of normal brain rendering total surgical extirpation impossible and effective local radiation therapy difficult. Conventional chemotherapy frequently fails because most agents administered systemically will not cross the blood-brain barrier. Despite recent reports which have shown a 2-month survival advantage when adjuvant temozolomide chemotherapy is used for glioblastoma multiforme, death ensues in most cases within 2 years of diagnosis. For truly significant advances to be made in the treatment of patients with malignant astrocytoma, we must develop a greater understanding of the basic biology of these neoplasms. PURPOSE: The aim of this study is to examine a key pathway involving the Rho-GTPase family of proteins that regulates glioma cell migration from the tumor mass into normal brain tissue. One of the Rho-GTPase family proteins, CDC42 is the major regulator of cell polarity. It plays a crucial role in controlling the direction of cell migration by determining the cell membrane localization of lamellipodia, and by moving the microtubule-organizing center and Golgi apparatus in front of the nucleus and towards the leading edge of the cell. However, there have been few reports on the role of CDC42 in human astrocytomas. METHOD: In order to examine the role of CDC42 in glioblastoma, we generated stable doxycycline (DOX) inducible cell lines expressing wild type (WT) -, constitutively active (CA) -, and dominant negative (DN) -CDC42. Cell viability, migration, and invasion assays were performed using the cell lines. We also used orthotopic xenograft mouse models and evaluated the survival by Kaplan-Meier analysis. RESULTS: Administration of DOX induced the expression of CA-CDC42 and demonstrated significantly increased migration and invasion properties compared to WT and DN-CDC42. Furthermore, CA-CDC42 bearing mice with DOX treatment had significantly decreased survival compared to WT and DN with DOX. CONCLUSION: Our results demonstrated that CA-CDC42 enhances the astrocytoma invasion and migration. Furthermore, CA-CDC42 increased the size of implanted tumor in the murine brain leading to early mortality. We concluded that CA-CDC42 plays an important role for astrocytoma malignancy. Citation Format: Hidehiro Okura, Brian J. Golbourn, Amanda J. Luck, Christian A. Smith, James T. Rutka. Role of the Rho-GTPase CDC42 in glioma migration. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4038. doi:10.1158/1538-7445.AM2015-4038
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".