Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma

The phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway is critical in glioblastomas. Loss of PTEN, a negative regulator of the PI3K pathway or activated PI3K/Akt pathway that drive increased proliferation, survival, neovascularization, glycolysis, and invasion is found in 70%–80% of malignant gliomas. Thus, PI3K is an attractive therapeutic target for malignant glioma. We report that a new irreversible PI3K inhibitor, PX-866, shows potent inhibitory effects on the PI3K/Akt signaling pathway in glioblastoma. PX-866 did not induce any apoptosis in glioma cells; however, an increase in autophagy was observed. PX-866 inhibited the invasive and angiogenic capabilities of cultured glioblastoma cells. In vivo, PX-866 inhibited subcutaneous tumor growth and increased the median survival time of animals with intracranial tumors. We also assessed the potential of proton magnetic resonance spectroscopy (MRS) as a noninvasive method to monitor response to PX-866. Our findings show that PX-866 treatment causes a drop in the MRS-detectable choline-to-NAA, ratio and identify this partial normalization of the tumor metabolic profile as a biomarker of molecular drug action. Our studies affirm that the PI3K pathway is a highly specific molecular target for therapies for glioblastoma and other cancers with aberrant PI3K/PTEN expression.     

Über den Einfluss des Manganchlorürs auf die Anaphylaxie

Ohne Zusammenfassung     

Indikationen der Lupustherapie nach ihrem gegenwärtigen Stande

Ohne ZusammenfassungHiezu 24 Abbildungen im Texte.     

Über Vergleichende Untersuchungen mit dem Pulsresonator und dem Elektrokardiographen

Ohne ZusammenfassungHerr Prof.Mosler, Herr Ing.Rost und Frl.Steingötter haben uns bei unseren Untersuchungen in dankenswerter Weise unterstützt.     

Zur Pathogenese der Kälteurticaria

Ohne Zusammenfassung