NIHRDataInsights/HRCSData huggingface dataset:
Title: Micro-IGES - Microscopic Image Guided Endoluminal Surgery.
Funder: Department of Health (England)

Abstract: The current surgical technique for removing cancer from the body is generally effective however it carries a significant risk to patients during surgery and long-term post-operative problems such as chronic pain, disfigurement and poor quality of life. Early stage cancer within a lumen, such as the colon, and precancerous polyps, can be removed endoscopically, thus avoiding the need to make a large incision on the body and potentially the creation of an artificial opening from the colon through the abdominal wall (colostomy). However, with the current instrumentation design, even tumours close to the external orifices of the bowel are difficult to remove with absolute certainty of completion. Micro-IGES provides a novel microscopic surgical platform with a greater degree of precision and accuracy through integrated sensing, probe-based microscopic imaging and robotically assisted intra-operative guidance. The platform will be evaluated in both in-vivo animal models and human clinical studies. The major healthcare impact includes an enhanced care-pathway for one-stop diagnosis and treatment, as well as improved post-surgical quality of life, particularly to the aged and those who cannot withstand major procedures, which represent a significant healthcare burden to the NHS.


Research activity codes: 6.4 SURGERY;5.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: SmartTarget: Image-guided Diagnosis and Treatment of Localised Prostate Cancer.
Funder: Department of Health (England)

Abstract: a) Rather surprisingly, early prostate cancer is managed without knowing where the cancer is within the prostate. This leads to some important cancers being missed and many unimportant cancers being detected. To compensate, all treatments are directed to the prostate not the cancer. This results in the side-effects that are so familiar urine leak, sexual problems, rectal symptoms We believe that by simply providing the clinician with information on the cancer location we will transform prostate cancer care. Imaging, in the form of MRI, can detect the prostate cancers that are harmful. The challenge lies in getting the information from the MRI to the doctors doing the biopsies and the treatments. b) We believe that our technology SmartTarget can do this. It will allow the cancer to be seen' on the ultrasound in the way a fighter pilot is presented with a target on a head-up display. c) Our goals are to: i) Develop a prototype SmartTarget device ii) Test the device in simulation studies and clinical trials iii)Develop detailed plans to roll out SmartTarget within the NHS d) The Result: i) fewer and better biopsies, ii) fewer and better treatments that cause less harm and carry less cost.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: Smart laparoscopic liver resection : Integrated image guidance and tissue discrimination.
Funder: Department of Health (England)

Abstract: Liver cancers can be removed using key-hole liver surgery which is less painful than traditional open surgery. However few cancers are removed by this method because of the difficulty in identifying and dividing blood vessels within the liver using key-hole surgery techniques. In addition, the positions of the tumour and major vessels in the liver alter during the surgery. We propose to use the CT scan taken prior to surgery to identify the location of the cancer and hence build a computer model of the liver for the surgeon which mimics the changes that take place during surgery. We will use this to track the position of the cancer and the major structures to the liver during the course of the key-hole surgery. This will be combined with a new method of detecting what kind of tissue is directly in front of the cutting instrument. This system is likely to result in a significant increase in the proportion of patients who may benefit from key-hole liver resection. The system will be validated on pigs and then evaluated on at least 25 patients. The system developed will also be applicable to operations on the pancreas, kidney and gallbladder.


Research activity codes: 6.4 SURGERY;5.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: CRUK/09/012: HYMN: A randomised controlled trial comparing hyperthermia plus mitomycin to a second course of bacillus Calmette-Guérin in patients with recurrence of non-muscle invasive bladder cancer following BCG induction.
Funder: Cancer Research UK

Abstract: The study will determine the efficacy of hyperthermia and mitomycin (HM) in patients with recurrence of high-grade non-muscle invasive bladder cancer (NMIBC) following induction BCG and who are not suitable for radical cystectomy. This group of patients are at significant risk of recurrence and progression to muscle invasive disease. Despite a response rate of up to 30% following a second course of BCG, there is no accepted standard second line therapy. Hyperthermia is a novel technology delivering intravesical mitomycin at temperatures between 42-45oC to improve drug uptake, increase drug reaction rate and inhibit DNA repair. Phase II trials have reported favourable results for HM compared to MMC mono-therapy in patients with high risk NMIBC and early phase studies indicate that HM is effective in patients with refractory disease following BCG induction. This trial will randomise patients to HM versus a second course of BCG. The primary outcome is disease free recurrence at 12 and 24 months, secondary outcomes include progression to invasive disease and complete response for patients with cis. The study includes quality of life, health economic and translational components and addresses an unmet need for a treatment that is effective with acceptable side effects, in disease relapse after initial BCG therapy.


Research activity codes: 6.3 MEDICAL DEVICES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Molecular pathology of colorectal cancer: Role of microRNAs in colorectal cancer pathogenesis and progression
Funder: Cancer Research UK

Abstract: Background Metastases are the principal cause of death in colorectal cancer (CRC), however the mechanisms influencing metastasis in CRC remain unclear. MicroRNAs (miRNAs) are powerful regulators of gene expression strongly implicated in initiation and progression of cancer, however little is known about their role in CRC. This project aims to identify miRNAs of importance in CRC progression. Methods I am analysing miRNA expression profiles in validated cell models of CRC progression alongside tumours of different stage. RNA samples are analysed with miRNA microarrays containing over 650 probes. An outstanding tissue series of human CRC with 5-year follow up data in conjunction with CRC liver and lung metastases is available. Normal mucosa will be compared with matched Stage I/II and Stage IV tumours; and stage II tumours with and without recurrence will be compared. Laser Capture Microdissection (LCM) will be used for tumours to reduce stromal and immune cell contributions. Array results are validated by qRT-PCR. Targets of candidate miRNAs are identified bioinformatically and tested experimentally. Biological consequences of interactions will be tested by overexpression or knockdown of miRNAs and assessed by standard in vitro assays. Results 112 miRNAs are overexpressed and 37 underexpressed in cell models of CRC progression. High scoring candidates have been verified by qRT-PCR in vitro and in LCM of tumour specimens. Targets of candidate miRNAs have been identified bioinformatically and are being evaluated experimentally. Applications MiRNAs differentially expressed in metastatic and non-metastatic cancers may help improve staging, guide therapy, and represent novel therapeutic targets.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Award title unavailable in public dataset
Funder: Wellcome Trust

Abstract: Adhesive interactions between cells and their surrounding extracellular matrices (ECM) control diverse processes such as cell survival, migration, and tissue assembly. In addition, dysfunctional ECM and cell-ECM interactions contribute to many human diseases, including arthritis, atherosclerosis and cancer. The Wellcome Trust Centre for Cell-Matrix Research (WTCCMR) is a multidisciplinary research centre embedded within the Faculty of Life Sciences at the University of Manchester. The long-te rm aims of the WTCCMR are to elucidate the structure and function of ECM and their cellular receptors, to define the role of ECM and cell-ECM interactions in normal development and human diseases, and to develop approaches for preventing and treating such diseases. The strategy employed to address these aims has been to recruit a team of researchers with overlapping interests and complementary skills, and to facilitate their work by providing a physical and technological environment of the high est standard. The research plan outlined in this proposal has been crafted to advance our understanding of the basic mechanisms of ECM function, and to suggest experimental strategies for correcting ECM defects and repairing dysfunctional tissues. The application seeks to renew Centre status and requests funds to support the core infrastructure of the WTCCMR.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Novel biomarkers to improve outcomes for breast cancer patients at risk of bone metastases: a proteomics-based approach
Funder: Cancer Research UK

Abstract: Background Despite major advances in treatment, around 12,000 UK women die of advanced breast cancer annually, with over 70% developing bone metastases and their devastating effects. Research on the biology of bone metastases is leading to new targeted therapeutic options, with ongoing, large, randomised adjuvant trials, which may delay or even prevent bone metastases. Relevance to cancer There is a clear need for biomarkers that predict patients at high risk of developing bone metastases, so that therapies can be selected on a more rational basis. Specific aims of the research To discover, validate and develop one or more biomarkers for predicting the development of bone metastases in individual breast cancer patients. Outline plan of research The work will harness the combined expertise of Leeds and Sheffield in state-of-the-art proteomics, bone biology and bone oncology and the very large patient base of both centres (5m population) in a dual approach: • membrane proteomic techniques will be employed to discover proteins associated with a ‘homing’ to bone phenotype of MDA-MB-231 breast cancer cell lines, with the aim of then searching for such candidate proteins in the patient samples • Using our unique access to prospective blood samples from patients in the AZURE trial (taken before development of bone metastases) and serial samples collected before, during and after development of bone metastases, a range of proteomic techniques, including selective targeting of calcium binding proteins, will be used to identify and validate proteins which can be developed into biomarkers which predict bone metastasis development.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Senior Clinical Research Fellowship: Analysis of the IRF4 gene regulatory network in B-cell malignancies: linking disease mechanism and biomarker detection
Funder: Cancer Research UK

Abstract: The goal is to understand how the behaviour of lymphoma and myeloma is controlled by dissecting a network of factors which regulate genes in these common cancers. This information will be used to identify markers which allow better tumour classification for improved patient care.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: The genetic epidemiology of cancer
Funder: Cancer Research UK

Abstract: To identify gene variants that are common in the population and i) influence susceptibility to ovarian cancer ii) are associated with the pathological features of breast and ovarian cancer, and iii) affect the clinical characteristics of breast and ovarian cancer.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: CRUKD/10/028 A Cancer Research UK Phase I trial of MK0752, an oral notch inhibitor, alone or in combination with gemcitabine in locally advanced or metastatic pancreatic cancer
Funder: Cancer Research UK

Abstract: This is a Cancer Research UK Phase I/IIa Trial of an Oral Notch Inhibitor (MK-0752) in combination with gemcitabine in patients with advanced (stage IV) pancreatic cancer. It is an open label, multi centre, nonrandomised Bayesian Adaptive Phase I/IIa study. Approximately 60 patients with Stage IV pancreatic cancer will be entered into this study, which will have a duration of around 24 months. It is expected that approximately two patients will be recruited each month. Phase I, the initial dose escalation phase, will take place to identify the recommended Phase II dose. In this phase, MK-0752 will be administered orally on Days 1, 8, 15 and 22 of a 28 day cycle. There will be an initial two weeks at the start of each patient’s treatment where they receive MK-0752 alone (Day 14 and Day 7, Cycle 1 only). The starting dose will be 1200 mg. Gemcitabine will be given intravenously on Days 1, 8 and 15 of a 28 day cycle as a 800 mg/m2 or 1000 mg/m2 dose. Two patients will be treated at each dose level. Once two patients have completed the first cycle of treatment (Day 28), data will be incorporated into a computer program used by the Lancaster University to determine what the next level of drug administration will be. The decision to dose escalate and number of patients to be treated at any given dose level (beyond two patients) will be made by the DDO and the Investigators after review of all available toxicity data and output from the Lancaster University program. Approximately 27 patients will be treated at the MTD as determined from the Bayesian adaptive model. Patient recruitment will continue until approximately 27 patients are evaluable for response at 12 weeks. (http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=8449).


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Class IA PI 3-kinase isoforms in oncogenic signalling
Funder: Cancer Research UK

Abstract: PI 3-kinases (PI3Ks), a family of molecules which transmit signals inside cells, are deregulated in cancer. We aim to determine the roles of the individual PI3K family members in cancer, using genetic murine models. This will help the ongoing development of medicines to block PI3K activity.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Probing and targeting hypoxic response networks in tumorigenesis with small molecules: towards the next generation of healthcare
Funder: Cancer Research UK

Abstract: Protein-protein interactions are the central component of most biological processes, playing a critical role in cellular response to disease. The potential of specifically modulating such interactions with small molecules promises to replace current symptom-driven approach to diagnosis and treatment, and to dramatically alter the approach to healthcare. Our research endeavors lie at the interface of the physical and biological sciences, using the tools of molecular biology, synthetic chemistry and nanotechnology to detect, target and modulate specific protein-protein interactions. We have a strong track record in this field, with several high-profile publications and ongoing collaborations in the UK, Europe and USA. Here, we outline a multi-disciplinary approach to the discovery, characterisation and utilisation of small molecule inhibitors of protein-protein interactions that play a key role in the development, growth and spread of tumours. We will use our methodology to target angiogenesis, by uncovering small molecules that selectively inhibit HIF-1 or HIF-2 dimerisation, using the uncovered molecules to better understand the role of these proteins. We will use these compound to investigating and better understand the opposing roles of HIF-1a and HIF-2a in the deregulation of oncogenes via the MYC-MAX transcriptional pathway. The uncovered specific inhibitors of HIF-2 dimerisation will be also used to develop compounds that target carcinoma in von Hippel-Lindau disease. We will develop a fluorescence based reverse two-hybrid system, allowing the automation of the genetic selection process with a cell sorter. We will use this automated genetic selection system to better characterize the role of the Id (inhibitor of differentiation/DNA binding) protein family in tumourigenesis. Up-regulation Id-1 has been shown to confer resistance to taxol and other chemotherapeutic drugs in a variety of cell lines, and Id-1 expression also correlates with cancer progression and metastasis in several cancer types including prostate, cervical, ovarian and breast. We will also construct a nano-sensor, capable of selectively binding a targeted protein. This will allow monitoring and identification of the target protein in biological samples. This technology has the potential to allow early detection of cancer, based on identification of the protein markers. Targeting processes such as angiogenesis and metastasis on a genetic level and at their earliest stages, offers a profoundly different approach to that taken currently, and promises to greatly enhance the treatment of cancers.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: A targeted drug design approach to the discovery and evaluation of new chemopreventive agents
Funder: Cancer Research UK

Abstract: Background: The Government and NHS are placing a significant emphasis on reducing the risk of developing cancer as an alternative to focusing on treatments alone. In this context, the role of certain dietary components in protecting against developing cancer is supported by epidemiological evidence. Detailed biological studies on chemopreventive natural products have identified convergent effects on biochemical pathways. Many thiol-reactive chemopreventive agents interact with the cysteine-rich protein Keap1, thereby blocking the ubiquitination of its binding partner, the transcription factor Nrf2. Accumulated Nrf2 up-regulates the activity of antioxidant response element genes involved in cytoprotective responses. Relevance to cancer: An understanding of this and other pathways should allow the next generation of cancer preventive agents to be rationally designed to interact with particular molecular targets. The overall objectives of such a research effort are to identify selective, potent and safe molecules that reduce the risk of cancer. Such agents would initially be targeted to those known to be at risk of particular cancers (e.g., family history, environmental factors) but, if proven to be safe and effective, could ultimately be used in a wider population. Aims and objectives: The objectives of this project are to discover (through virtual and physical screening, molecular modelling and synthesis) and evaluate novel agents capable of up-regulating the activity of the transcription factor Nrf2 by inhibiting its protein-protein interaction with Keap1. Advantages of this approach include: (a) such ligands do not need to be thiol-reactive electrophiles, (b) interaction with the target is reversible, (c) interaction with off-target nucleophiles is diminished and (d) dose response profiles may be more predictable. These are important considerations for molecules that will require long-term administration to healthy individuals. Outline plan of research: This project makes use of information from x-ray crystallography on the Kelch domain of Keap1 alone and in complex with peptides from the Nrf2 Neh2 domain. Based on preliminary data, small molecule fragments and virtual compound libraries will be screened in silico to identify potential ligands that interact with the Keap1 binding site. Compounds will then be prioritised for purchase or in-house synthesis. ELISA and fluorescence polarisation assays will be developed for assaying potential inhibitors of the protein-protein interaction. We will also use established cell based reporter assays to determine the functional activity of compounds on Nrf2-dependent gene expression. Feed back of SAR results will inform the design and synthesis of further ligands. Lead molecules will be screened to establish that they are non-cytotoxic and then progressed to preclinical and clinical studies.


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