Nuclear Glycoprotein A Repetitions Predominant (GARP) Is a Common Trait of Glioblastoma Stem-like Cells and Correlates with Poor Survival in Glioblastoma Patients.

Glioblastoma (GB) is notoriously resistant to therapy. GB genesis and progression are driven by glioblastoma stem-like cells (GSCs). One goal for improving treatment efficacy and patient outcomes is targeting GSCs.

Development of a bleeding scale and hemostasis algorithm in cranial neurosurgery.

Effective hemostasis is crucial in neurosurgery as anatomical and functional considerations reduce tolerance for any bleeding. The classification of bleeding severities is a necessary step to enable neurosurgeons to counteract bleeding during surgery. Even though bleeding scales are used for a variety of surgical specialties, they cannot be transferred to cranial neurosurgery without adaption, and no consensus on the nature of such a classification exists to date.

Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma.

Purpose: Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy.

Methods: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0-2 that were either newly diagnosed (arm A) with a measurable tumor (i.

Long-Term Reduction of Sacroiliac Joint Pain With Peripheral Nerve Stimulation.

Background: We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment.

Objective: To investigate the long-term (up to 4 years) response rate of this novel treatment.

Methods: Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient.

Dual Anti-angiogenic Chemotherapy with Temozolomide and Celecoxib in Selected Patients with Malignant Glioma Not Eligible for Standard Treatment.

Aim: Due to their high rate of neo-angiogenesis, malignant gliomas may qualify for treatment with anti-angiogenic substances. We report on a series of patients with malignant glioma not eligible for standard postoperative combined radiochemotherapy due to decreased health status.

Patients And Methods: A total of nine patients with malignant glioma, postoperatively presenting with a Karnofsky performance score (KPS) below 70, were treated with standalone metronomic low-dose chemotherapy with temozolomide and celecoxib (cyclo-oxygenase-2 inhibitor).

The chemokine receptor CXCR7 influences prognosis in human glioma in an IDH1-dependent manner.

Aims: The chemokine receptor CXCR7 is found on glioma cells and glioma-associated vessels and dependent upon its localisation on tumour or endothelial cells the CXCR7 receptor can mediate glioma cell invasion and tumour angiogenesis. Its expression predicts survival in several types of cancers.

Methods: We immunohistochemically studied the expression of CXCR7 and its ligand SDF1α in a cohort of 354 human patients with glioma.

Technical Note: Treatment of Sacroiliac Joint Pain with Peripheral Nerve Stimulation.

Introduction: Sacroiliac joint (SIJ) pain affects older adults with a prevalence of up to 20% among patients with chronic low back pain. While pain medication, joint blocks and denervation procedures achieve pain relief in most patients, some cases fail to improve. Our goal was to determine the effectiveness of SIJ peripheral nerve stimulation in patients with severe conservative therapy-refractory SIJ pain.

Mutant IDH1 inhibits PI3K/Akt signaling in human glioma.

Background: Recently, isocitrate dehydrogenase 1 (IDH1) was identified as a major participant in glioma pathogenesis. At present, the enzymatic activity of the protein has been the main topic in investigating its physiological function, but its signaling pathway allocation was unsuccessful. Interestingly, proteins regulated by phosphoinositide 3-kinase (PI3K)/Akt signaling, are among the top downregulated genes in gliomas associated with high percentage of IDH1 and IDH2 mutations.

Ligamentum flavum hematomas of the cervical and thoracic spine.

Objective: To report extremely rare cases of ligamentum flavum hematomas in the cervical and thoracic spine. Only six cases of thoracic ligamentum flavum hematomas and three cases of cervical ligamentum flavum hematomas have been reported so far.

Methods: Two patients presented with tetraparesis and one patient presented with radicular pain and paresthesias in the T3 dermatome.

Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients.

APG101 is a glycosylated fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of human IgG1. Administration of APG101 blocks the interaction between CD95 and its cognate ligand CD95L, thereby inhibiting various pathways involved in e.g.

Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor that tends to be resistant to the ionizing radiotherapy used to treat it. Because TGF-β is a modifier of radiation responses, we conducted a preclinical study of the antitumor effects of the TGF-β receptor (TGFβR) I kinase inhibitor LY2109761 in combination with radiotherapy. LY2109761 reduced clonogenicity and increased radiosensitivity in GBM cell lines and cancer stem-like cells, augmenting the tumor growth delay produced by fractionated radiotherapy in a supra-additive manner in vivo.

Correlation of the Ga-68-bombesin analog Ga-68-BZH3 with receptors expression in gliomas as measured by quantitative dynamic positron emission tomography (dPET) and gene arrays.

Purpose: The kinetics of Ga-68-BZH3, a Ga-68-bombesin analog, was compared to molecular biological data obtained from gene arrays in seven patients with a recurrent glioma. The primary aim of this study was the correlation of receptor expression and tracer kinetics.

Procedures: Dynamic positron emission tomography studies were performed and the data were analyzed by a volume-of-interest technique using a two-tissue compartment model as well as a non-compartment model.

Pharmacokinetic studies of ⁶⁸Ga-labeled Bombesin (⁶⁸Ga-BZH₃) and F-18 FDG PET in patients with recurrent gliomas and comparison to grading: preliminary results.

Purpose: Dynamic PET studies with a ⁶⁸Ga-Bombesin analog, the ⁶⁸Ga-BZH₃, were performed in patients with highly suspected recurrent gliomas to investigate the effect of the receptor scintigraphy on tumor grading. Furthermore, dynamic F-18 Fluorodeoxyglucose (FDG) studies were performed for comparison.

Methods: The study consisted of 15 patients with histologically confirmed recurrent gliomas.

Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes.

The current WHO classification of brain tumors defines gliomatosis cerebri (GC) as an extensively infiltrating astrocytic glioma involving at least three cerebral lobes. The relation of GC to diffuse astrocytomas and glioblastoma is uncertain. Due to malignant biological behavior, GC is allotted to WHO grade III.

Continuous low-dose temozolomide and celecoxib in recurrent glioblastoma.

Even after gross tumor resection and combined radiochemotherapy, glioblastomas recur within a few months. Salvage therapy often consists of rechallenging with temozolomide in a dose-intensified schedule. Previously, low-dose metronomic temozolomide in combination with cyclo-oxigenase 2 inhibitors has had a beneficial effect as first-line treatment for glioblastoma.

Far-distant metastases along the CSF pathway of glioblastoma multiforme during continuous low-dose chemotherapy with temozolomide and celecoxib.

Glioblastoma multiforme is the most common and most malignant primary brain tumour. Prognosis after diagnosis remains poor despite recent advances in adjuvant therapy. Treatment of choice is gross surgical resection and combined radio-chemotherapy with temozolomide as chemotherapeutic agent.

Long-term adjuvant administration of temozolomide in patients with glioblastoma multiforme: experience of a single institution.

Purpose: Long-term administration of adjuvant temozolomide is common practice in many institutions, especially when treatment is well tolerated and stable disease is achieved. In this study, we evaluate the feasibility and efficacy of long-term temozolomide in patients with glioblastoma multiforme treated at a single institution.

Methods: One hundred and fourteen patients with newly diagnosed glioblastoma were followed for the course of their disease.

First experiences with low-dose anti-angiogenic treatment in gliomatosis cerebri with signs of angiogenic activity.

Background: Gliomatosis cerebri is a rare primary cerebral tumour entity characterized by diffuse infiltrative growth patterns representing a WHO grade III malignancy. The prognosis is dismal and therapeutical options are still controversial. In contrast to other high-grade gliomas, angiogenesis is thought to be absent in gliomatosis cerebri.

Circulating endothelial progenitor cells in malignant gliomas.

Object: Recent experimental work suggests that circulating endothelial progenitor cells (cEPCs) are recruited to the angiogenic vascular system of malignant gliomas. Consequently, the level of cEPCs has been proposed as a novel biomarker for the diagnosis and monitoring of these lesions. The aim of the present study was to examine the level of cEPCs and the level of EPC mobilizing mediators in the blood of patients with malignant gliomas.

Thoracic intramedullary arachnoid cyst in an infant.

Symptomatic intramedullary arachnoid cysts are rare, especially in children; these lesions are rarely described as a cause of spinal cord compression in this age group. The authors report on an 18-month-old boy who experienced a sudden loss of his ability to stand and walk due to a paraparesis. Magnetic resonance imaging of the spine exhibited a cystic intramedullary lesion at the level of T5-6.

Recurrence pattern in glioblastoma multiforme patients treated with anti-angiogenic chemotherapy.

Purpose: Glioblastoma multiforme is the prototype of an angiogenic tumour. Under experimental conditions, anti-angiogenic therapy strategies lead to an increased invasion. Here we report on the pattern of tumour recurrence in glioblastoma patients treated with an anti-angiogenic chemotherapy.

Clinical evaluation of the safety and efficacy of lumbar cerebrospinal fluid drainage for the treatment of refractory increased intracranial pressure.

Object: Several approaches have been established for the treatment of intracranial hypertension; however, a considerable number of patients remain unresponsive to even aggressive therapeutic strategies. Lumbar CSF drainage has been contraindicated in the setting of increased intracranial pressure (ICP) because of possible cerebral herniation. The authors of this study investigated the efficacy and safety of controlled lumbar CSF drainage in patients suffering from intracranial hypertension following severe traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH).

Interferon-gamma down-regulates NKG2D ligand expression and impairs the NKG2D-mediated cytolysis of MHC class I-deficient melanoma by natural killer cells.

NKG2D operates as an activating receptor on natural killer (NK) cells and costimulates the effector function of alphabeta CD8(+) T cells. Ligands of NKG2D, the MHC class I chain-related (MIC) and UL16 binding protein (ULBP) molecules, are expressed on a variety of human tumors, including melanoma. Recent studies in mice demonstrated that NKG2D mediates tumor immune surveillance, suggesting that antitumor immunity in humans could be enhanced by therapeutic manipulation of NKG2D ligand (NKG2DL) expression.