EXTH-23. ANTISECRETORY FACTOR-MEDIATED LOWERING OF INTERSTITIAL FLUID PRESSURE PRODUCES ANTI-TUMOR ACTIVITY IN GLIOBLASTOMA
| Autor: | Daniele Arosio, Aaron Frantz, William A. Weiss, Valerie M. Weaver, Shirin IIkhanizadeh, Dandan Sun, Anders Persson, Janna K. Mouw, Wen Zhu, Edith Yuan, Yekaterina A. Miroshnikova, Sergey Magnitsky, Hanna Sabelström, Mitchel S. Berger, Aurora Irene Idilli, Supna Saxena, Jason A. Burdick, David A. Quigley, Trenten Fenster |
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| Rok vydání: | 2017 |
| Předmět: |
Antitumor activity
Cancer Research Temozolomide biology urogenital system Chemistry Membrane transport protein business.industry Sodium chemistry.chemical_element medicine.disease nervous system diseases Abstracts Text mining Oncology medicine biology.protein Cancer research Antisecretory factor Neurology (clinical) business Bumetanide medicine.drug Glioblastoma |
| Zdroj: | Neuro-Oncology. 19:vi77-vi77 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/nox168.317 |
| Popis: | Glioblastoma (GBM) is among the most aggressive cancers. Although high interstitial fluid pressure presents a barrier to drug uptake, how mechanical stresses and osmotic changes impact tumor biology remains unclear. We show that inhibition of the sodium-potassium-chloride co-transporter 1 (NKCC1) hindered proliferation and invasion of GBM cells. Compressive pressures actually promoted proliferation of GBM, an effect antagonized by the NKKC1 inhibitor bumetanide, which penetrates poorly into brain, or antisecretory factor, a protein that readily accumulates in brain, and has been used clinically. Antisecretory factor reduced IFP in patient-derived GBM xenografts. Both antisecretory factor and bumetanide inhibited osmotic adaptation of cultured GBM cells. In vivo, antisecretory factor reduced tumor growth, increased uptake of chemotherapeutics, and promoted temozolomide-sensitivity in therapy-resistant GBM xenografts. Thus, antisecretory factor represents a novel strategy to improve outcome in GBM patients. |
| Databáze: | OpenAIRE |
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