Journal of internal medicine
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In this review, we discuss the genetic factors in both the aetiology and treatment of ischaemic stroke. We discuss candidate gene association studies, family linkage studies and the more recent whole genome association studies and whole genome expression studies. We also briefly discuss genetic testing for stroke risk and genetic analysis of treatment complications.
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Microvessels and neurons respond rapidly and simultaneously in focal regions of ischaemic injury in such a way as to suggest that the responses could be coordinated. The ability of neurons to modulate cerebral blood flow in regions of activation results from neurovascular coupling. But little is known about the microvessel-to-neuron direction of the relationship. ⋯ The failure, so far, of clinical trials of neuron protectant agents to achieve detectable tissue salvage could be explained by the vulnerability (and lack of protection) of essential components of the 'unit'. This presentation summarizes evidence and thoughts on this topic. These support the need to understand component interactions within the neurovascular unit.
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Small interfering RNA (siRNA) technology holds great promise as a therapeutic intervention for targeted gene silencing in cancer and other diseases. However, in vivo systemic delivery of siRNA-based therapeutics to tumour tissues/cells remains a challenge. The major limitations against the use of siRNA as a therapeutic tool are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. ⋯ Recently, our laboratories described the use of neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine based nanoliposomes in murine tumour models. We found this approach to be safe and 10- and 30-fold more effective than cationic liposomes and naked siRNA, respectively, for systemic delivery of siRNA into tumour tissues. Here, we review potential approaches for systemic delivery of siRNA for cancer therapy.
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Myopathy is a known side effect of statins, but neurotoxicity is not. Two studies reported that statins and amyotrophic lateral sclerosis (ALS) appear together more than expected amongst adverse events in overlapping surveillance databases. ⋯ There was no similar increase in ALS incidence. The initial signals of a strong association from drug surveillance systems should now be discounted, but not disregarded.
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As our understanding of the molecular mechanisms governing natural killer (NK) cell activity increases, their potential in cancer immunotherapy is growing increasingly prominent. This review analyses the currently available preclinical and clinical data regarding NK cell-based immunotherapeutic approaches in cancer starting from a historical background and an overview of molecular mechanisms taking part in NK cell responses. The status of NK cells in cancer patients, currently investigated clinical applications such as in vivo modulation of NK cell activity, ex vivo purification/expansion and adoptive transfer as well as future possibilities such as genetic modifications are discussed in detail.