Silencing of protein kinase D2 induces glioma cell senescence via p53-dependent and -independent pathways.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive tumor of the central nervous system with a dismal prognosis for affected patients. Aberrant protein kinase C (PKC) signaling has been implicated in gliomagenesis, and a member of the PKC-activated protein kinase D (PRKD) family, PRKD2, was identified as mediator of GBM growth in vitro and in vivo. METHODS: The outcome of PRKD2 silencing and pharmacological inhibition on glioma cell proliferation was established with different glioma cell lines. Western blotting, senescence assays, co-immunoprecipitation, fluorescence activated cell sorting, quantitative PCR, and immunofluorescence microscopy were utilized to analyze downstream signaling. RESULTS: RNA-interference (21-mer siRNA) and pharmacological inhibition (CRT0066101) of PRKD2 profoundly inhibited proliferation of p53(wt) (U87MG, A172, and primary GBM2), and p53(mut) (GM133, T98G, U251, and primary Gli25) glioma cells. In a xenograft experiment, PRKD2 silencing significantly delayed tumor growth of U87MG cells. PRKD2 silencing in p53(wt) and p53(mut) cells was associated with typical hallmarks of senescence and cell cycle arrest in G1. Attenuated AKT/PKB phosphorylation in response to PRKD2 silencing was a common observation made in p53(wt) and p53(mut) GBM cells. PRKD2 knockdown in p53(wt) cells induced upregulation of p53, p21, and p27 expression, decreased phosphorylation of CDK2 and/or CDK4, hypophosphorylation of retinoblastoma protein (pRb), and reduced transcription of E2F1. In p53(mut) GM133 and primary Gli25 cells, PRKD2 silencing increased p27 and p15 and reduced E2F1 transcription but did not affect pRb phosphorylation. CONCLUSIONS: PRKD2 silencing induces glioma cell senescence via p53-dependent and -independent pathways.

Acute subdural hematoma without subarachnoid hemorrhage or intraparenchymal hematoma caused by rupture of a posterior communicating artery aneurysm: case report and review of the literature.

BACKGROUND: Acute subdural hematoma without subarachnoid hemorrhage or intraparenchymal hematoma is rare. CASE REPORT: We report on a 47-year-old women without previous trauma who presented with an acute subdural hematoma without subarachnoid hemorrhage. The hematoma was evacuated immediately. Further evaluation with a cerebral four-vessel angiography revealed a left-sided posterior communicating artery aneurysm that was occluded by endovascular embolization. The patient recovered without neurological deficit. CONCLUSIONS: Ruptured intracranial aneurysm should be considered as a cause of nontraumatic subdural hematoma. Immediate subdural hematoma removal after aneurysm coiling can be performed in such patients, even those in poor neurological condition.

An uncommon case of Idiopathic Intracranial Hypertension with diagnostic pitfalls.

We report on an unusual case of Idiopathic Intracranial Hypertension (IIH) in a woman of normal weight. Papilledema and increased intracranial pressure are symptoms of cerebral venous sinus thrombosis or idiopathic intrancranial hypertension. Because of the different treatment strategies, it is important to keep these two diseases separate. We show that the use of different imaging methods is an important tool in obtaining an effective diagnosis.