NIHRDataInsights/HRCSData huggingface dataset:
Title: Understanding how ‘lung cancer symptoms’ and ‘service’ factors drive the decision to seek help from a GP in the Scottish public: a discrete choice experiment
Funder: Cancer Research UK

Abstract: Background In the UK poor survival of lung cancer is largely due to late stage diagnosis. A significant contributor to late stage diagnosis is the patient delay in seeking help from a GP. Thus we know that people often find it difficult to decide when they should visit their GP. However, we do not know what combinations of symptoms and services are more likely to lead a person to consult a GP within a realistic and dynamic process of making choices. The discrete choice method has been successfully applied to public preferences for investigations in lung cancer. This study builds on the SYMPTOM study to help better understand why patients may choose not to visit the GP and suggest ways in which services could be improved to remove barriers to unmet need. This may provide an opportunity to shed compare decision-making in Scotland compares to the rest of the UK. Aims Principal research question: what combination of lung cancer ‘symptoms’ and general practice ‘service’ factors would more likely lead members of the public to seek help from their GP? We aim: • To understand why some people might not consult their GP, despite apparent clinical need and whether changing certain aspects of service provision might remove barriers to unmet need and facilitate consultation. Methods An electronic discrete choice questionnaire administered to 800 GP attenders in Scotland aged 40+ using an iPad. Participants will be presented with scenarios made up of six to ten factors: including symptoms and service factors outlined in NICE guidelines/literature reviews and qualitative data from the ongoing SYMPTOM study. Respondent’s hypothetical choices will be used to deduce the relative importance scores for each of the symptoms and service factors. Sub group analysis could enable us to understand whether socio-economic factors, health behaviours and co-morbidities are significantly associated with different decision-making profiles. For example, patients with COPD might be significantly less likely to consult for a persistent cough than those without. How the results of this research will be used This study has immediate policy relevance as it will assist in refining techniques (GP interventions or awareness campaigns) which encourage people to present with symptoms suggestive of cancer. Outputs of this research will help to design health services which are as accommodating and flexible as possible to encourage early presentation and thus lead to earlier diagnosis.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS
Title: The British Heart Foundation/Cancer Research UK Lynn MacFadyen PhD Studentship: 'E-cigarettes for harm reduction in people with mental illness'
Funder: Cancer Research UK

Abstract: Background:People with mental illnesses are more likely to be smokers than people without and consequently have a substantially lower life expectancy. While existing interventions for smokers with mental illnesses can be effective, this sub-population of smokers struggles with smoking cessation and would benefit from novel support mechanism such as harm reduction. Harm reduction is the attempt to reduce harm, psychological or physical, from smoking without complete cessation among those who are unable or unwilling to stop. Electronic cigarettes (e-cigarettes) offer one new way in which this can be achieved: e-cigarettes have been found to facilitate smoking reduction and may have higher acceptability than more conventional products for smoking reduction. However, it is currently unclear whether e-cigarettes confer any benefit in smokers with mental illnesses. Moreover, it is important to gauge the attitudes of health professionals engaging with these smokers in order to establish the feasibility of this approach, if proven effective.<br/>Aims:To investigate perceptions of e-cigarettes among both mental health professionals and individuals with mental illnesses and to evaluate the efficacy of e-cigarettes as a method for harm reduction in people with mental illnesses.<br/>Methods:Two sets of focus groups will be conducted with individuals with mental illness and mental health professionals to gather preliminary information about perceptions, acceptability of e-cigarettes and possible barriers to their use within this population. Qualitative results will inform the next stage of research, i.e. how both e-cigarettes and a trial might be made more acceptable to the target population given the barriers identified (e.g. address issues on information provision, cost, types of e-cigarettes used, specific trial design). At this stage, a two-arm randomised controlled pilot trial is proposed (intervention group=one month provision of e-cigarettes; control=best current treatment) to evaluate the efficacy of e-cigarettes for smoking reduction in people with stable mild/moderate mental illnesses. The primary outcome measure will be reduction in cigarettes smoked and expired air carbon-monoxide at 4-week follow-up.<br/>Application:The study will provide much-needed information on the potential contribution of e-cigarettes to harm reduction in individuals with mental illnesses. Results from the qualitative research provide insights into the perceived acceptability of this approach and will indicate whether implementation of e-cigarettes as a harm reduction measure is likely to be feasible in the particular context. The pilot trial will provide initial data on the efficacy of e-cigarettes for smoking reduction and effect estimates can be used to assess whether further, definitive trials are warranted.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS
Title: London Pancreas Workshop 2014
Funder: Cancer Research UK

Abstract: Background: Pancreatic cancer is a disease with dismal prognosis. The gains in improvement in survival over the last four decades have been marginal. The research conducted all over the world in presented in conferences and journals not dedicated to pancreatic cancer. Aim: To create a forum for state of the art clinical and basic research in pancreatic cancer. Methods: The London Pancreas Workshop was launched in 2006 and now convenes every two years. The Workshop attracts delegates from the UK and abroad, comprising of clinicians (surgeons, gastroenterologists, radiologists, pathologists, oncologists amongst others), scientists, pharmaceutical company representatives and pancreatic cancer charity representatives. A wide range of topics relating to pancreatic cancer clinical and scientific problems are discussed and progress updates presented. The focus remains on the cutting-edge research. How the results will be used: The forum serves as an excellent medium for education. It is also an excellent networking forum bringing scientists and clinicians together to collaborate in order to make difference in survival for pancreatic cancer patients. Further information is available on http://www.bci.qmul.ac.uk/seminars-a-events/london-pancreas-workshop.html.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: KHS101 down-regulates NOS2 expression and eradicates the stemness phenotype in glioblastoma
Funder: Cancer Research UK

Abstract: Background Within brain tumours niches exist where cancer cells adopt a stem cell like phenotype. These cells maintain the capacity to undergo self-renewal, give rise to differentiated progeny driving tumour growth and display resistance to conventional treatments. KHS101 is a synthetic compound that was identified from a phenotypic drug-screen. The drug-screen was devised to identify compounds capable of inducing neural stem cell differentiation. Within the Brain Tumour Stem Cell (BTSC) paradigm KHS101 mediated stemness dysregulation represents a viable therapeutic strategy to treat glioblastoma. Inducible nitric oxide synthase (NOS2) is a key regulator of stemness and BTSCs depend on NOS2 activity for tumourigenicity. KHS101 is selectively toxic to patient-derived glioblastoma cell lines and this toxicity is accompanied by down-regulation of NOS2 mRNA expression. This study focuses on providing further validation of NOS2 mRNA down-regulation as a marker of KHS101 activity in vitro and aims to extend our findings in an in vivo tumour xenograft model of glioblastoma. Furthermore we will conduct experiments to further extend our understanding regarding the mechanism behind KHS101 mediated NOS2 mRNA down-regulation. Aims To determine if the observation that KHS101 down-regulates NOS2 mRNA translates into a down-regulation of NOS2 protein levels in vitro. To determine if KHS101 induces NOS2 mRNA down-regulation in a glioblastoma xenograft model. To ascertain if KHS101 down-regulates NOS2 mRNA expression via disruption of Hypoxia Inducible Factor alpha (HIF-1a) binding to the NOS2 promoter. Methods Cell culture of multiple patient-derived glioblastoma cell lines. Western Blotting of cell line lysate to quantify NOS2 protein levels. RNA in situ hybridisation with probes against NOS2 and housekeeping genes on tumour xenograft tissue sections after in vivo exposure of tumours to KHS101. Chromatin Immunoprecipitation of cell line lysate using HIF-1a antibodies with subsequent PCR against genes of interests including NOS2. How the results of the research will be used Validating NOS2 as an in-vivo target of KHS101 would provide strong evidence to support NOS2 as a pharmacological response biomarker for KHS101 mediated activity against BTSCs.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: GeL-CRUK Cancer Pilot: Sample collection award
Funder: Cancer Research UK

Abstract: GeL-CRUK Cancer Pilot: to collect and genotype lung cancer tissue from patients with the aim of offering these patients participation in the national study, Matrix


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Preclinical evaluation of selumetinib and glucocorticoid combination therapy for the treatment of Ras pathway positive, high risk acute lymphoblastic leukaemia
Funder: Cancer Research UK

Abstract: Background Acute lymphoblastic leukaemia (ALL) is an aggressive malignancy of developing lymphocytes. Despite intensive multi-agent therapy, adults with newly diagnosed ALL and children with relapsed ALL have poor outcomes and novel therapies are clearly needed. Recently, we have identified mutations that activate the RAF/RAF/MEK/ERK pathway as a common genetic abnormality in ALL and shown an association with high risk disease. Importantly, we have demonstrated excellent activity of the MEK1/2 inhibitor, selumetinib, in specifically inducing apoptosis in Ras pathway positive ALL cells in vitro and in an orthotopic xenograft model, engrafted with primary ALL cells. In vitro data suggests significant synergy of selumetinib with glucocorticoids, pivotal agents in ALL, mediated by the propapoptotic Bim. Together, these drugs may offer clinical benefit for patients with Ras pathway positive ALL. Aims To assess the synergy and optimal scheduling of selumetinib and dexamethasone in Ras pathway mutated ALL cells in vitro and in an orthotopic model engrafted with primary ALL-derived cells. Methods In vitro cell viability assays with selumetinib and dexamethasone, alone and in combination will be performed in ALL cell lines and primagraft cells characterised for Ras pathway activation. Synergy will be evaluated by median effect analysis to determine Combination Indices (CI). Sequence dependence will be investigated and CIs compared. In vivo activity of single agent versus combination with optimal drug sequence will then be assessed in the orthotopic model engrafted with Ras pathway positive primagraft cells. To confirm proof of mechanism, pharmacodynamic evaluation will be performed by western blotting for p-ERK, Bim, cleaved caspase 3 and glucocorticoid induced leucine zipper. How the results of this research will be used. These data will be used determine the optimal design of phase II combination studies of dexamethasone and selumetinib for Ras pathway positive ALL and will define predictive biomarkers for patient selection.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: All Wales Molecular Genetics Laboratory Stratified Medicine Technical Hub: SMP2
Funder: Cancer Research UK

Abstract: In 2011, the CRUK Stratified Medicine Programme (SMP1) set out to work in collaboration with eight of the ECMCs, a network of 26 hospitals and three diagnostics labs, to tackle the challenges in delivering large scale, molecular testing in cancer within the NHS. In SMP1, by July 2013, over 9,000 patients had had their tumour samples tested for genetic defects that could be related to their cancer, proving that national screening of tumour biomarkers is not only feasible but also widely accepted by patients. Now, the programme is embarking on the next step, SMP2. In SMP2, we aim to set up processes and infrastructure in NHS hospitals and laboratories so that every patient in the UK with a specific type of lung cancer could have their tumour tested and potentially be given access to the best new drugs, to target specifically the defects in their tumour. To realise such an ambitious project, we have divided SMP2 in two operational areas: • Building on SMP1 to develop a collaborative national pre-screening network through the ECMC Network • Setting up and delivering a national clinical trial with a matrix structure (the National Lung Matrix Trial). The targets for the pre-screening are ambitious; we want to reach at least 2,000 non-small cell lung cancer patients per year. Using a new technology, their samples will be tested for a wide range of molecular defects and in a clinically relevant turnaround time, to enable the identification of patients eligible for the National Lung Matrix Trial. Running alongside this will be the collection of valuable patient data that will help future research into personalised medicines. http://www.ecmcnetwork.org.uk/news-events/news/Stratified_medicine_next_steps?view=rss


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: World Congress Cancer of Skin: meetings support
Funder: Cancer Research UK

Abstract: Background Skin Cancer is the commonest human cancer in the Western world. Latest estimates suggest that more than 260,000 skin cancers are seen each year in the UK and over a million in the US. Although treatment of early lesions is very effective by surgery and radiotherapy, there is high surgical morbidity as many patients develop multiple primary tumours. However there are still more than 2,000 skin cancer deaths in the UK with up to a third being from patients with non-melanoma skin cancer (particularly squamous cell carcinoma). There has been a lack of effective therapy for advanced skin cancer, but this has been transformed by the advent of targeted therapies. B-Raf inhibitors, MEK inhibitors and anti CLA4 reagents are in clinical trial for melanoma and drugs to inhibit Hedgehog signalling in basal cell carcinoma. Aims To support keynote speakers for the World Congress of Cancers Skin, 2nd -6th Sept 2014, Edinburgh International Conference Centre Methods The World Congress brings together researchers in both melanoma and non-melanoma skin cancer, and other rarer skin tumours in an international biennial meeting around the world. This is the first time that it has been held in the UK and it is being organised by a CR-UK programme grant holder as well as having multiple speakers from CR-UK. Support is being requested in this context. There are 4 tracks:Surgical; Molecular, Clinical and Mixed.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: CANCER AND NEOPLASMS
Title: Early Diagnosis Consortium Project - support for research assistant
Funder: Cancer Research UK

Abstract: The Early Diagnosis Consortium (EDC) is a major project between Cancer Research-UK, Cancer Research Technology, Abcodia Ltd and the Gynaecological Cancer Research Centre, UCL that was initiated in 2013. The project aim is to identify novel serum biomarkers for the early detection of lung, colorectal, oesophageal and pancreatic cancers by undertaking discovery and validation experiments in selected serum samples from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) biobank. The biomarkers discovery experiments will be outsourced to technology partners and will include technologies such as proteomics, autoantibody and microRNA analysis. The initial phase of the EDC identified which cancers would be studied and which technologies would be used and the project is now proceeding to Phase 1 to initiate the discovery experiments. The UKCTOCS biobank is curated by the Gynaecological Cancer Research Centre, UCL and is a serum samples collection from a unique prospective, population-based cohort of 202,000 post-menopausal women. The biobank contains significant numbers of samples collection before the diagnosis of a range of cancers which provide an ideal opportunity for the discovery of early detection biomarkers for cancers. The research assistant at the Gynaecological Cancer Research Centre, UCL will initiate, participate and assist in the acquisition and analysis of data from the UKCTOCS database in support of Early Diagnosis Consortium Project in order to identify cohorts of women with the specific cancers to be studied. There will also be a requirement for the postholder to supplement this data with additional data for these women from general practice and secondary care as required. The postholder will identify case samples together with matched controls required for the discovery experiments and liaise with the appropriate contacts at the Biorepository to arrange for sample retrieval, aliquoting and shipping to collaborator sites. Maintenance of documentation pertaining to the project is required by the post-holder as well as assisting with ethics application, annual reports to sponsors and funding bodies. Key working relationships are with the Members of the Gynaecological Cancer Research Centre, UCL , CRUK-CRT and the Abcodia team and staff at the off-site Biobank facility.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Newcastle ECMC, Stratified Medicine Programme 2, year 1
Funder: Cancer Research UK

Abstract: In 2011, the CRUK Stratified Medicine Programme (SMP1) set out to work in collaboration with eight of the ECMCs, a network of 26 hospitals and three diagnostics labs, to tackle the challenges in delivering large scale, molecular testing in cancer within the NHS. In SMP1, by July 2013, over 9,000 patients had had their tumour samples tested for genetic defects that could be related to their cancer, proving that national screening of tumour biomarkers is not only feasible but also widely accepted by patients. Now, the programme is embarking on the next step, SMP2. In SMP2, we aim to set up processes and infrastructure in NHS hospitals and laboratories so that every patient in the UK with a specific type of lung cancer could have their tumour tested and potentially be given access to the best new drugs, to target specifically the defects in their tumour. To realise such an ambitious project, we have divided SMP2 in two operational areas: • Building on SMP1 to develop a collaborative national pre-screening network through the ECMC Network • Setting up and delivering a national clinical trial with a matrix structure (the National Lung Matrix Trial).


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: European NF-kappaB subunit workshop
Funder: Cancer Research UK

Abstract: The NF-kappaB transcription factor plays a critical role in a number of cancer related processes such as proliferation, apoptosis, autophagy, immunity and metabolism. There are five subunits in the NF-kappaB family, each of which can have independent or combined functions in the regulation of these processes. However, although the NF-kappaB pathway is the subject of intensive research, the function of independent subunits is somewhat overlooked. Here we are applying for funding towards a workshop aimed at increasing our understanding of these subunits and their role in disease. A meeting such as this is unique in the field. The first European NF-kappaB subunit workshop was held in Germany in 2012 and was a tremendous success. The outcomes were increased collaboration, sharing of reagents/biological tools and more coherence in the community. With the 2014 meeting we aim to continue to build our knowledge in this subject area and increase relations across Europe. We also aim to increase speaker numbers and attendance, while maintaining the unique focus of the conference. All speakers at this conference pay their own way. However, to encourage participation we have kept these costs to a minimum. Therefore, we require additional funding so that the conference will break even. To this end, we are applying to CRUK for funding to sponsor the Cancer Biology session. This funding will contribute significantly to making this a very friendly, stimulating workshop that gives many junior scientists a chance to present their work and interact with PIs, and European PIs a chance to keep up to date with the research of colleagues in the NF-kappaB subunit field.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS