NIHRDataInsights/HRCSData huggingface dataset:
Title: TobaccoTactics.org. Monitoring tobacco industry activity to support health advocacy - developing a wiki as a new model of knowledge exchange.
Funder: Cancer Research UK

Abstract: BACKGROUND Article 5.3 of the Framework Convention on Tobacco Control requires signatories to protect their health policies ‘from commercial and other vested interests of the tobacco industry’. Guidelines operationalising this Article highlight the key role that civil society can play in monitoring the tobacco industry. To this effect, and funded by CRUK and Smoke Free Southwest, the Tobacco Control Research Group at the University of Bath has been developing a framework for monitoring and disseminating knowledge on the activities of the tobacco industry and their impacts on UK policy. In June 2012, the Group launched a ground-breaking new online resource – called TobaccoTactics.org. Utilising the same open software as Wikipedia, TobaccoTactics provides up-to-date information on the tobacco industry, its allies and others promoting a pro-tobacco agenda, exploring how the industry influences and distorts public health debates. At present there are nearly 500 TobaccoTactics pages with information that ranges from tobacco companies, their PR techniques to anonymous ‘tobacco trolls’. TobaccoTactics provides an innovative way of publishing contemporary research and has initiated the development of a new model of research dissemination in which preliminary findings are made publicly available online before being further analysed into traditional academic outputs. AIms The purpose of the present project is to establish the TobacoTactics wiki as a sustainable model of tobacco industry monitoring and knowledge exchange capable of responding to the rapidly evolving UK policy agenda. METHODS Using an established team of researchers and editors we will monitor and analyse the political, financial and marketing activities of the tobacco industry in the UK through a variety of means including the mainstream media, trade and industry publications, and the activities of those promoting pro-tobacco opinions via the internet and social media. A key focus will be on debates around generic packaging including how the industry in the UK is revisiting many of the misleading strategies employed in attempts to derail legislation in Australia. HOW THE RESEARCH WILL BE USED While the findings will be used for further academic outputs from the Tobacco Control Research Group at Bath, it is also anticipated that the wiki will be widely used by a growing network of academics, health advocates, journalists, civil servants and politicians to stay informed about pressing issues in tobacco control, identify trusted story lines and examine the credentials and affiliations of apparently independent voices featuring in public health debates.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: CANCER AND NEOPLASMS
Title: Manipulating the quiescent cancer stem cell niche in colorectal cancer
Funder: Cancer Research UK

Abstract: Background Whilst significant improvements have been made over the last few decades in the treatment of colorectal cancer large numbers of patients still succumb to the disease. Although many chemotherapies appear highly effective in laboratory experiments this often fails to translate into the same effect on tumours given as neo-adjuvant and adjuvant treatments. One of several hypotheses explaining this resistance of some tumours to chemotherapies relates to the presence of cancer stem cells that, while driving tumour growth and metastasis, are also inherently highly resistant to chemotherapy. Emerging data from the field suggests that this cancer stemness is not 'hard wired' and that tumour cells can gain and lose the cancer stem cell phenotype in response to external niche signalling cues from adjacent cells and the stromal microenvironment. Recently generated data further suggests that most intestinal cancer stem cells are paradoxically quiescent. Aims This project aims to explore the response of quiescent and cycling colorectal cancer stem cells to alterations in niche signalling pathways known to govern the behaviour of stem cells previously identified in the normal intestinal epithelium. The hypothesis of the project is that manipulation of these pathways will cause alterations in cancer stem cell behaviour that will generate increased susceptibility to chemotherapies currently in use without causing deleterious effects on the normal intestine. Methods The project will explore the response of colorectal cancer stem cells to niche manipulation using a combination of in vitro 2D and 3D cell culture techniques and in vivo validation using modern lineage tracing techniques in murine intestinal cancer models together with xenotransplantation of primary human colorectal carcinomas. In vivo manipulation of signalling pathways will be performed using direct administration of signalling ligands as well as adenoviral mediated hepatic transfection in combination with the traditional cytotoxic 5-Fluorouracil. How the results of this research will be used The results from this project may lead to direct benefit for patients with colorectal cancer by improving the efficacy of current chemotherapies without increasing the side effect profile that would come from the addition of further cytotoxics. Should the project show benefit in colorectal cancer then it may pave the way for similar approaches in other cancers.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Cancer Epidemiology Unit, University of Oxford
Funder: Cancer Research UK

Abstract: Background Over the last decade we have established some of the largest epidemiological studies in the world to investigate avoidable causes of cancer. Aims Our research aims to identify potentially modifiable causes of cancer. Methods Detailed prospective information on lifestyle and behavioural factors, including diet, smoking, alcohol, body size at various ages, physical activity, and hormonal and reproductive factors, is available in our large cohort studies, the Million Women Study and EPIC-Oxford. Around 99% of cohort participants are still being routinely followed for cancer registrations and mortality, with 150,000 incident cancers already accrued and 200,000 expected by 2018. The recent establishment of a national Cancer Outcomes and Services Dataset means that detailed pathological and clinical site-specific information is now routinely available, including tumour stage, grade, histology, laterality, molecular markers, and treatments. Electronic linkage of the Cancer Outcomes and other NHS datasets to our cohort data will substantially enhance the range of questions we can address in the next 5 years. In particular, we will have sufficiently detailed pathological and clinical information on large enough numbers for many cancer sites to assess reliably whether specific tumour subtypes are heterogeneous in their causation. For questions of major public health importance, bringing together and reanalysing the worldwide published and unpublished evidence avoids undue emphasis on just what has been published. The international collaborations that we host will continue to provide new information on potentially modifiable causes of breast, prostate, ovarian and endometrial cancer. Hundreds of collaborators are involved, and findings from these collaborations have been highly influential. A new collaboration is planned, combining international data on cancer incidence in vegetarians. Collaboration with the NHS Cancer Screening Programmes is expanding. Working with the NHS Breast Screening Programme, we serve as the co-ordinating centre for the largest ever randomized trial, randomizing 3 million women to assess the direct and indirect effects of offering additional breast cancer screening before age 50 and after age 70. Combining data from the recently established NHS Bowel Cancer Screening Programme with our prospectively collected cohort exposure data will strengthen research on the aetiology of colorectal cancer, a common but poorly understood malignancy. How results will be used Our research has yielded, and will continue to yield, important results that inform policy makers, health practitioners and the general population about what can be done to reduce cancer incidence.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Dundee Cancer Research UK Centre - Bridging Funding (Core)
Funder: Cancer Research UK

Abstract: The Dundee Cancer Research UK Centre brings together scientists, doctors and nurses from Dundee and Tayside. Collaboration is the key to the success of the Centre, ensuring that cutting-edge research brings benefits to patients in and around the city. The Centre is a partners between Cancer Research UK, the University of Dundee and NHS Tayside. Researchers at the Dundee Centre will focus on skin, breast and bowel cancers. They will also build on their world-class research into cancer surgery to develop more effective ways of using this cornerstone treatment. Scientists in Dundee are internationally recognised for their work into cell biology û studying the key processes that take place in healthy cells and how these go wrong in cancer. They are also investigating genetic faults that increase the risk of cancers such as bowel cancer, and finding out how some genes can influence a patientÆs response to treatments. A key aim of the Dundee Centre is to encourage the expansion of translational research in the city û using scientists' discoveries in the lab to design new ways to diagnose and treat cancer. For example, researchers investigating melanoma skin cancers are exploring why some patients become resistant to treatment, aiming to combat this problem and save more lives. Another strength in Dundee is clinical research using imaging to improve surgical techniques for several types of cancer. Through clinical trials, these innovative new treatments are being offered to patients in Dundee and Tayside. Staff at the Dundee Centre will also improve training for cancer nurses as well as working with local people to raise awareness of disease symptoms and ways to reduce their risk. Grants support a variety of training projects - where available coding is done on the basis of these individual pieces of research.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Dundee Cancer Research UK Centre - Senior Research Nurse (Bridging Funding)
Funder: Cancer Research UK

Abstract: Senior research nurse associated with: The Dundee Cancer Research UK Centre brings together scientists, doctors and nurses from Dundee and Tayside. Collaboration is the key to the success of the Centre, ensuring that cutting-edge research brings benefits to patients in and around the city. The Centre is a partners between Cancer Research UK, the University of Dundee and NHS Tayside. Researchers at the Dundee Centre will focus on skin, breast and bowel cancers. They will also build on their world-class research into cancer surgery to develop more effective ways of using this cornerstone treatment. Scientists in Dundee are internationally recognised for their work into cell biology û studying the key processes that take place in healthy cells and how these go wrong in cancer. They are also investigating genetic faults that increase the risk of cancers such as bowel cancer, and finding out how some genes can influence a patientÆs response to treatments. A key aim of the Dundee Centre is to encourage the expansion of translational research in the city û using scientists' discoveries in the lab to design new ways to diagnose and treat cancer. For example, researchers investigating melanoma skin cancers are exploring why some patients become resistant to treatment, aiming to combat this problem and save more lives. Another strength in Dundee is clinical research using imaging to improve surgical techniques for several types of cancer. Through clinical trials, these innovative new treatments are being offered to patients in Dundee and Tayside. Staff at the Dundee Centre will also improve training for cancer nurses as well as working with local people to raise awareness of disease symptoms and ways to reduce their risk.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Liverpool Cancer Research UK Centre - Bridging Funding (Core)
Funder: Cancer Research UK

Abstract: The Liverpool Cancer Research UK Centre sets the pace for national and international progress in pancreatic, head and neck, and blood cancers. It will also concentrate on pioneering the latest techniques in surgery, radiotherapy and the treatment of children's cancers. Collaboration is the key to the success of this virtual Centre, a partnership between the Royal Liverpool University Hospital, Clatterbridge Centre of Oncology NHS Trust, the University of Liverpool, the Liverpool City Council, the Merseyside and Cheshire Cancer Task Force, and Cancer Research UK. It aims to be a world leader in developing treatments tailored to individual cancer patients based on understanding the biology of the disease and how that varies among patients. Researchers will also be focusing on a better understanding of how cancers start and behave, developing more effective treatments with fewer side effects, and tackling cancer in low-income communities where survival is lowest.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: GTPase Signalling in Cancer
Funder: Cancer Research UK

Abstract: Background: Metastasis is a major clinical problem in cancer. We aim to understand molecular mechanisms underlying metastasis through study how cell signalling regulates tumour cell migration and invasion. We study the Rho and Ras subfamilies of small GTPases because of their key roles in controlling cell behaviour such as migration. A major focus is the regulation of GTPase activity through Guanine Nucleotide Exchange factors (GEFs) and GTPase Activating Proteins (GAPs), as these generate specificity in signalling and may be more tractable drug targets than the GTPases. To investigate signalling we employ in vivo approaches and tissue culture utilising RNAi screens, proteomics and assays for cell migration. To generate genetic systems for in vivo work we have made conditional alleles of Rock1 and Rock2, key effectors of Rho signalling and Rala and Ralb, which act downstream of oncogenic Ras. Using these approaches we have shown that ROCK has a key role in cell proliferation, revealed a novel role for RAL signalling in mitosis and provided strong genetic evidence for a specific role of RALB in metastasis. Aims: • Identify GEFs and GAPs regulating Rho family GTPase activity in melanoma and investigate how they contribute to modes of cell migration and the malignant phenotype. • Understand the role of the tumour suppressor PTEN in different modes of melanoma cell migration. • Understand the roles of Rho signalling in cancer by investigating ROCK1 and ROCK2 and a novel effector family FAM65. • Exploit our conditional knockouts of Rala and RalB to gain mechanistic insight into the roles of RAL proteins in invasion and metastasis How will the results be used? We will contribute to the understanding of the molecular basis of cancer by delineating mechanisms of cancer cell migration, invasion and metastasis. We hope to identify and validate therapeutic targets. Blocking cell migration and invasion could be effective in clinical situations such as preventing surgery enhanced metastasis, avoiding dissemination of tumour cells during cytostatic therapies and blocking re-seeding of the primary tumour from metastases.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Cancer mortality and incidence in the British Rubber industry – a 45 year follow-up
Funder: Cancer Research UK

Abstract: Working in the industry that has manufactured rubber and rubber products has been determined to be carcinogenic. However, given the complex nature of the chemicals present or in use, the phasing out of the use of certain chemicals, and the trend in reduction in exposures, there remains a great deal of uncertainty about the nature of the risks, if any, encountered by workers in industry today. We have at our disposal a large retrospective cohort study of over 40,000 workers who were aged 35 or over in 1967 and which was last followed up to 1976. This is the largest and statistically most powerful cohort of its type anywhere in the world. We propose to carry out an updated analysis of the cancer mortality in this cohort to determine which cancers are in excess, the extent to which they are in excess and, via a detailed occupational exposure assessment, determine the nature of the dose-response relationships for the most important known and suspected carcinogens. Furthermore, the work will complement an ongoing pooling of European rubber workers’ cohorts coordinated by the International Agency for Research on Cancer (IARC) but in which, despite its importance, the UK is not included. This analysis will add substantially to our knowledge of the risks associated with the chemicals present in the industry in the UK and importantly also the developing world. It has the very real potential to fill an important gap in scientific knowledge identified by IARC to influence policy and work practices as a result of better risk assessments in the industry throughout the world both now and in the future.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Impact of therapy on pre-leukaemic clones in Acute Myeloid Leukaemia
Funder: Cancer Research UK

Abstract: Background: Acute myeloid leukaemia (AML) is the most common aggressive adult leukaemia affecting approximately 2200 new patients a year in the UK alone. The incidence of AML increases with age; 80% of cases affect patients over the age of 60. In this age group, median survival averages 3 months, with only a 5% cure rate. In younger patients under the age of 60, the rate of cure for these patients remains at best ~45%. The major cause of mortality in both age groups is disease relapse. Importantly, few new curative treatments have been developed for AML in the last 3 decades[1]. AML is a genetically heterogeneous clonal malignancy of bone marrow stem/progenitor cells. There are many different pathogenic cytogenetic rearrangements (e.g. translocations) and sequencing of AML genomes has demonstrated that there are ~4-10 driver mutations per patient and 2-8 subclones at diagnosis and relapse[2,3]. Many of the genetic changes are prognostic and now direct risk stratified treatment pathways[1,4]. Aims I will undertake a 9 month project as part of my Academic Clinical Fellowship to prepare me for a Clinical Training Fellowship Application (end of 2013). The aim is to join an established project that will: (i) introduce me to AML biology; (ii) allow me to learn key techniques (e.g. flow cytometry, PCR based targeted re-sequencing); (iii) participate in a publication. I will work closely with a Vyas laboratory post-doctoral fellow (dr Quek) to determine: i. What is the impact of combination chemotherapy on pre-leukaemic HSC? Do pre-leukaemic HSC persist after combination chemotherapy? ii. Are pre-leukaemic HSC related genetically to the major clone at relapse? How will the results of this research be used? We will understand if the pre-leukaemic HSC population has to be eradicated to prevent AML relapse and cure AML. Moreover, the work will hopefully lead to a publication. References: 1. Burnett, A., et al. Therapeutic advances in acute myeloid leukemia. J Clin Oncol, 2011. 29(5): p. 487-94. 2. Welch, J.S., et al. The origin and evolution of mutations in acute myeloid leukemia. Cell, 2012. 150(2): p. 264-78. 3. Ding, L., et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature, 2012. 481(7382): p. 506-10. 4. Patel, J.P., et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med, 2012. 366(12): p. 1079-89.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: The role of the Bone Morphogenetic Protein (BMP) pathway in the pathogenesis of inherited and sporadic colorectal cancers
Funder: Cancer Research UK

Abstract: Backgound. Colorectal cancer affects more than 39,000 people/year in the UK and the majority of these tumours develop from pre-malignant precursors - colorectal adenomas and serrated polyps. Dysregulation of the morphogen signalling pathways that control the intestinal stem-cell can lead to tumour initiation and abnormal morphogen expression can be detected in early colorectal polyps. Using genetic and functional studies of familial and sporadic colorectal neoplasia we have shown the involvement of constituents of the Bone Morphogenetic Protein (BMP) pathway in colorectal cancer initiation and progression. Aims 1. To determine whether BMP constituents initiate tumourigenesis by the induction and/or maintainence of stem-cell properties. 2. To examine the expression of BMP constituents in early and late human colorectal tumours and investigate their contribution to tumourigenesis. 3. To investigate how the BMP and Wnt pathways interact and how this affects the classical (APC initiated) intestinal tumourigenesis pathway. 4. To determine whether BMP dysregulation is mechanistically involved in mediating and/or subverting oncogene induced senescence particularly in the initiation of the serrated carcinogenesis pathway. Methods. Hypotheses are developed on the basis of observations made in human endoscopic or surgical surplus tissue. Functional model systems are then generated to test these hypotheses. Cell-line models will investigate stem-cell properties using intestinal organoid culture systems Gain-or-loss of function experiments in primary and cancer cell-lines will be used to mimic or reverse the changes seen in human lesions. Research outcomes. Understanding how inherited risk predisposes towards polyp generation can lead to important mechanistic insight into intestinal tumourigenesis. Having helped to establish a causative role for BMP pathway disruption in colorectal carcinogenesis I would now like to investigate the functional mechanisms that underly this role. Understanding how, why and which polyps develop into cancers could lead to the development of colorectal tumour biomarkers that could greatly increase the effectiveness of bowel cancer screening programs Mechanistic insight into tumour initiation may also inform the search for new 'druggable' targets as the therapeutic manipulation of disrupted morphogens in the colorectum remains a tantalising prospect.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS