Re-Use of Established Drugs for Anti-Metastatic Indications.

Most patients that die from cancer do not die due to the primary tumor but due to the development of metastases. However, there is currently still no drug on the market that specifically addresses and inhibits metastasis formation. This lack was, in the past, largely due to the lack of appropriate screening models, but recent developments have established such models and have provided evidence that tumor cell migration works as a surrogate for metastasis formation.

Anti-metastatics: an overview of drug candidates in current pipelines.

As the number of novel drugs that have entered the market in oncology has slowed in recent years, there has been a dramatic shift towards new therapeutic approaches. The majority of cancer patients die from metastasis formation, which has prompted the pharmaceutical industry to begin to investigate a new class of agents: anti-metastatics. This review provides an overview of the targets, mechanisms of action, and drug substances currently in the pharma pipeline to inhibit tumor cell migration and metastasis formation.

Rapid β-amyloid deposition and cognitive impairment after cholinergic denervation in APP/PS1 mice.

Although extensive evidence supports the role of β-amyloid (Aβ) in Alzheimer disease (AD), the neurotoxic mechanisms underlying AD pathogenesis are not understood. On the other hand, neuronal loss is the pathologic feature that best correlates with cognitive impairment. We hypothesized that cholinergic neurodegeneration may lead to Aβ deposition and tested this by inducing selective cholinergic lesions in APPswe/PS1dE9 mice with murine p75 saporin (mu p75-SAP).

Four-dimensional microglia response to anti-Aβ treatment in APP/PS1xCX3CR1/GFP mice.

Senile plaques, mainly composed of amyloid-β (Aβ), are a major hallmark of Alzheimer disease (AD), and immunotherapy is a leading therapeutic approach for Aβ clearance. Although the ultimate mechanisms for Aβ clearance are not well known, characteristic microglia clusters are observed in the surround of senile plaques, and are implicated both in the elimination of Aβ as well as the deleterious inflammatory effects observed in AD patients after active immunization. Therefore, analyzing the direct effect of immunotherapy on microglia, using longitudinal in vivo multiphoton microscopy can provide important information regarding the role of microglia in immunotherapy.

Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid β peptide (Aβ) as senile plaques in the brain is the pathological hallmark of AD, but oligomeric, soluble forms of Aβ have been implicated as the synaptotoxic component. The apolipoprotein E ε 4 (apoE ε4) allele is known to be a genetic risk factor for developing AD.