Recombinant polio-rhinovirus immunotherapy for recurrent paediatric high-grade glioma: a phase 1b trial.

Background: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric high-grade glioma and has shown promise in adults with recurrent glioblastoma. The poliovirus receptor CD155 is ubiquitously expressed in malignant paediatric brain tumours and is a treatment target in paediatric high-grade glioma.

Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients.

Introduction: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single doses of pegloticase unexpectedly induced antibodies (Ab) that bound to polyethylene glycol (PEG).

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo.

A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H(2)O(2) while depleting urate, offering an in vivo test of the antioxidant hypothesis.

In-vivo gene transfer to the uterine endometrium.

Therapeutic interventions in reproductive biology have relied largely on steroids and antisteroids which act to regulate gene expression in target tissues. Whilst their use has transformed women's lives, few conceptual advances have been made in contraceptive technology, no means identified to improve human implantation and no new strategies developed for the treatment of benign gynaecology. A novel alternative is direct gene transfer to the organ of interest.

Angiogenesis in human dental pulp following orthodontic tooth movement.

The pulpal response to orthodontic force is thought to involve cell damage, inflammation, and wound healing. These situations are likely to be associated with the release of angiogenic growth factors. We therefore investigated human dental pulps to determine if angiogenic changes could be detected after orthodontic force application.