Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-1 | Award Amount: 8.10M | Year: 2013
Colorectal cancer (CRC) is the 3rd most common cancer in Europe, and with approximately 200,000 deaths per year, it remains the 2nd most common cause of cancer death. More than half of all CRC patients develop distant metastases and have 5-year overall survival (OS) of less than 5% because of ineffective treatments. Increased understanding of cancer biology, coupled with the implementation of omics-based approaches, has revealed that cancer must be considered a heterogeneous disease. Historically, one-size-fits-all approaches have been standard practice in CRC treatment, but with the increased understanding of the molecular/genetic heterogeneity of CRC, it is clear that novel treatments must be developed and tested in selected subgroups to maximize the benefit of these new developments. MErCuRIC is a multicentre phase Ib/II clinical trial which will assess a novel therapeutic strategy (combined treatment of a MEK inhibitor PD-0325901 with a MET inhibitor PF-02341066) to combat metastasis, improve survival and change current clinical practice for CRC patients with KRAS mutant (MT) and KRAS wild type (WT) (with aberrant c-MET) tumours. The consortium will go beyond the current state-of-the-art by (i) employing a novel treatment strategy targeting the biology of the disease and by (ii) using next generation sequencing (NGS) and xenopatients to identify CRC patient subgroups who will maximally benefit from this novel treatment strategy.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.99M | Year: 2015
Type 2 diabetes will affect >500 million adults by 2040 and its secondary complications will generate enormous socioeconomic costs - in particular, diabetic kidney disease (DKD), which is already the most common cause of chronic kidney disease. DKD is associated with greatly increased mortality and frequently progresses to end stage renal failure. Pharmacotherapy, dialysis and transplantation represent the mainstay treatments for DKD but are costly and provide only limited protection against adverse outcomes. Mesenchymal Stromal Cell (MSC) therapy is a promising approach to halting the progression of DKD toward end-stage renal failure and may also have ancillary benefits in Type 2 diabetes. In preliminary research, we have demonstrated that a single dose of MSC simultaneously improves kidney function (glomerular filtration rate and albuminuria) as well as hyperglycaemia in animals with DKD. NEPHSTROM will conduct a multi-centre, placebo-controlled clinical trial of a novel MSC therapy for stabilization of progressive DKD, leading to superior clinical outcomes and long-term socioeconomic benefit. A key enabler for this trial is a novel MSC population (CD362\MSC, trade name ORBCEL-M) which delivers higher purity and improved characterisation compared to conventional plastic-adherent MSC. The NEPHSTROM Phase 1b/2a clinical trial will investigate the safety, tolerability and preliminary efficacy of a single intravenous infusion of allogeneic ORBCEL-M versus placebo in adults with progressive DKD. NEPHSTROM investigators will also determine the bio-distribution, mechanisms of action, immunological effects and economic impacts associated with ORBCEL-M therapy for DKD. This research will critically inform the optimal design of subsequent Phase 3 trials of ORBCEL-M. Stabilising progressive DKD through NEPHSTROMs next-generation MSC therapy will reduce the high all-cause mortality and end-stage renal failure risk in people with this chronic non-communicable disease
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-4.2-1 | Award Amount: 7.38M | Year: 2009
HYPOTHESIS: Early inhalation of Budesonide (BS) reduces the absolute risk of developing bronchopulmonary dysplasia (BPD) or death in preterm infants born between 23 and 27 weeks gestational age (GA) by 10%. PRIMARY OBJECTIVE: Survival without BPD at 36 weeks GA. SECONDARY OBJECTIVES: (1) neurodevelopment at a corrected age of 18-22 months; (2) adverse treatment effects; (3) mortality at 36 weeks GA; (4) BPD incidence at 36 weeks GA; (5) duration of positive pressure respiratory support or supplemental oxygen; (6) pharmacokinetic-pharamacodynamic analyses. RATIONALE: Inflammation is central to the development of BPD. Corticosteroids (CS) have antiinflammatory properties and early inhalation of CS may allow for beneficial local effects on the pulmonary system with a lower risk of undesirable systemic side effects. STUDY DESIGN: Randomised placebo-controlled, multi-centre clinical trial and genetic/pharmacogenetic substudy. RESEARCH PLAN: Within 2 years 850 infants of 23-27 weeks GA will be randomised during the first 12 hours of life to BS or placebo to prevent BPD. Study drugs will be administered via Aerochamber and continued until infants are either off supplementary oxygen and positive pressure support or have reached a GA of 32 0/7 weeks regardless of ventilatory status. Study patients will be followed and neurodevelopmental outcomes will be assessed at a corrected age of 18-22 months. CLINICAL SIGNIFICANCE: BPD contributes to the mortality of preterm infants and is associated with impaired neurosensory development and an increased risk of pulmonary morbidity in adolescence and young adulthood. Systemic CS are effective in preventing BPD, but their use is practically prohibited given their adverse effects on neurodevelopment. Early inhalation of CS has been shown to be associated with secondary pulmonary benefits, but its effect on survival without BPD and on neurodevelopment remains unclear.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.1.1-2 | Award Amount: 7.84M | Year: 2011
The purpose of the project is to identify genome-based biomarkers for use in clinical practice to individualise treatment of epilepsy, and stratify patients for clinical trials, aiming to avoid chronicity, prevent relapse and reduce adverse drug reactions (ADRs). The need for improved treatments in epilepsy is undoubted. Epilepsy is affects 50,000,000 people of all ages worldwide. Epilepsy is serious, increasing morbidity across all aspects of life, including a high risk of premature mortality. Over 20 antiepileptic drugs (AEDs) are licenced for its treatment. Seizures can be effectively controlled by AEDs in ~70% of people. Control of seizures leads to risk reduction for most of consequences of epilepsy, improves quality of life, permits social re-integration and leads to direct economic benefits. However, in 30% of patients, currently-available AEDs do not control seizures recurrent seizures threaten life and impair its quality in these patients, and account for much of the 15.5 billion annual cost of epilepsy in the EU alone; there is currently no way to predict which patients will not respond to any or all AEDs; even in the 70% who do respond, only 47% respond to the first AED whilst the correct drug is being sought, risks from seizures continue we need to be able to predict the right drug for an individual from the outset; unrelated to responder status, AEDs can cause serious ADRs a biomarker exists for only one ADR; there is a clear need for novel means of discovery of new AEDs existing AEDs are anti-seizure drugs, not disease-modifying drugs. We will use genome-wide analyses, including next-generation sequencing, in large, well-phenotyped patient cohorts to identify genome-based biomarkers, to improve use of current AEDs and identify new therapy targets. SMEs, which are central to this project, will be able to take the data forward for development of clinical tests; data will also be invaluable for industry seeking to develop new treatments.
Queen's University of Belfast and Belfast Health And Social Care Trust | Date: 2013-06-13
The present invention relates to a method for a method for predicting the development of renal dysfunction in a subject following physical trauma, hypotension, sepsis and/or septic shock syndrome, wherein the method comprises the steps of: a. determining the level of an anti-inflammatory cytokine present in a sample taken from the subject after physical trauma, after a hypotensive event, after sepsis, and/or after septic shock syndrome; b. predicting the development in the subject of renal dysfunction on the basis of the level of an anti-inflammatory cytokine determined in step a).
Queen's University of Belfast and Belfast Health And Social Care Trust | Date: 2013-06-13
The present invention relates to a method for determining predisposition of a subject to developing renal dysfunction induced by physical trauma, hypotension, sepsis and/or septic shock syndrome, wherein the method comprises the steps of:a. determining the level of an anti-inflammatory cytokine present in a sample taken from the subject prior to physical trauma, prior to a hypotensive event, prior to sepsis, and/or prior to septic shock syndrome; b. determining if the subject is predisposed to developing renal dysfunction following physical trauma, hypotension, sepsis and/or septic shock syndrome on the basis of the level of an anti-inflammatory cytokine determined in step a).
Nugent B.,Belfast Health and Social Care Trust
Cochrane database of systematic reviews (Online) | Year: 2013
This is an update of a Cochrane review first published in The Cochrane Library in Issue 3, 2010.For many patients with head and neck cancer, oral nutrition will not provide adequate nourishment during treatment with radiotherapy or chemoradiotherapy due to the acute toxicity of treatment, obstruction caused by the tumour, or both. The optimal method of enteral feeding for this patient group has yet to be established. To compare the effectiveness of different enteral feeding methods used in the nutritional management of patients with head and neck cancer receiving radiotherapy or chemoradiotherapy using the clinical outcomes, nutritional status, quality of life and rates of complications. Our extensive search included the Cochrane ENT Group Trials Register, CENTRAL, PubMed, EMBASE, CINAHL, AMED and ISI Web of Science. The date of the most recent search was 13 February 2012. Randomised controlled trials comparing one method of enteral feeding with another, e.g. nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) feeding, for adult patients with a diagnosis of head and neck cancer receiving radiotherapy and/or chemoradiotherapy. Two authors independently assessed trial quality and extracted data using standardised forms. We contacted study authors for additional information. One randomised controlled trial met the criteria for inclusion in this review. No further studies were identified when we updated the searches in 2012.Patients diagnosed with head and neck cancer, being treated with chemoradiotherapy, were randomised to PEG or NG feeding. In total only 33 patients were eligible for analysis as the trial was terminated early due to poor accrual. A high degree of bias was identified in the study.Weight loss was greater for the NG group at six weeks post-treatment than for the PEG group (P = 0.001). At six months post-treatment, however, there was no significant difference in weight loss between the two groups. Anthropometric measurements recorded six weeks post-treatment demonstrated lower triceps skin fold thickness for the NG group compared to the PEG group (P = 0.03). No statistically significant difference was found between the two different enteral feeding techniques in relation to complication rates or patient satisfaction. The duration of PEG feeding was significantly longer than for the NG group (P = 0.0006). In addition, the study calculated the cost of PEG feeding to be 10 times greater than that of NG, though this was not found to be significant. There was no difference in the treatment received by the two groups. However, four PEG fed patients and two NG fed patients required unscheduled treatment breaks of a median of two and six days respectively.We identified no studies of enteral feeding involving any form of radiologically inserted gastrostomy (RIG) feeding or comparing prophylactic PEG versus PEG for inclusion in the review. There is not sufficient evidence to determine the optimal method of enteral feeding for patients with head and neck cancer receiving radiotherapy and/or chemoradiotherapy. Further trials of the two methods of enteral feeding, incorporating larger sample sizes, are required.
McCluggage W.G.,Belfast Health and Social Care Trust
Current Opinion in Oncology | Year: 2010
Purpose of review: Ovarian borderline tumours are relatively uncommon, but not rare, neoplasms. Pathologists and oncologists often struggle with various aspects of borderline tumours which are sometimes controversial and poorly understood. Recent findings: In this review, I discuss pathological and clinical aspects of ovarian borderline tumours of the two most common types, serous and mucinous, these having a different natural behaviour. The recent literature is reviewed as well as important papers prior to this. Controversial aspects covered include the relationship between borderline tumours and carcinomas, the significance of microinvasion, the significance of a micropapillary architecture in serous borderline tumours, the diagnostic criteria for and significance of extraovarian 'implants', lymph node involvement, staging issues and tumour behaviour. Summary: Ovarian borderline tumours have an excellent prognosis, although a small percentage is associated with the development of progressive disease. It has been suggested that the term borderline tumour should be abandoned but it is argued that this terminology should be retained for both serous and mucinous neoplasms because of the risk of extraovarian implants in serous borderline tumours and the large size and heterogeneity of mucinous borderline tumours which may result in an invasive focus being undetected by the pathologist. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Belfast Health And Social Care Trust | Date: 2013-05-20
The invention provides a LAMP assay for detection of meningococcal disease, the test comprising at least one nucleic acid primer set capable of detecting Neisseria meningitides in a LAMP based molecular test, the primer set being chosen from the primer sets listed in Table 1 as LAMP SETS 1 to 12 comprising SEQUENCE IDs from ID: 1 to ID: 69. Each assay consists of a primer set including of one pair of forward (HP) and reverse (BIP) inner primers, forward (F3) and reverse (B3) outer primers. The assay may also include loop forward (LF) and/or loop back (LB) primers to accelerate the reaction. Neisseria meningitides serotypes A, B, C, Y and W135 can be detected using the assay of the invention.
Agency: GTR | Branch: MRC | Program: | Phase: Intramural | Award Amount: 750.00K | Year: 2016
The genome is the complete set of genetic material in each of the cells of our body, inherited from our parents. Sometimes, changes (mutations) happen that cause disease. If someone has a disease, it’s now possible and affordable to read their genome to see if it might be caused by a mutation. If it has, scientists can use that information to understand the disease better, and perhaps one day treat or cure it. The UKs Department of Health (DH) set up its own company called Genomics England (GeL) to sequence the genomes of consenting families or individuals who suffer from rare genetic diseases and cancers. GeL has £100m from DH England to sequence 100,000 genomes. The MRC wants to work with the Devolved Governments of Northern Ireland, Scotland and Wales to help to develop in genome sequencing too, and to contribute to the 100,000 genomes project through GeL. We hope to help build a UK-wide partnership that can deliver better and faster results for patients. This £750,000 award is the MRC’s investment in the Northern Ireland Partnership, managed by the Northern Ireland Genomic Medicine Centre (NI GeMeC). It partners funding of £2.3m from the Northern Ireland Government. Together, funds will be used to sequence 1,300 genomes of people with rare diseases (and often also their families).