NIHRDataInsights/HRCSData huggingface dataset:
Title: Treatment for vulval intraepithelial neoplasia
Funder: Department of Health (England)

Abstract: Research Question: Which treatment is most clinically effective for the treatment of vulval intraepithelial neoplasia? 1.Intervention: Interventions for vulval intraepithelial neoplasia 2.Patient group: Adult women with vulval intraepithelial neoplasia 3.Setting: Any appropriate setting4.Control: 5.Study design: Evidence synthesis comprising an update of the Cochrane reviews on medical and surgical treatments for VIN and a network analysis to compare surgical and medical techniques in order to determine if there is a surgery versus drug treatment question.6.Important outcomes: Recommendations for future primary research Other outcomes: Response to treatment (resolution or regression) progression to vulval cancer QoL sexual functionNHS decision problem to be addressed by this research: Vulval intraepithelial neoplasia (VIN) is a precancerous condition of the vulval skin with a high risk of recurrence (>30%) and the progression to vulval cancer (2-9%). Prevalence is low but increasing particularly in younger women (35-55) where HPV infection is thought to be the cause.VIN may be treated surgically or with drug or photodynamic therapy. The main advantage of PDT and imiquimod (and similar drugs) is that if they work there is no alteration in the appearance of the vulva as opposed to the effects of surgery. Updates of the Cochrane reviews on medical and surgical treatments for VIN are required as well as a synthesis of these two reviews in order to identify the most clinically effective treatments and provide potential candidate treatments to compare in future primary research.Source of topic This topic came from an updated Cochrane review published in September 2011:Pepas L Kaushik S Bryant A Nordin A Dickinson HO. Medical interventions for high grade vulval intraepithelial neoplasia. Cochrane Database of Systematic Reviews 2011 Issue 4. Art. No.: CD007924. DOI: 10.1002/14651858.CD007924.pub2.End of search date September 2010.NICE and other guidanceNICE provides no guidance on the treatment of VIN.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: Understanding the gender differences in Barrett's Oesophagus and Oesophageal Adenocarcinoma
Funder: Tenovus Cancer Care

Abstract: Oesophageal Adenocarcinoma is one of the fasting growing cancers in the UK, with the incidence in Wales above the UK average. It is caused by longstanding acid reflux leading to a precursor condition called BarrettÃªs Oesophagus. Both BarrettÃªs Oesophagus and Oesophageal Cancer are more common in men than women, for reasons unknown. Detecting the pre-malignant BarrettÃªs Oesophagus condition and understanding the reasons some patients with acid reflux develop cancer is essential as the prognosis associated with this cancer is woeful. Our laboratory has already demonstrated that hormones can reduce the inflammation caused by reflux in cancer cells. We therefore aim to investigate the multitude of possible reasons behind this to better direct patients towards appropriate treatments. In short, the aim of this study is to identify the protective mechanisms that are associated with a female gender and why despite these some women still develop oesophageal cancer. This will direct future monitoring and treatment strategies. This study will assess the symptoms of heartburn, as well as dietary and lifestyle differences between genders through a detailed questionnaire and correlate this with blood hormone levels as well as a detailed analysis of the biopsy samples that are obtained from endoscopy. We anticipate the following outcomes: Identifying dietary and lifestyle differences between the genders which will become part of future patient education strategies. Identifying hormonal and molecular differences between genders, which will serve to be the basis for the development of better diagnostic methods to assess patientsÃª individual risk of progression to cancer as well as possible future therapeutic targets.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Open Wide: Can pre-emptive jaw exercises improve mouth opening and quality of life for head and neck cancer patients?
Funder: Tenovus Cancer Care

Abstract: Tumours in the mouth, back of the throat, base of tongue, salivary glands and the upper and lower jaw may require chemoradiation/radiation therapy to be delivered to the the jaw joints and muscles and therefore cause trismus. Trismus refers to damage and scarring of the jaw joints and muscles which can lead to a reduction in mouth opening. Trismus is defined as mouth opening less than 35mm. Significant trismus is defined as mouth opening below 20mm.Trismus can lead to poor oral hygiene, exposed bones, dental caries, difficulties in intubation and swallowing difficulties/reduced nutritional status as well as emotional distress regarding the functional impairment. This proposal is to seek funding for 0.2 wte Band 7 SLT who would be able to provide pre-emptive skilled therapeutic intervention to those patients who are due to have radiation treatment to tumours whereby treatment is likely to affect the jaw joints and muscles. The aim of the work would be to carry out a feasibility study to test the hypothesis that radiotherapy to the jaw joints and muscles causes trismus and that providing pre-emptive trismus exercises mitigates this reduction in mouth opening. The findings will be analysed and published nationally and the aim of this single centre small non-randomised study would be to assess the feasibility of a larger multi-centre randomised control trial.


Research activity codes: 6.7 PHYSICAL;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Lives at risk: Biographic, photographic and spoken accounts of what it means to be labelled at risk of breast cancer.
Funder: Tenovus Cancer Care

Abstract: This study engenders close collaboration between academics, surgical oncology clinicians and patient representatives to clarify what it means to be told you are â€¢at riskÃª of developing breast cancer. It concentrates on personal experience, management and care strategies, group comparisons, and impact on women and families. Two groups of women will be involved from: a) Cancer Genetics Department, Abertawe Bro Morgannwg Health Board (ABMU) because of family history but with no previous cancer episode; and b) Breast Care Unit, ABMU at risk of breast cancer recurrence.Phase 1: 24 women (12 each group, at low, moderate and high risk levels) will produce a â€¢book of experienceÃª showing and telling what it means to them. This may include photographs, drawings, writings, diary entries, and other material. At their discretion they may provide information about their care and family opinions, though the â€¢booksÃª must be theirs alone.Phase 2: Participants (12 each group, as above), will undertake semi-structured, qualitative interviews, consulting their â€¢booksÃª for support. Thematic analysis, alongside â€¢booksÃª analysed inter-textually, will illuminate experiences (hopes, fears, needs, expectations) and impact of risk status.Â¾Phase 3: Key Stakeholder Forum: stakeholders, study participants, patient/public representatives, researchers, clinicians and policy advisers underpinning wide-ranging dissemination.Â¾The study will achieve: heightened understanding of what it means to be told you are â€¢at riskÃª, group comparisons, recommendations for personal management, care and practice. Outcomes, aligned to existing research, knowledge and programmes (including history screening), will inform a report and dissemination plan leading to a larger, qualitative, multi-site study to include professional perspectives in other cancer groups and a wider UK demographic.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Thyroid autoimmunity (TPOAb) as a biomarker of outcome in women with breast cancer - large scale study from the TACT trial
Funder: Tenovus Cancer Care

Abstract: Immune reactions normally protect us against infections but occasionally the immune system also makes a reaction to a part of our own bodies _ referred to as an -autoimmune" reaction. The commonest autoimmune reaction is against the thyroid gland, and 12-18% of women over 40 have autoantibodies detectable in their blood directed against the enzyme that makes thyroid hormones _ thyroid peroxidase (TPO). Previous studies indicate that TPO antibodies are more common in women with breast cancer (up to 34% of women) and, importantly, that women with TPO antibodies have a better outcome from their cancer. However, the studies of the effects of TPO antibodies in breast cancer conducted so far have been small scale and the results remain controversial. In this application we propose to measure TPO antibodies in stored blood samples of 2000 women with breast cancer who took part in the TACT clinical trial around 10 years ago. This will allow us to determine the proportion with TPO antibodies and whether they were associated with cancer outcome over a long term period. If this large scale study confirms earlier findings it will identify a simple blood test (TPO antibodies) to indicate women likely to do better with breast cancer and perhaps need less aggressive treatment, and TPO could be used as part of a -breast cancer vaccine" to help the womenÃªs own immune system fight their cancer. The side effect of possibly causing an underactive thyroid would be easily treated with thyroid hormone tablets.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CANCER AND NEOPLASMS
Title: Perceptions and Attitudes of Cancer Survivors and Cancer Health Care Professionals in ABMU Health Board on the Welsh Government Cancer Key Worker Initiative
Funder: Tenovus Cancer Care

Abstract: The Cancer Key Worker concept was first introduced in the NICE Cancer Guidelines in 2004 stating that the cancer key worker is a coordinating role which is central to the patientÃªs cancer journey in providing information, support and guidance. In 2010, the Welsh Government (WG) National Standards for Rehabilitation of Adult Cancer Patients was published declaring by March 2011, every cancer patient in Wales should have a dedicated cancer key worker. In June, 2012, the WG Strategy, Together for Health- Cancer Delivery Plan for NHS in Wales again stated that Health Boards were to â€¢assign a Key Worker to each person with cancer, from the point of diagnosis onwards, to coordinate their ongoing careÃª. Unfortunately, implementation of the cancer key worker has been inconsistent across Wales. This is due to a lack of clear understanding of the role from Health Care Professionals (HCP) working in the cancer field and an erroneous definition. There is also deficiency in cancer patientÃªs perceptions of the key worker role and the potential benefits this role could bring to their cancer survivorship. This project aims to discover what different HCP disciplines (Doctors, Nurses, Physiotherapists, Occupational Therapists, Speech and Language Therapists) think of the cancer key worker concept. It aims to develop greater knowledge of the barriers to the implementation and highlight any differences amongst the professions all to improve execution. It will also discover perceptions and attitudes from different cancer patients on the role and the prospective benefits. This information will then provide us with more detail to implement the cancer key worker concept.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: Identification of mechanisms underpinning regulatory T cell involvement in disease.
Funder: Wellcome Trust

Abstract: The main function of our white cells is to eliminate infectious agents such as bacteria and viruses. These cells form part of the immune system and their activation is known as an immune response. Certain types of white cells, known as regulatory T cells, are believed to dampen down immune responses that are considered harmful these may be immune responses directed towards normal, uninfected tissues. As such the cells are thought to play an important role in preventing certain diseases known as autoimmune diseases e.g. multiple sclerosis and type I diabetes. Since tumours arise from normal tissues, regulatory T cells also inhibit immune responses to tumours. Thus, whilst the cells are useful for preventing autoimmune disease, they appear to impede the successful destruction of cancer cells. In light of these findings, the aim of this study is to find out how the actions of regulatory T cells can be harnessed for the purposes of treating disease. This is important since the discover y of mechanisms that promote their involvement in an immune response be identified will open up the possibility of inhibiting their activity in the case of cancer and promoting their activity for the treatment of autoimmune disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Inhibitors of Lysyl oxidase (LOX) for therapeutic use in metastatic cancer.
Funder: Wellcome Trust

Abstract: The spread of cancer through the body (a process called metastasis) is largely responsible for the death of cancer patients. Unfortunately, cancer is difficult to treat at this stage and in many cases the prognosis will be poor and the treatment options limited. Therefore, drugs that can prevent this process or that can be used treat cancer once in the advanced stage are greatly needed. We have shown that an enzyme called lysyl oxidase (LOX) is secreted into the circulation by cancer cells when the tumours get so big that their oxygen supply is no longer adequate (a condition called hypoxia). The LOX then contributes to the spread of the cancer cells by preparing a so-called site in a distant organ (essentually building a nest) to which the cancer cells can escape. LOX subsequently supports the growth of the cancer cells at this new site and so plays a critical role in the metastatic spread of cancer and ultimately in patient death. We propose to develop drugs that can block the role of LOX and thereby prevent the dissemination of cancer cells. These drugs should also block the growth of the cancer cells if they do get to the new sites, thereby inhibiting the spread of cancer through the body. Our aim is to produce drugs that are selective for LOX so that they have minimal side effects, but also to make sure that they can be taken orally to improve the quality of life of patients on this medication.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Characterisation and analyses of cancer genomes using next generation sequencing technologies.
Funder: Wellcome Trust

Abstract: Cancer is driven by genetic changes acquired throughout life. Identification of the recurrent mutations involved in each type of cancer is the first step towards the design of diagnostic and therapeutic strategies that specifically target the abnormal genes. In the last 1-2 years, DNA sequencing technologies have been developed that allow the identification of every genetic change in a given cancer sample, promising a new harvest of cancer genes. Firstly, I will develop the computational tools n ecessary to identify mutations within the vast arrays of data generated by these sequencing machines. Secondly, I will apply these tools to identify the spectrum of gene mutations found in 50 patients suffering from the commonest malignant blood disorder, the myelodysplastic syndromes. Thirdly, I will explore the use of new sequencing technologies for measuring disease burden in patients with breast and lung cancer. If successful, such approaches could be the first step towards developing treatm ent programmes that are individualised specifically for that patient s malignancy.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS
Title: Cellular responses to oncogenic Ras signalling.
Funder: Wellcome Trust

Abstract: Ras proto-oncogenes are key signalling intermediates sitting near the top of kinase cascades controlling cell proliferation, differentiation and survival. Three almost identical Ras isoforms are present in every cell however K-Ras is the isoform most commonly mutated in human cancers. Our study will define: 1. The relative abundance of Ras isoforms in cancer cells 2. The signaling network downstream of oncogenic K-Ras signalling 3. Cross-talk pathways that enable evasion of drug therapy targeted to RTK-Ras pathways Using paired isogenic cell lines harbouring mutant or wild type endogenous K-Ras we will use quantitative proteomics to measure changes to the phospho-protein signalling network downstream of active K-Ras. Follow-up work will use drugs targetting oncogenic nodes in the signalling cascade (eg. EGFR, B-Raf, PIK3CA, MEK) to investigate how cells compensate for drug treatment by rewiring their signalling. Meta-analysis of data from these proteomic experiments will generate K-Ras and drug response signatures. These will be fitted into interaction networks to identify pathways, principle components, hubs and bottlenecks coupled to K-Ras or compensatory changes. Predicted drug-resistance mediating genes will be followed-up in mutagenesis/RNAi signalling, imaging and phenotypic assays.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The histories of cancer policies and cancer care in the Netherlands and in England from c 1970, and their potential to inform policy debates.
Funder: Wellcome Trust

Abstract: The histories of cancer policy and cancer services in the Netherlands and in England will be explored for the period from 1970 to 2009, including palliative care, and using interviews as well as written sources. My preliminary research suggested that policies on cancer care in these countries show sufficient commonalities and differences to allow for insightful comparisons; by including the rather different dynamics of palliative services, I hope to gain further insights. I will use the secondary literature to set the two national histories in a wide international context. I will explore how cancer care was changed by different kinds of demands (political, professional and directly from patients) and how the systems compared in terms of effectiveness and responsiveness. The differences made by 'policy' have to be measured against estimates of the change that would have happened anyway, and for this purpose studies across time, and across countries may be particularly rewarding. I will develop my findings to show more generally how histories can inform health care policy. The thesis will contribute to the histories of health services and cancer care; it will aim to encourage historical evaluation of policy; it will try to show both how policy makers could have learned from history, and what they might learn from good history now.


Research activity codes: 7.2 END OF LIFE CARE;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: CANCER AND NEOPLASMS
Title: Chromatin regulation of self-renewal transcriptional programmes in leukaemia stem cells .
Funder: Wellcome Trust

Abstract: Stem cells are defined by their capacity for self-renewal and multipotent differentiation. Like normal tissues, many cancers including leukaemia have also been shown to contain cells with self-renewal capacity. Certain fusion genes that arise in the process of tumourigenesis can confer self-renewal properties to cells that have lost this ability, transforming them into leukaemic cancer stem cells (LSC). One such fusion gene is MOZ-TIF2. The protein produced by this fusion gene is an enzyme that alters the way DNA is packaged within the cell and may aberrantly increase/decrease the expression of genes that control self-renewal. MOZ-TIF2 also forms a complex with other proteins in the nucleus that help target the enzymatic activity of this protein. My project will aim to identify the genes controlled by MOZ-TIF2. I will also isolate the proteins that make up the MOZ-TIF2 complex and characterise how they help target the enzymatic activity of MOZ-TIF2. These insights will then be studied in mouse models of MOZ-TIF2 induced leukaemia to determine their role in the self-renewal of LSC. Finally, we will investigate the potential of novel drugs that inhibit the enzymatic activity of the MOZ-TIF2 complex as a potential therapy in the treatment of leukaemia.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The use of fragment-based drug discovery to identify novel drug candidates that modulate the BRCA2-RAD51 interaction for the treatment of cancer.
Funder: Wellcome Trust

Abstract: The proposed research is to develop an advanced lead compound for the treatment of lung cancer. We will use fragment-based methods to disrupt the protein-protein interaction between the human recombinase RAD51, and the hub protein BRCA2. This interaction is essential for DNA repair by homologous DNA recombination, a key cellular pathway involved in the resistance of cancer cells to ionizing radiation and radio-mimetic drugs. The target site is unique to RAD51 and binds FxxA tetrapeptide motifs in BRCA2. As part of a Wellcome Trust Translation Award we have used extensive X-ray structure determination to guide fragment-based approaches to develop several chemical series against this site. The project objectives are to increase the potency of our lead compounds and demonstrate in vivo potency. Lead compounds will be screened against a panel of normal and cancer cell-lines, particularly those derived from lung cancer, to establish their spectrum of anti-tumour activity, and to confirm their therapeutic window. The target and its mechanism will then be validated in xenograft assays. The overall objective is to significantly de-risk the target and the approach, and assemble a comprehensive package of chemistry, structural biology and early stage tumour biology for a potential licencee.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Mesenchymal Stromal Cells as Therapeutic Vectors for Metastatic Cancer.
Funder: Wellcome Trust

Abstract: Despite the major advances in cancer treatments over the past thirty years, once lung or other cancer types have spread, it is still incurable and all those affected die. The lungs are the commonest site of spread of cancer and lung failure the commonest cause of death. I have demonstrated that Mesenchymal Stem Cells (MSCs), cells found within bone marrow, preferentially travel to and infiltrate into tumours where they form some of the infrastructure called stroma. I have used MSCs to carry an a nti-tumour therapy to lung tumours by inserting a cancer cell killing gene called TRAIL (which does not harm normal cells) into these cells using a virus that I can switch on and off by treatment with an antibiotic. Using this system I have shown in initial experiments that I am able to control the growth of cancers and in almost 40% of cases eliminate them. This proposal examines how this therapy can be optimised for use in humans, ensuring that I deliver the best possible treatment to patients with few therapeutic options.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS