Mr Kevin O'Neill
- London , United Kingdom
- Best at: Brain tumours: benign, malignant and metastatic, neurovascular conditions, spinal conditions
Mr Kevin O’Neill qualified in medicine from St Mary's Hospital Medical School and Imperial College London in 1989, having obtained an intercalated BSc in neuroscience in 1986. He embarked on basic surgical training, obtaining his FRCS in 1994. He embarked on a career in neurosurgery, obtaining his final fellowship in 1998 and becoming a consultant in 1999. He is now head of neurosurgery after specialising in neurovascular and neuro-oncology, where his main research interest is in developing new technologies and treatments.Expertise: Brain tumours: benign, malignant and metastatic, neurovascular conditions: stroke, subarachnoid haemorrhage, aneurysms, arteriovenous malformation (AVM), spinal surgery: disc prolapse, neck, back, arm and leg pain, degenerative spine and tumour surgery, peripheral nerve surgery: tumours and nerve entrapment and injury, brain and central nervous system (CNS) infections. Mr O’Neill’s focus is on brain tumour research. He heads up the brain tumour clinical service at Imperial College and a centre of excellence translation research programme aimed at developing and testing new treatment strategies. He particularly enjoys the application of science and technology to medicine, utilising new technologies and approaches to solving the complexity of disease states of which brain tumours are one of the most complex.
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- neurosurgery - 5
- spine surgery - 3
- oncology - 4
- chemotherapy - 2
brain cancer articles - Impact Factor
- brain tumors - 4
- surgery - 4
Chimeric adeno-associated virus and bacteriophage: a potential targeted gene therapy vector for malignant glioma.
The incipient development of gene therapy for cancer has fuelled its progression from bench to bedside in mere decades. Of all malignancies that exist, gliomas are the largest class of brain tumors, and are renowned for their aggressiveness and resistance to therapy. In order for gene therapy to achieve clinical success, a multitude of barriers ranging from glioma tumor physiology to vector biology must be overcome. Many viral gene delivery systems have been subjected to clinical investigation; however, with highly limited success. In this review, the current progress and challenges of gene therapy for malignant glioma are discussed. Moreover, we highlight the hybrid adeno-associated virus and bacteriophage vector as a potential candidate for targeted gene delivery to brain tumors.
Chemotherapy has made substantial progress in the therapy of systemic cancer, but the pharmacological efficacy is insufficient in the treatment of brain metastases. Fractionated whole brain radiotherapy (WBRT) has been a standard treatment of brain metastases, but provides limited local tumor control and often unsatisfactory clinical results. Stereotactic radiosurgery using Gamma Knife, Linac or Cyberknife has overcome several of these limitations, which has influenced recent treatment recommendations. This present review summarizes the current literature of single session radiosurgery concerning survival and quality of life, specific responses, tumor volumes and numbers, about potential treatment combinations and radioresistant metastases. Gamma Knife and Linac based radiosurgery provide consistent results with a reproducible local tumor control in both single and multiple brain metastases. Ideally minimum doses of ≥18Gy are applied. Reported local control rates were 90-94% for breast cancer metastases and 81-98% for brain metastases of lung cancer. Local tumor control rates after radiosurgery of otherwise radioresistant brain metastases were 73-90% for melanoma and 83-96% for renal cell cancer. Currently, there is a tendency to treat a larger number of brain metastases in a single radiosurgical session, since numerous studies document high local tumor control after radiosurgical treatment of >3 brain metastases. New remote brain metastases are reported in 33-42% after WBRT and in 39-52% after radiosurgery, but while WBRT is generally applied only once, radiosurgery can be used repeatedly for remote recurrences or new metastases after WBRT. Larger metastases (>8-10cc) should be removed surgically, but for smaller metastases Gamma Knife radiosurgery appears to be equally effective as surgical tumor resection (level I evidence). Radiosurgery avoids the impairments in cognition and quality of life that can be a consequence of WBRT (level I evidence). High local efficacy, preservation of cerebral functions, short hospitalization and the option to continue a systemic chemotherapy are factors in favor of a minimally invasive approach with stereotactic radiosurgery.
Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno-associated virus/phage.
Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno-associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor-targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor-bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome-inhibiting drugs and AAVP should be considered for clinical anticancer therapy.
Intra-operative, real-time, three-dimensional ultrasound assisted positioning of catheters in the microdialysis of glial tumours.
Microdialysis allows sampling of the extra cellular fluid of normal and pathological tissues. Accurate positioning of catheters in viable, representative tumour tissue is crucial for the accuracy and effectiveness of the technique. We have performed microdialysis with the aid of intra-operative three-dimensional ultrasonography (3D-US) to guide the placement of catheters in seven patients undergoing resection for supratentorial high-grade astrocytoma. The final position of the catheter tip membrane was confirmed by intra-operative ultrasound scanning. The accuracy of the spatial targeting was validated by pathological examination and the quality of the microdialysate was checked with ultra performance liquid chromatography-mass spectrometry. Our results indicate that intra-operative 3D-US can be used to correctly position catheters for microdialysis and allows adjustment to the catheters, when necessary, prior to the dialysis of viable target tumour tissue.
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