Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition

Journal of Neuro-Oncology - Patients diagnosed with primary central nervous system lymphoma (PCNSL) often face dismal outcomes due to the limited availability of therapeutic options. PCNSL cells...     

Molecular genetics of calcium sensing in bone cells

The molecular mechanisms regulating bone remodelling are only partially understood. One of the controversial issues discussed during the past few years is the role that calcium signalling plays in this process and, in particular, in the functioning of the osteoclast. Calcium is involved in the recruitment and activation of osteoclasts and their subsequent detachment from bone. Parathyroid hormone and vitamin D are part of a systemic mechanism regulating calcium availability, storage and disposal. But there are conflicting results suggesting the presence of a local calcium-sensing mechanism in osteoclasts, in osteoblasts or in both. If this system could be characterized, it would be of therapeutic relevance for diseases such as postmenopausal osteoporosis and rheumatoid arthritis. Genetic data, animal models and cell-based assays have not yet been used to their full extent in this area. Here we review the available data and outline possible future strategies.     

Aberrant deltaPKC activation in the spinal cord of Wobbler mouse: a model of motor neuron disease

Protein kinase C (PKC) was suggested to play a role in the pathology of amyotrophic lateral sclerosis (ALS) patients. Activation of PKC delta (deltaPKC) modulates mitochondrially induced apoptosis. The goal of the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease). The level of deltaPKC in the soluble fraction was significantly decreased in the spinal cord of Wobbler mice, which was associated with a significant increase in deltaPKC cleavage. Since caspase-3 is known to cleave deltaPKC, we determined caspase-3 activation in the Wobbler mice spinal cord, immunohistochemically. The results demonstrated intense immunoreactivity for activated caspase-3 in corticospinal tract motor neurons of Wobbler mice spinal cord. We hypothesize from these results that caspase-3 activation cleaves deltaPKC, which in turn promotes an aberrant signal transduction pathway in the Wobbler spinal cord.