Day 2 :
Imperial College London
Time : 09:00-09:25
Nagy Habib is Lead Clinician for the Liver and Pancreatic Unit at Imperial College Healthcare NHS Trust and Academic Head of the Department of Surgery at the Hammersmith Hospital Campus of Imperial College London. Habib is a translational researcher who pioneered the first clinical trial in the use of plasmid and adenovirus for the treatment of liver cancer, as well as the use of plasmid gene therapy in hydrodynamic gene delivery. He was also the Principal Investigator of the world first clinical trials published on the use of adult bone marrow-derived stem cells for the treatment of patients with liver insufficiency and CD34+ cells in patients with stroke. As a clinical scientist he has conducted and published translational research in liver tumours on oncogene, tumour suppressor gene, epigenetic modification, gene therapy, stem cell therapy, and small activating RNA. He was the inventor and was co-author on the first publication to describe the use of radiofrequency energy in devices for liver surgery (Habib 4X), interventional endoscopy (Habib™ EndoHPB and Habib™ EUS-RFA) and interventional radiology (Habib™ VesOpen). He holds a gold award from the Advisory Committee for Clinical Excellence which is given to recognise and reward the exceptional contribution of NHS consultants, over and above that normally expected in a job, to the values and goals of the NHS and to patient care, and he was named as one of Britain’s top surgeons in December 2011 by the Saturday Times Magazine. He was awarded Honorary Professorships by universities in China, Bulgaria, Greece, and Russia. In November 2012 he was awarded Takreem Laureate for his contribution to technology and science.
The preclinical and clinical results of a subset of CD 34+ cells will be presented. The cells were used in three different clinical trials; (i) patients with liver failure; (ii) patients with acute total ischaemic circulation anterior stroke, and; (iii) patients with diabetes complicated by renal transplant. Safety and efficacy aspects of the studies will be discussed and also a new technique to increase efficacy of stem cells using small activating RNA1.
University College London
Time : 09:25-09:50
Gordon Blunn is a bioengineer at the Institute of Orthopaedics and Musculoskeletal Science at University College London; he is based at the Royal National Orthopaedic Hospital. He has been at this Institution for 25 years and during this period of time he has investigated the use of the fixation of implants to the skeleton. He has translated a number of novel treatments and designs into patients, which has enhanced implant fixation. He is currently the president of the British Orthopaedic Research Society.
Orthopaedic implants are extremely successful however in some instances fixation to the surrounding bone is problematic. In patients with bone cancer a massive prosthesis is used to replace the diseased bone. At the same time patients receive chemotherapy to treat and stop the spread of the cancer. In these cases the loosening rate is high, which leads to prostheses being removed and revised. Bone cancer occurs in young patients and these patients may be faced with numerous revision operations throughout their life, therefore, enhancing fixation of these implants is important. We have shown that augmentation with materials such as hydroxyapatite does reduce loosening but there still remains a number of cases where loosening occurs. The aims of this study were to use mesenchymal stem cells to enhance implant fixation to the bone surface (osteointegration).We carried out an investigation on femoral bone defects in rats, which showed that incorporating mesenchymal stem cells within fibrin enhanced bone formation even in those animals given a chemotherapy regime similar to that received by humans. Fibrin glue was chosen as the carrier as this could be sprayed onto the surface of the implant and formed a stem cell layer. Stem cells survived and proliferated within the fibrin glue and they remained viable after spraying the cells onto the implant surface. In an ovine model autologous stem cells were sprayed onto the surface of the implant at a concentration of 1 million cells per ml. After 6 months increased osteointegration of over 100% was measured. Increasing the number of the cells within the glue up to 10 million per ml had a significant affect. Using cells that had been differentiated into osteoblasts also increase osteointegration.However, using autologous mesenchymal stem cells resulted in little new bone formation and in osteoclastic resorption.
Thomas Jefferson University
Keynote: Breast cancer stem cell function: Molecular genetic determinants and the cell fate determination pathway
Time : 9:50-10:25
Richard Pestell (MD, PhD, MBA, FRACP, FACP, MBBS) is a leader in the global cancer community. He has galvanized international teams to fight cancer, has >600 published works, and multiple patents in cancer diagnostics and treatment including light-activated gene therapy. He founded companies (ProstaGene, AAAPhoenix) and Institutes, led cancer not–for-profits and directed two US Cancer Centers (Lombardi Comprehensive Cancer Center, and the Sidney Kimmel Cancer Center at Thomas Jefferson University. He was most recently Executive Vice President Thomas Jefferson University in Philadelphia, USA. His work in breast and prostate cancer and the cell cycle is highly cited (>41,500 citations, H index >100).
A subpopulation of cells have been identified within tumors referred to as tumor initiating cells (BTIC) (cancer stem cells). These cells have been hypothesized to contribute to therapy resistance and tumor recurrence. Contributions to the understanding of the molecular genetic drivers of TIC using multigenic tissue specific temporally and spatially inducible transgenic mice have shown endogenous mammary tumor stem cells expansion is maintained by endogenous c-Jun, and NFkB. The cell cycle control protein p21CIP1 restrains, and cyclin D1 promotes, TIC populations respectively and Notch requires cyclin D1 for BTIC expansion. \\r\\nRecent studies from this laboratory have shown the RDGN (retinal determination gene network) is a dominant regulator of BTIC. In Drosophila Melanogaster, the Retinal Determination Gene Network (RDGN) determines organismal cell fate. The RDGN human homologues include DACH, EYA, Six, and Toy. We showed the RDGN (DACH1, and Eya) governs BTIC. The Drosophila Eyes Absent Homologue 1 (EYA1) is a component of the retinal determination gene network and serves as an H2AX phosphatase. EYA1 enhanced breast tumor growth in mice in vivo, requiring the phosphatase domain. EYA1-dependent induction of breast cancer cell proliferation and mammosphere formation was cyclin D1-dependent. The induction of cellular proliferation and cyclin D1 abundance, but not apoptosis, was dependent upon the EYA1 phosphatase domain. The relative proportion of cells, with characteristics of breast tumor stem cells were assessed in mice with targeted deletion of Dach1 in the mammary gland. The function of the RDGN and the interface with the cell cycle control genes in BTIC will be discussed\\r\\n