Long-term safety of gantenerumab in participants with Alzheimer's disease: A phase III, open-label extension study (SCarlet RoAD).

Background: Gantenerumab is a fully human anti-amyloid-β (Aβ) immunoglobulin G1 monoclonal antibody for subcutaneous (SC) administration. The efficacy and safety of low-dose (105 mg or 225 mg) gantenerumab were investigated in SCarlet RoAD (SR; NCT01224106), a Phase III, double-blind (DB), placebo-controlled study in participants with prodromal Alzheimer's disease. Following a pre-planned futility analysis, SR was converted into an open-label extension (OLE) study.

Long-Term Safety of Gantenerumab in Participants with Alzheimer's Disease: A Phase III, Double-Blind, and Open-Label Extension Study (Marguerite RoAD).

Background: Gantenerumab is an anti-amyloid-β immunoglobulin G1 monoclonal antibody for subcutaneous (SC) administration. The efficacy and safety of low-dose (105 mg or 225 mg) gantenerumab were investigated in Marguerite RoAD (MR; NCT02051608), a Phase III, double-blind (DB), placebo-controlled study in participants with mild Alzheimer's disease (AD) dementia. Following a preplanned futility analysis of the SCarlet RoAD study (NCT01224106), MR was converted into an open-label extension (OLE).

Real-time sensing of MAPK signaling in medulloblastoma cells reveals cellular evasion mechanism counteracting dasatinib blockade of ERK activation during invasion.

Aberrantly activated kinase signaling pathways drive invasion and dissemination in medulloblastoma (MB). A majority of tumor-promoting kinase signaling pathways feed into the mitogen-activated protein kinase (MAPK) extracellular regulated kinase (ERK1/2) pathway. The activation status of ERK1/2 during invasion of MB cells is not known and its implication in invasion control unclear.

Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma.

In the Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB), tumor initiation and progression are in part driven by smoothened (SMO) and fibroblast growth factor (FGF)-receptor (FGFR) signaling, respectively. We investigated the impact of the SMO-FGFR crosstalk on tumor growth and invasiveness in MB. We found that FGFR signaling represses GLI1 expression downstream of activated SMO in the SHH MB line DAOY and induces , , and in DAOY and in the group 3 MB line HD-MBO3.

TGF-β Determines the Pro-migratory Potential of bFGF Signaling in Medulloblastoma.

The microenvironment shapes cell behavior and determines metastatic outcomes of tumors. We addressed how microenvironmental cues control tumor cell invasion in pediatric medulloblastoma (MB). We show that bFGF promotes MB tumor cell invasion through FGF receptor (FGFR) in vitro and that blockade of FGFR represses brain tissue infiltration in vivo.

Publisher Correction: Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

MAP4K4 controlled integrin β1 activation and c-Met endocytosis are associated with invasive behavior of medulloblastoma cells.

Local tissue infiltration of Medulloblastoma (MB) tumor cells precedes metastatic disease but little is still known about intrinsic regulation of migration and invasion in these cells. We found that MAP4K4, a pro-migratory Ser/Thr kinase, is overexpressed in 30% of primary MB tumors and that increased expression is particularly associated with the frequently metastatic SHH β subtype. MAP4K4 is a driver of migration and invasion downstream of c-Met, which is transcriptionally up-regulated in SHH MB.

Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model.

Medulloblastoma (MB) is a paediatric cancer of the cerebellum that can develop cerebellar and leptomeningeal metastases. Local brain tissue infiltration, the underlying cause of metastasis and relapse, remains unexplored. We developed a novel approach to investigate tissue infiltration of MB using organotypic cerebellum slice culture (OCSC).

Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice.

Spinal muscular atrophy (SMA) is characterized by motoneuron loss and muscle weakness. However, the structural and functional deficits that lead to the impairment of the neuromuscular system remain poorly defined. By electron microscopy, we previously found that neuromuscular junctions (NMJs) and muscle fibres of the diaphragm are among the earliest affected structures in the severe mouse SMA model.

The craniosacral progression of muscle development influences the emergence of neuromuscular junction alterations in a severe murine model for spinal muscular atrophy.

Aims: As 4-day-old mice of the severe spinal muscular atrophy (SMA) model (dying at 5-8 days) display pronounced neuromuscular changes in the diaphragm but not the soleus muscle, we wanted to gain more insight into the relationship between muscle development and the emergence of pathological changes and additionally to analyse intercostal muscles which are affected in human SMA.

Methods: Structures of muscle fibres and neuromuscular junctions (NMJs) of the diaphragm, intercostal and calf muscles of prenatal (E21) and postnatal (P0 and P4) healthy and SMA mice were analysed by light and transmission electron microscopy. NMJ innervation was studied by whole mount immunofluorescence in diaphragms of P4 mice.