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					Liverpool Cancer Research UK Centre

                    Victoria Gallery and Museum
                           University of Liverpool
                                  May 14th 2012



    ANNUAL MEETING
              2012
Contents

Schedule for the day                           4
Guest Speakers                                 5
University of Liverpool Speakers               6
Short Talks                                    9
Poster Competition Abstracts                   11
Liverpool CRUK Centre 2011-12                  26
Attendees List                                 30




Front Cover Image: Martina Angi, Liverpool Cancer Research UK Centre Clinical Fellow with
Lauren Dodgson at Sefton Park Race for Life 2011
                                                                                            1
  Liverpool Cancer
 Research UK Centre
Annual Meeting 2012
Schedule
9.00-9.20     Coffee & Registration

9.20-9.30     Introduction. John Neoptolemos, Centre Director

9.30-10.00    Management of muscle invasive bladder cancer: Opportunities for
              translational studies.
              Syed Hussain, Clinical Senior Lecturer and Consultant,
              University of Liverpool

10.00-10.30   Short Talks (see p9).

10.30-11.00   Tea/Coffee Break

11.00-11.45   The novel alkylating anthraquinone Alchemix induces replication
              damage and cell death independently of ATM and p53.
              Grant Stewart, School of Cancer Sciences,
              University of Birmingham

11.45-12.15   Unity and diversity in tumour stromal cell function.
              Andrea Varro, Professor of Physiology, University of Liverpool

12.15-13.15   Poster Session

13.15-14.00   Lunch

14.00-14.45   Targeted therapies for colorectal cancer.
              Alberto Bardelli, Institute for Cancer Research and Treatment,
              University of Turin

14.45-15.15   Short Talks (see p9).

15.15-15.45   Tea/Coffee Break

15.45-16.15   The role of clathrin in mitotic spindle organisation.
              Stephen Royle, Cancer Research UK Career Establishment
              Award Fellow, University of Liverpool

16.15-17.00   BRAF and RAS signalling in melanoma.
              Richard Marais, Paterson Institute for Cancer Research,
              Manchester

17.00-18.30   Posters, Awards, Pizza and Drinks
11am - Grant Stewart




                                                                                                               Guest Speakers
The novel alkylating anthraquinone Alchemix induces replication
damage and cell death independently of ATM and p53.
Dr Grant Stewart is a CR-UK Career Development and Lister Institute
Fellow, who runs a laboratory within the College of Medicine and
Dentistry, School for Cancer Sciences, University of Birmingham.
The principle focus of the research ongoing within Grant’s laboratory
is understanding how the cellular recognises and responds to genetic
damage, such as DNA breaks and DNA inter-strand cross-links, which are
caused by exposure to ionising radiation and certain chemotherapeutic
drugs.

One of the primary research goals of the laboratory is to understand how
the ubiquitin and SUMO system function to regulate the recruitment of repair proteins to sites of DNA
damage and how defects in this pathway contribute the development of human disease and cancer.

                                                                     2pm - Alberto Bardelli
                                                          Targeted therapies for colorectal cancer.
                           Professor Alberto Bardelli is Professor of Oncological Sciences at the
                           University of Torino School of Medicine and Director of the Laboratory of
                           Molecular Genetics at the Institute for Cancer Research and Treatment in
                           Turin, Italy.
                           Alberto and his laboratory in Turin have pioneered the use of AAV-medi-
                           ated homologous recombination to generate human isogenic cell-lines
                           harboring individual cancer mutations and their ability to accurately
                           predict responses to appropriately targeted agents in patients. Recent work
                           from Alberto’s lab has had a transforming effect on current clinical practice
                           in the field of personalised medicine. Alberto and colleagues discovered
that K-Ras or B-Raf mutations in colon cancer impart resistance to novel EGFR-targeted therapies,
these discovery were rapidly translated into genetic testing of colon cancer patients prior to receiving
such therapies. A future focus of his lab is to define other resistance mechanisms in patients and find
appropriately tailored drug combinations that target them.


4.15pm - Richard Marais
BRAF and RAS signalling in melanoma.
Professor Richard Marais is Director of the
Paterson Institute for Cancer Research in
Manchester.
Richard is a world-leading expert on the
underlying causes of melanoma, the most serious
form of skin cancer. Much of his work has focused
on how the protein BRAF triggers cancer, which is
faulty in more than half of all melanomas. Damage
to the protein locks it in an active form that drives
cell growth that ultimately leads to cancer.

This work has already led to the discovery of potential new drugs to treat skin cancer that are now
showing promise in clinical trials.
                                                                                                           5
9.20am
Introduction from John Neoptolemos
                                           Professor John Neoptolemos is Director of the
                                           Liverpool Cancer Research UK Centre, The Owen and
                                           Ellen Evans Chair of Cancer Studies, Professor of Sur-
                                           gery at the University of Liverpool and Consultant
                                           Surgeon at the Royal Liverpool University Hospital.
                                           John leads one of the most successful clinical and
                                           academic surgical programmes in the UK.

                                           His specific area is clinical and translational research
                                           of pancreatic cancer.
John is a Fellow of the Academy of Medical Sciences and a National Institute for Health Research
Senior Investigator.




                                                                 9.30am
                                                          Syed Hussain
                           Management of muscle invasive bladder cancer:
                                  Opportunities for translational studies

Syed is a Clinical Senior Lecturer and Consultant in medical
oncology.
His major areas of interest include genitourinary oncology,
translational oncology, early drug development, and clinical
trials.
He has been an investigator on various national studies
including the pivotal bladder study BC2001which is the
largest randomised trial in muscle invasive bladder cancer
comparing radiotherapy to chemo radiotherapy (James,
Hussain Hall et al NEJM April 2012).
He is using the success of the Liverpool Pancreas BRU as a
template to continue development of translational research
programme in urological oncology.
There is an exciting future ahead for academic medicine at the
University of Liverpool, with known strengths in clinical trials
and translational research and Dr. Hussain aims to complement that by initiating new clinical
and translational studies to enhance the portfolio further.
This will no doubt provide local patients more choices and treatment opportunities.




                                                                                                      6
11.45am




                                                                                                            Liverpool Speakers
Andrea Varro
Unity and diversity in tumour stromal cell function
Professor Andrea Varro MD, PhD, Professor of Physiology, Institute of Translational Medicine,
University of Liverpool.
Andrea graduated in medicine from the University of Szeged,
Hungary and was awarded a PhD, funded by the Hungarian
Academy of Science, by the Semmelweiss University of Budapest,
Hungary, in 1985.
She has long standing research interests in progastrin and its
derivatives, Helicobacter pylori infection, and preneoplastic
changes in the stomach. Her recent work focuses on the tumour
microenvironment in the stomach and oesophagus and in
particular on the contribution of myofibroblasts.
She has published more than 160 scientific papers and was
awarded a Hetenyi Geza medal for her outstanding contribution to
translational research in the field of gastroenterology.




                                                                        3.45pm
                                                                 Stephen Royle
                            The role of clathrin in mitotic spindle organisation
Dr Stephen Royle is a Senior Lecturer in the Department of Cellular & Molecular Physiology,
Institute of Translational Medicine, University of Liverpool.
                                 Steve developed an interest in clathrin-mediated membrane
                                 trafficking during his PhD in Pharmacology at University of
                                 Cambridge (1999-2002).
                                 He moved to the MRC Laboratory of Molecular Biology for his
                                 post-doctoral training with Leon Lagnado.
                                 While worked on membrane trafficking at synapses, he made the
                                 serendipitous discovery of a new function for clathrin in mitosis.
                                 In 2006, he came to Liverpool to set up his own group and was
                                 awarded a Career Establishment Award by Cancer Research UK in
                                 2007.

                                 Steve’s lab is interested in the basic molecular biology of the cell
                                 and is focussed on the processes of membrane trafficking and
                                 mitosis, and how these processes are altered in cancer.




                                                                                                        7
  Short Talk and
Poster Competition
     Abstracts


 Poster prizes: 2 x £300 conference travel awards

Poster Prize Judges: Eithne Costello, Judy Coulson,
     Sarah Coupland, Ian Prior, Carlos Rubbi,
          Violaine Sée, Nikolina Vlatkovic
10am - Andrew Schache




                                                                                                                          Short Talks
Validation of a Novel Diagnostic Standard in HPV Positive
Oropharyngeal Squamous Cell Carcinoma
Andrew G Schache1,2, Triantafilos Liloglou1, Janet M Risk1, Terence M Jones1,2, Xiao-Jun Ma3, Hongwei
Wang3, Son Bui3, Yuling Luo3, Philip Sloan4, Richard J Shaw1,2, Max Robinson4
1
  Department of Molecular & Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool,
Daulby Street, Liverpool, L69 3GN, United Kingdom
2
  Regional Head & Neck Surgery Unit, Aintree University Hospitals NHS Foundation Trust, Longmoor Lane, Liver-
pool, L9 7AL, United Kingdom
3
  Advanced Cell Diagnostics, Hayward, California, USA
4
  Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Framlington Place, Newcastle
upon Tyne, NE2 4BW, United Kingdom
Purpose: The “gold standard” for HPV testing in Oropharyngeal SCC (OPSCC) is demonstration of
transcriptionally active high-risk HPV in fresh tumour tissue. For clinical utility, testing has focused
on formalin-fixed paraffin-embedded (FFPE) tissue at the expense of sensitivity and specificity. This
study determines the performance of a novel RNA in situ hybridisation test applied to FFPE.
Materials & Methods: FFPE tissue from 79 OPSCC was tested using High-Risk HPV RNAscope. Ana-
lytical accuracy and prognostic capacity was determined by comparison with qRTPCR on matched
fresh-frozen tumour samples.
Results: RNAscope displayed noteworthy sensitivity (97%) and specificity (93%) against the refer-
ence test. Kaplan-Meier estimates of DSS (p=0.002) and OS (p<0.001) by RNAscope were compara-
ble to the reference test (DSS, p=0.006, OS, p=0.002) and superior to routine clinical tests.
Conclusion: High-Risk HPV RNAscope demonstrates excellent analytical and prognostic perform-
ance against the “gold standard”, raising the possibility that this test could be adopted as the clinical
standard in HPV-OPSCC diagnostics.


10.15am - Tanzeela Khalid
Volatile markers in urine for the detection of prostate and
bladder cancer
T. Y. Khalid1, N.M. Ratcliffe2, B. De Lacy Costello2, R. Ewen2, P. White2, A. R. Persad3, D. Gillatt4 & C.
S. J. Probert1
1
  Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, UK, 2Centre
for Research in Analytical, Material and Sensor Sciences, University of the West of England, Bristol,
3
  United Bristol Healthcare Trust, University of Bristol, 4Bristol Urological Institute, North Bristol NHS Trust.
Prostate cancer is the most common male malignancy in the UK and >10,000 patients are
diagnosed with bladder cancer in the UK annually. There are no reliable screening tests for
these cancers. Our aim was to identify volatile markers in urine that may aid diagnosis for
these malignancies, especially for more aggressive tumours that will require medical
intervention.
Urine samples from patients with prostate cancer (n = 58), bladder cancer (n = 24), and
non-cancerous age-matched controls that had other urinary tract problems (n = 74) were
tested using gas chromatography interfaced to a heated metal oxide sensor. Seventy-five
percent of samples were used to train an artificial neural network (ANN) for pattern
recognition. Testing the ANN on the remaining 25% of samples correctly classified 78.1%
and 96.3% of patients for prostate and bladder cancer, respectively. Thus the
GC-sensor-ANN has potential for facilitating the diagnosis of these cancers.

                                                                                                                      9
2.45pm - Dean Hammond
Quantitative proteomic analysis of human Isogenic Colorectal
cancer cell-lines harbouring oncogenic K-Ras mutations
Dean Hammond, Craig Mageean, Ian Prior and Michael Clague.
Department of Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69
3BX.
Colorectal cancer (CRC) accounts for ~15% of diagnosed cancers in the UK and is a
leading cause of cancer-related mortality. K-Ras is commonly mutated in various forms,
in CRC. Substitution of Glycine at position 12 or 13 for Valine or Aspartic acid, for
example, renders K-Ras constitutively active. Clinical data suggest these mutations are
not equal as they differentially affect patient survival rate and resistance to therapies;
for example, CRC patients harbouring G12V or G12D K-Ras mutations are unresponsive
to Cetuximab, whereas G13D K-Ras mutated CRCs respond. The reasons for these
observations are unknown. We have performed SILAC and quantitative (phospho)
proteomics on a novel panel of model K-Ras mutated CRC cell-lines (Isogenic, SW48) in
order to obtain a snapshot of their basal intracellular signalling activity relative to
wild-type cells. Several interesting mutation-specific changes in both protein
abundance and activity were discovered (e.g. DCLK1, AKAP12).


3pm - Ryan Baron
Dissecting the role of Aurora B in the regulation of cell cycle
progression
Ryan D. Baron1,2, Ricardo Nunes-Bastos2, John P. Neoptolemos1, Francis A. Barr2.
1
  Liverpool Cancer Research UK Centre, Department of Molecular and Clinical Cancer Medicine,
University of Liverpool, Liverpool UK. 2Department of Biochemistry, University of Oxford, Oxford OX1
3QU.
Aurora kinases are essential regulators of cell division, and their dysregulation is thought to
act as a driver in a number of cancers. Accordingly, potential new anti-cancer drugs
currently in early stage clinical trials have targeted the Aurora kinases. Despite this
progress, a number of aspects of Aurora kinase regulation remain mysterious.
In particular the complex pattern of spatial and temporal control of Aurora-B activity is
only partially understood. Here we have investigated this problem, and describe how the
kinesin motor protein MKlp2 controls Aurora-B localization in dividing cells. Biochemical
analysis of MKlp2 complexes purified from cells at different times in mitosis identifies a
conserved protein complex we term MATA (MKlp2 Aurora-B Targeting Activity). These
findings indicate that MKlp2 and MATA are crucial components required for Aurora-B
localization in dividing cells. Disruption of this MKlp2-dependent transport process results
in the failure of cell division and promotes cell death or genomic instability.




                                                                                                        10
                 12.15pm and 5pm - Poster Sessions




                                                                                                                           Poster Competition
1. Elucidation and Investigation of Mechanisms and Consequences of MDM2-NME2 Interaction
on Cell Motility and Invasion in Renal Cell Carcinoma

Shie Hong Chang, Radosław Polański, Maria Maguire, Nikolina Vlatković and Mark T. Boyd
p53/MDM2 group, Cancer Research Centre, 200 London Road, Liverpool L3 9TA

MDM2 is a proto-oncogene well known for its role as a negative regulator of the p53 tumour suppres-
sor. Studies have shown that co-upregulation of MDM2 and wild-type p53 is linked with reduced dis-
ease specific survival in renal cell carcinoma (RCC) 1. Moreover, MDM2 expression has been shown to
promote cell motility and invasiveness in RCC cells in a p53- and RING finger- independent manner,
suggesting a role for protein-protein interactions in mediating this effect 2. In fact, MDM2 binds directly
to the metastasis suppressor NME2 (Non-metastatic protein 2) and abrogates the motility suppressing
activity of NME2 3. However, the mechanism of action for this remains unclear. NME2 is a nucleoside
diphosphate kinase (NDPK) essential for maintaining cellular pools of nucleoside triphosphates. Since
NME2 kinase domain spans majority of the relatively small protein, we hypothesise that MDM2 may
promote cell motility by regulating the motility suppressing activity of NME2 through modulating NME2-
encoded NDPK activity.
1
  Noon AP, Polanski R, El-Fert AY, et al. BJU Int 2011.
2
  Polanski R, Warburton HE, Ray-Sinha A, et al. FEBS Lett 2010;584(22): 4695-702.
3
  Polanski R, Maguire M, Nield PC, et al. Carcinogenesis 2011;32(8): 1133-42.
2. Removal of Epidermal Growth Factor (EGF) induces the formation of interdigitating ‘Actin Fin-
gers’ in MCF10A cells.

Yvonne Tang, Sylvie Urbé, Judy M Coulson and Michael J Clague.
Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool
Abstract
MCF10A is a near normal mammary epithelial cell line with a diploid karyotype1 used to model the pro-
gression of breast cancer2. Isogenic cell lines with cancer-associated mutations have been developed
based on MCF10A. One example is the EGFR ΔE746-A750 cell line containing a non-small cell lung
cancer associated point mutation in exon 19. Patients with this EGF receptor (EGFR) mutation are par-
ticularly susceptible to EGFR tyrosine kinase inhibitors (eg. Iressa) due to the constitutively activated
EGFR3.
Initial experiments were carried out to establish growth conditions for the MCF10A. Normally MCF10A
is cultured in growth medium supplemented with horse serum, EGF, insulin, hydrocortisone and cholera
toxin. We report here a novel structure: interdigitating cellular protrusions positive for actin between
MCF10A cells upon removal of EGF (henceforth referred to as ‘Actin Fingers’). This result was replicat-
ed using Iressa in MCF10A but not in the EGFR ΔE746-A750 cell line implying a role for the EGFR.
References:
1.
   Soule et al, Cancer Research (1990) 50:6075-6086
2.
   Pauley et al, Eur J Cancer Prev (1993) 2 Suppl 3:67-76
3.
   Rosell et al, Clin Cancer Res (2006) 12(24):7222-7231
3. Exploitation of the chick embryonic microenvironment to reprogram MYCN-amplified neurob-
lastoma cells to a benign phenotype, lacking detectable MYCN expression
Rachel Carter[1], Dhanya Mullassery[3], Violaine See[2], Sokratis Theocharatos[1], Barry Pizer[1,4],
Paul D. Losty[1,3] , Edwin Jesudason[1], Diana Moss[1]
[1]Institute of Translational Medicine, [2]Institute of Integrative Biology, Centre for Cell Imaging, University of
Liverpool [3]Department of Paediatric Surgery, Alder Hey Children’s NHS Foundation Trust, Alder Hey Children’s
Hospital, Liverpool [4]Department of Paediatric Oncology, Alder Hey Children’s NHS Foundation Trust, Alder Hey
Children’s Hospital, Liverpool

Neuroblastoma is a paediatric cancer of the sympathetic nervous system, of which those with MYCN
amplification have the worst prognosis. Tumours can undergo spontaneous regression, most frequently
in the youngest patients. This led us to hypothesise that an appropriate embryonic environment may be
capable of differentiating or reprogramming neuroblastoma cells. We have shown that MYCN-amplified
Kelly cells injected into E3 chick embryos integrate into neural crest-derived tissues. In neural environ-
ments, such as the sympathetic ganglia and enteric nervous system, some Kellys differentiate and show
reduced proliferation, whereas in non-neural structures, like the meninges and tail, Kellys form more
rapidly-dividing clumps. Crucially, Kellys in the sympathetic ganglia have undetectable MYCN expres-
sion, in contrast to cells in other areas. Downregulation of MYCN is dependent on continuous and
direct interaction with the sympathetic ganglion environment. This supports our hypothesis, in that the
cells’ behaviour and gene expression have been altered by the sympathetic ganglia’s microenvironment.

                                                                                                                      11
4. Dissecting the role of Aurora B in the regulation of cell cycle progression
Ryan D. Baron1,2, Ricardo Nunes-Bastos2, John P. Neoptolemos1, Francis A. Barr2.
1
 Liverpool Cancer Research-UK Centre, Department of Molecular and Clinical Cancer Medicine, University of
Liverpool, Liverpool, UK. 2Department of Biochemistry, University of Oxford, Oxford OX1 3QU.

Aurora kinases are essential regulators of cell division, and their dysregulation is thought to act
as a driver in a number of cancers. Accordingly, potential new anti-cancer drugs currently in early
stage clinical trials have targeted the Aurora kinases. Despite this progress, a number of aspects of
Aurora kinase regulation remain mysterious. In particular the complex pattern of spatial and tempo-
ral control of Aurora-B activity is only partially understood. Here we have investigated this problem,
and describe how the kinesin motor protein MKlp2 controls Aurora-B localization in dividing cells.
Biochemical analysis of MKlp2 complexes purified from cells at different times in mitosis identifies
a conserved protein complex we term MATA (MKlp2 Aurora-B Targeting Activity). These findings
indicate that MKlp2 and MATA are crucial components required for Aurora-B localization in dividing
cells. Disruption of this MKlp2-dependent transport process results in the failure of cell division and
promotes cell death or genomic instability.
5. Identification of Deubiquitinases Involved in Regulation of ß-catenin

Jia-Lih Wong, Judy Coulson, Sylvie Urbé, Michael Clague
Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool

Abstract:ß-catenin is a key component of the Wnt signalling pathway and adherens junction. It is
known that ß-catenin and other Wnt Signaling pathway components can be ubiquitylated, affecting
their stability and/or signalling activity. Ubiquitylation is a reversible post-translational modification,
where the ubiquitin moiety attached to a substrate can be removed by deubiquitinases (DUBs). To
investigate the roles of DUBs in the regulation of ß -catenin, two DUB siRNA library screens were
performed in A549 and SW480 cells respectively. BAP1 and USP6 were identified as potential ß-
catenin regulators in the two screens respectively. BAP1 depletion resulted in the loss of ß-catenin
in A549 and MCF7 cells, while its overexpression in MCF7 cells resulted in increased level of
ß-catenin. This effect of BAP1 depletion was not observed in SW480 and HEK293T cells. Deple-
tion of USP6, resulted in accumulation of higher molecular weight forms of ß-catenin in SW480
and an apparent decrease in ß-catenin levels in HEK293T cells, whilst overexpression of USP6 in
HeLa cells led to an increase in ß-catenin levels. These observations suggest roles for BAP1 and
USP6 as positive regulators of ß-catenin. However, the effects of these DUBs on ß-catenin are not
universal in all cell lines tested. Together, these results indicate differential regulation of ß-catenin
by different DUBs in a cell type-dependent manner.
6. Medulloblastoma cells plasticity is sensitive to oxygen levels
Shahidipour H1, Papayabalakrishna J2, Pizer B2 and Sée V1
University of Liverpool, Centre for cell imaging, Crown Street, Liverpool L69 7ZB, UK. 2Alder Hey Children’s
1

NHS Foundation Trust, Liverpool, L12 2AP, UK

Aim: The purpose was to investigate the role of hypoxic environment in medulloblastoma cell plas-
ticity and its effect on cell dedifferentiation and chemoresistance.
Methods: We used three MB and two Atypical Teratoid/Rhabdoid Tumor (AT/RT) cell lines. Im-
munocytochemistry was performed to characterise level of differentiation. Neurosphere formation
assay was performed and we submitted the spheres to differentiation using retinoic acid. Differenti-
ated and de-differentiated cells were treated with etoposide and cell viability assays performed.
Results: The three MB cell lines could form neurospheres however AT/RT cells were unable to form
tumour spheres. We demonstrated that the neurospheres could be subjected to steps of differen-
tiation and de-differentiation, leading to loss or gain of stem cell or neuronal markers accordingly.
We investigated the role of hypoxia in the re-programming process where hypoxia increased cell
resistance to etoposide.
Conclusion: Our findings on the influence of the tumour microenvironment on drug sensitivity have
implications on the development of new therapeutic strategies to target brain tumour cells.
7. Growth control by the actin cytoskeleton: transcriptional targets of MRL/SRF signalling
V. Jonchère, L. Dodgson, and D. Bennett
Institute of Integrative Biology, University of Liverpool, Biochemistry and Cell Biology, Liverpool U.K.

MRL proteins act as key convergence points linking signals from GFR (Growth Factor Receptor) to
regulators of the actin cytoskeleton and activation of SRF, a mitogenic-responsive transcription fac-
tor. MRL signalling is a novel GFR-responsive pathway controlling tissue growth; deregulated MRL/
SRF is involved in tumourigenesis and cancer progression.
Here, we investigate how MRL proteins and the actin cytoskeleton regulate SRF-mediated gene
                                                                                                               12
expression in D. melanogaster to promote hyperplastic growth.
In vivo, we are investigating the effect of perturbation of the MRL signaling pathway on SRF-activity us-




                                                                                                                            Poster Competition
ing an SRF-reporter gene.
 In vitro, we are identifying the transcriptional targets of the MRL/SRF signalling pathway using RNA-
sequencing, Chip-sequencing & bioinformatics. The analysis of MRL/SRF targets will allow us to identify
the key genes & hub and determine their contribution to MRL-mediated tissue overgrowth.
This study will allow us to better understand the mechanisms by which MRL proteins control actin
cytoskeleton dynamics and SRF activation. The identification of MRL/SRF targets and their phenotypic
outputs will help us to improve our knowledge of the molecular targets for therapeutic intervention
against cancer.
8. USP21, a centrosome and microtubule associated deubiquitinase, controls microtubule
dynamics.
Claire Heride, Han Liu, Michael Clague and Sylvie Urbe
Cellular and Molecular Physiology, Institute of Translational Medicine, University, Crown Street, Liverpool L69 3BX,
UK

Deregulation of microtubule dependent-processes leads to a wide range of pathologies such as neuro-
degenerative diseases, ciliopathies and cancer.
Here, we show that the deubiquitinase Ubiquitin Specific Protease 21 (USP21) localizes to the centro-
some and to a subset of microtubules. Furthermore biochemical experiments coupled to microscopic
observations indicate that USP21 contains microtubule interacting-motifs. Altogether these data strongly
suggest a role of USP21 in microtubule dependent-processes.
After USP21 depletion in various cell lines, we show that USP21 is involved i) in the re-establishment
of a radial array of microtubules during recovery after cold-induced depolymerisation in A549 cells, ii) in
the induction of nerve growth factor-induced neurite outgrowth in PC12 cells, and iii) in the formation of
primary cilia in A549 and RPE1-hTERT cells.
Finally, in order to identify USP21 interacting partners, yeast-two-hybrid experiments have been per-
formed and several proteins isolated. Validation of these interactions in human cells is ongoing.
9. Barriers to recruitment in Head & Neck cancer trials
Geetinder Kaur2, Catrin Tudur-Smith3, Richard Shaw1, Paula Williamson3
1
  Head & Neck Surgery, Department of Molecular & Clinical Care Medicine, University of Liverpool. Oral & Maxillofa-
cial/ Head& Neck Surgery, Aintree University Hospitals NHS Foundation Trust
2
  MRC North West Hub for Trials Methodology Research (NW HTMR), Institute of Translational Medicine, University
of Liverpool
3
  MRC NW HTMR and Department of Biostatistics, University of Liverpool

Aim: Head and Neck cancer trials recruit the fourth highest number of patients compared with other tu-
mour sites however recruitment has lagged in surgical trials. In this study we aim to explore the barriers
to recruitment in three surgical trials: SEND, PET-Neck & HOPON.
Method: We conducted a survey of recruitment experience of clinical teams involved in recruiting to the
three trials. We identified barriers to recruitment in terms of operating in relation to the trial, site, patient,
clinical team and information and consent.
Results:The highest scoring barriers to recruitment were reported as: patients refuse consent, lack of
time in clinic to recruit, consultant surgeon’s preference for one arm of trial, lack of research nurse, lack
of funding for extra costs of treatment and excess administrative burden.
Conclusions: There are unique issues in trials of surgical interventions. Possible interventions are dis-
cussed.

10. The Role of Reversible Ubiquitination in EGF signalling
Ewan MacDonald, Sebastian Hayes, Sylvie Urbé and Michael Clague.
Cellular and Molecular Physiology, Institute of Translational Medicine, University, Crown Street, Liverpool L69 3BX,
UK

Plasma membrane (PM) localised Epidermal growth factor receptor (EGFR) activation leads to multiple
downstream signalling events culminating a variety of signalling outputs, including changes in transcrip-
tion and proliferation. Signals must be transduced from the PM into the cytoplasm and nucleus, which is
achieved through protein translocations. An example being the ERK kinase that moves into the nucleus
from the cytoplasm upon EGF stimulation. Recent work has described an extensive mobilisation of the
ubiquitination machinery in EGF signalling, including the deubiquinatase (DUB) family of enzymes that
remove ubiquitin from a substrate. To identify DUBs that are effectors of EGF signalling we used a GFP-
DUB library to look at changes in localisation upon EGF application. The study identified UCHL5, YOD1
and USP46 as novel effectors of EGF signalling. Work is on going into understanding how EGFR signal-                   13
ling affects the relationship between these DUBs and their substrates in a dynamic manner.

11. VEGFxxxb protein expression is downregulated in monosomy 3 (M3) uveal melanoma (UM)
Andrew Dodson1, Bertil Damato2, Sarah Coupland1 and Helen Kalirai1
1
 Pathology, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University
of Liverpool, Liverpool, UK
2
    Liverpool Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK
Purpose: Metastatic spread of UM occurs haematogenously and almost exclusively in patients whose
tumour shows loss of one copy of chromosome 3 (M3). Tumour growth and metastasis requires angio-
genesis, mediated by factors such as Vascular Endothelial Growth Factor-A (VEGF-A). We determined
pro- and anti-angiogenic VEGF-A protein levels in UM and correlated these with clinical and histological
features.
Method: Expression of pan-VEGF and anti-angiogenic VEGFxxxb; CD68 and CD163 (assessing
tumour-associated macrophages (TAMs); and CD34 (assessing tumor vasculature) were evaluated im-
munohistochemically in 50 UMs. The percentage and intensity of tumour cells stained (staining index;
SI) was scored by three independent assessors. All data were tested in SPSS.
Results: pan-VEGF and VEGFxxxb were expressed in both tumour cells (TCs) and TAMs. The
VEGFxxxb SI in the TCs was significantly lower in M3 UMs than in disomy 3 UMs (Spearman’s,
p<0.001).
Conclusion: Diminished angiogenic inhibition may contribute to the growth and metastasis of UMs.

12. Database mining analysis of combined proteomic and microarray experiments: Modelling
APC loss in colorectal carcinogenesis, identifying the importance of Nucleolin.
PJ Skellorn, S Ibrahim, F Song and JR Jenkins.
Department of Gastroenterology, Institute of Translation Medicine, University of Liverpool, Crown Street, L69 3GE.

Abstract: Colorectal cancer is the second most common cause of cancer-related death in the UK.
AhCre+ APCfl/fl mice are an established model of colorectal carcinogenesis. The purpose of this study
was to use data base mining strategies to study combinations of different types of complex data: LC-
MS/MS iTRAQ proteomic and microarray profiles generated from the intestinal crypt epithelium of the
AhCre+ APCfl/fl mice. The Metacore program was selected as it is the only available platform that will
perform such a comparison. The power of this approach is demonstrated by the identification of Nu-
cleolin as a potentially important novel drug target for colorectal cancer. This analysis also highlighted
the differential contributions, array studies tended to identify initiating factors in pathways, where as
the proteomic data identified more endpoints and ultimately the effect on the cell cycle, in the case of
Nucleolin.

13. Effect of long term hypoxia on cell cycle progression and chemoresistance in paediatric
tumours
Catherine Heyward*, Carol Fan*, Mike White^, Heather McDowell§, Barry Pizer§, Paul D Losty**
and Violaine Sée*.
* Centre for Cell Imaging, Biosciences Department, University of Liverpool, Crown Street, Liverpool L69 7Z
^ Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT
** Academic Paediatric Surgery, University of Liverpool, Alder Hey, Liverpool L12 2AP
§ Alder Hey Children’s NHS Foundation Trust, Liverpool L12 2AP

Hypoxia occurs in the core of solid tumours, and is crucially linked with tumour aggressiveness and
poor prognosis. We investigated the response of paediatric tumour cell lines to hypoxia to elucidate the
relationship between hypoxia and chemoresistance, which could aid the development of better treat-
ments and improve patient outcome.
Neuroblastoma (SK-N-AS) and Medulloblastoma (D283) cells were treated with chemotherapeutic
agent etoposide, after growth in normoxia, or long-term (5 days) or short-term (1 day) hypoxia. We as-
sessed cell viability and cell division by MTT assay and flow cytometry, and gene induction by qPCR.
Medulloblastoma cells cultured long-term in hypoxia displayed impaired cell cycle arrest and reduced
sensitivity to etoposide, whereas neuroblastoma cells did not show altered chemoresistance in hypoxia.
Surprisingly neither cell type exhibited induced multidrug resistance (MDR1) expression. We now aim to
elucidate the molecular mechanisms involved in the ability of particular cell types to develop chemore-
sistance in chronic hypoxia.

14. Diagnosis of Pancreatic Cancer with a Cytokine Biomarker Panel
Victoria E Shaw1, Claire Jenkinson1, Brian Lane2, Bill Greenhalf1,2, John P Neoptolemos1,2 and
Eithne Costello1,2
                                                                                                                     14
1
 Liverpool Cancer Research-UK Centre, Department of Molecular and Clinical Cancer Medicine, University of Liv-




                                                                                                                               Poster Competition
erpool, Liverpool, UK. 2Liverpool National Institute for Health Research Biomedical Research Unit, Department of
Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.

Introduction: Pancreatic cancers (PDAC) presentation is similar to benign diseases where bilirubin lev-
els are also increased. The PDAC biomarker, CA19-9, is increased by benign biliary obstruction (BBO)
and chronic pancreatitis (CP), reducing specificity for PDAC. The aim is to identify a cytokines, chemok-
ines and growth factor (CCGF) panel to detect PDAC from CP and BBO, with greater sensitivity/specifi-
city than CA19-9 alone.
Patients/Methods: PDAC (n=122), CP (n=45) and BBO (n=26) patient serum was analysed for 27
CCGFs. Following normalisation/log transformation and feature finding, logistic regression was under-
taken to identify the optimum panel and validate in two independent data sets.
Results/Conclusion: ROC curve analysis revealed a 4 CCGFs plus CA19-9 panel (AUC=0.83, sensitiv-
ity=70%, specificity=89%) that was significantly better than CA19-9 alone (AUC=0.73, sensitivity=77%,
specificity=63%) at distinguishing PDAC from benign disease (p=0.0027). Two independent sample
sets confirmed this. Biomarker panels can distinguish PDAC from benign pancreatic disease with better
specificity than CA19-9 alone.

15. Prognostic testing of uveal melanoma (UM)
Marcela Baudo1, Helen Kalirai1, Bertil E. Damato2, Sarah E. Coupland1.
1.
  Pathology, Department of Molecular & Clinical Cancer Medicine, University of Liverpool   2.
                                                                                                Liverpool Ocular Oncol-
ogy Centre, Royal Liverpool University Hospital NHS Trust, Liverpool.

Purpose: Metastasis from UM occurs almost exclusively with tumours showing chromosome 3 loss. We
routinely use multiplex ligation-dependent probe amplification (MLPA) to detect chromosome 1p, 3, 6p,
6q, 8p, and 8q abnormalities in UM. The purpose of this study was to correlate our MLPA results with
other risk factors and metastatic death.
Methods: MLPA-data from >450 UM cases were examined for chromosomal imbalance frequencies, and
correlated with tumour size, survival time and mortality.
Results: Ten-year disease-specific mortality was 0% in UM with no chromosome 3 loss, 55% in UM
with chromosome 3 loss but no chromosome 8q gain, and 71% in UM showing combined chromosome
3 loss and 8q gain. A wide variety of MLPA results were demonstrated, suggesting that chromosomal
abnormalities in UM accumulate in a variable sequence.
Conclusions: These results support the continued use of MLPA for routine clinical prognostication, com-
bining genetic data with clinical and histological risk factors

16. PNUTS-PP1 associates with transcriptionally active sites on interphase chromosomes and is
required for cell survival
Louise Rebecca Rawling1, Anita Lucaci1, Andrey Rudenko2, Peter Glenday1, Luke Alphey2,
Daimark Bennett1.
1
  Inst Integrative Biology, Univ Liverpool, Liverpool; 2 Dept Zoology, Oxford University, Oxford.
Reversible phosphorylation of structural and regulatory proteins is an important mechanism of regulat-
ing spatial and temporal patterns of gene expression. Protein Phosphatase 1 (PP1) is found at many
sites on Drosophila polytene chromosomes where it has important roles in controlling gene expression
and chromatin structure. PP1 is targeted through interaction with a variety of regulatory subunits, which
are thought to modify PP1’s activity towards specific substrates. We describe the in vivo role of PNUTS
(PP1 Nuclear Targeting Subunit), one of the most abundant PP1-binding proteins in the mammalian
nucleus. In proliferating tissues mutant cells become basally localised, express activated caspase and
undergo cell death. PP1 binding is essential for PNUTS function and they associate at active sites of
transcription in an RNA-dependant manner during interphase. We present here results from genetic
and cell biological experiments to identify potential substrates of PNUTS-PP1, which help to explain its
requirement in cell survival.

17. p53 analysis is a better predictor of prognosis than histology in pancreatic IPMN
J. A. Nicholson, L. Yan , R. Sutton , S. Harrison , H. Smart, J. Evans, M. Lombard, F. Campbell , J.
P. Neoptolemos and W. Greenhalf
NIHR Pancreas Biomedical Research Unit, Liverpool. Department of Molecular and Clinical Cancer Medicine, Insti-
tute of Translational Medicine.

INTRODUCTION: The role of p53 in the development and progression of IPMN is unclear.
METHODS: To investigate whether p53 mutational status can predict malignancy and outcome in IP-
MNs. 29 patients underwent resection for IPMN. p53 analysis was performed on pancreatic juice and
tissue samples.                                                                                                           15
RESULTS: There were 11 IPMNs, 7 IPMNs with invasive adenocarcinoma (IPMCs), 3 conventional
PDACs and 8 other benign entities. Eight patients died (median follow-up: 730 days). Tissue sample
p53 status correlated with histological malignancy (p=0.0005). Tissue p53 predicted survival in IPMN
and IPMC (p=0.0001) and was a better predictor of survival than conventional histology (p=0.01).
Tissue p53 mutational status matched that in juice in all but 2 cases (where mutation site lay within the
primers).
CONCLUSION: p53 mutational status can predict poor outcome in IPMNs, regardless of histological
grade. Pancreatic juice analysis could potentially be used to identify those patients with IPMN who
should be considered for resection.

18. Chick embryo xenografts (CEX) are a viable source of material for external quality assess-
ment (EQA) of HER2 immunocytochemistry (ICC) and fluorescence in-situ hybridisation (FISH).
Diana Moss (1), Andrew Dodson (2), Rebecca Jones (1) and Helen Kalirai (2)
 Department of Molecular and Cellular Physiology, University of Liverpool.
1.

2.
  Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, University of
Liverpool.

Purpose: Tissues that express antigens at a known and reproducible level and contain genes with a
pre-determined and stable copy number are essential for EQA. This study examines the feasibility of
using CEX for Human Epidermal Growth Factor Receptor 2 (HER2) EQA testing.
Materials and methods: Nodules formed by GFP labelled MDAMB231 (HER2 neg) or SKBR3 (HER2
3+) cells layered on the chorioallantoic membrane (CAM) of a fertilised chicken egg at E7/E8 were re-
moved, fixed and paraffin wax embedded after 7-9 days. Sections cut from the nodules underwent ICC
analysis of cytokeratin 19, Ki67, α smooth-muscle actin (αSMA) and HER2 protein.
Results: MDAMB231 nodules expressed CK19, Ki67; showed no expression of HER2; demonstrated
evidence of αSMA recruitment into the invasive nodules. In contrast, in a single experiment conducted
to date, SKBR3 cells failed to demonstrate convincing evidence of nodular growth on the CAM.
Conclusions: The CEX model can produce material suitable for use in EQA.

19. Investigating the role of MRL proteins in invasive border cell migration.
Lauren Dodgson, Eleanor Taylor, Daimark Bennett.
University of Liverpool,Institute of Integrative Biology, Liverpool, United Kingdom.

Several lines of evidence indicate that the Mig-10/RIAM/Lamellipodin (MRL) family of adapter proteins
transduce signals from growth factor receptors, via interactions with Ras GTPases and/or phospholip-
ids, resulting in changes in the actin cytoskeleton, lamellipodia protrusions, cell motility and altered cell
adhesion properties. Drosophila encodes only one MRL protein, encoded by pico, which we previously
showed to have a role in the regulation of actin dynamics. Here we report on the role of pico in invasive
border cell (BC) migration in the Drosophila ovary. During oogenesis, a pair of specialised cells differen-
tiates at the anterior end of the egg chamber, recruits four to eight additional cells to form a BC cluster.
After detaching BC’s make their way to the oocyte-nurse cell border, guided by redundant signalling
through the PDGF/VEGF receptor. Using live imaging approaches we are dissecting the requirement
for pico in the formation of actin-based protrusions and invasion in this system. This work points to the
involvement of MRL proteins in tumour cell invasion and metastasis.

20. Characterization of expression and function of carbonic anhydrase 2 in renal cell carcinoma
cells
Viktor Malec, Michael Clague
University of Liverpool, Laboratory of Physiology

The loss of function of von Hippel-Lindau (VHL) tumor suppressor is associated with development of
hypervascular tumors, exemplified by clear-cell type renal carcinoma (RCC). VHL plays a critical role
in regulation of adaptive responses of cells to low oxygen levels and pH changes as an adaptor pro-
tein enhancing proteosomal degradation of hypoxia inducible transcription factor (HIF). The plasma
membrane localised carbonic anhydrase (CA) isoform 9 is a well known VHL-HIF axis target involved
in intra-/extracellular pH regulation. Our data from large scale proteomics screens of isogenic cell lines
(±VHL) indicate that the cytosolic carbonic anhydrase isoform 2 is also target of VHL-HIF axis, but in
distinction to CA9 is repressed. Furthermore, functional studies revealed that CA2 inhibition has an
impact on renal carcinoma cells morphology and provides a protection against bicarbonate/high pH in-
duced apoptosis. These data suggest a complex response of tumor cells to the external stimuli such as
oxygen and carbon dioxide, which consequently may influence invasive and drug uptake properties.

21. Post-treatment Proximal Oesophageal Strictures in Head and Neck Cancers
N Ghazali1,2, O Noor Ullah3, RJ Shaw1,2, JM Risk1, D Lowe2, TM Jones1,4, SN Rogers2, N Kapoor3.               16
Department of Molecular & Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool. 2
1




                                                                                                                             Poster Competition
Regional Maxillofacial Unit; 3 Department of Gastroenterology; 4 Department of ENT & Head and Neck Surgery.
AINTREE UNIVERSITY HOSPITALS NHS TRUST.

Introduction: A proportion of head and neck cancer (HNC) survivors have significant swallowing dys-
function due to treatment-related oesophageal strictures (OeS). Radiotherapy-induced OeS occurs with
varying severity but is often progressive.
Study aims/objectives: To determine (i) OeS prevalence and its predictors in a large cohort and (iii)
time-to-OeS onset from treatment completion.
Method: Retrospective review of 3822 HNC patients from clinical databases (1996-September 2010)
found 65 patients with endoscopic evidence of OeS. Additional data was collected from case-notes.
Univariate and Kaplan Meier analyses were performed.
Results: Data for analysis was available in 49 patients. OeS prevalence was 17 cases per 1000 treated.
Only ‘age-at-diagnosis’ was associated with ‘time-to-OeS onset’ (p<0.03). The median ‘time-to-OeS
onset’ was 13.0 months.
Discussion/Conclusions: OeS was uncommon in a general HNC population but cause significant mor-
bidity and places high demand on healthcare service. Clinical factors including treatment were not as-
sociated with OeS onset. Current work focuses on associations of genetic polymorphisms in OeS.

22. A functional RNAi screen for DUB regulators of the PtdIns3-K pathway
Joseph J Sacco, Sylvie Urbé, Judy M Coulson and Michael Clague
Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool

Phosphatidylinositol 3-kinase (PtdIns3-K) signalling is a crucial survival pathway in multiple malig-
nancies, and an exciting target for drug development. The pathway is subject to multiple regulatory
mechanisms including ubiquitination, a process which is reversed through the action of deubiquitinat-
ing enzymes (DUBs). Our objective was to undertake a systematic investigation of DUBs involved in
PtdIns3-K signaling.
We will present data from a DUB siRNA screen in which the subcellular localization of FOXO3-EGFP
was employed as a marker of downstream activation of the PtdIns3-K pathway. Live cell imaging ena-
bled the design of a dynamic screen, in which the effects of DUB knockdown on the rate and extent of
FOXO3-EGFP translocation in response to PtdIns3-K inhibition were followed. Regulation of FOXO3-
EGFP abundance by DUBs was also assessed in this screen. Initial validation of candidates will be
presented along with exploratory findings indicating a synthetic effect between PtdIns3-K inhibition and
USP8 depletion.

23. Direct and indirect control of MAPK pathway associated components by the deubiquitylating
enzyme USP15
Han Liu, Sebastian Hayes, Ewan MacDonald, Judy Coulson, Chris Sanderson, Michael Clague,
and Sylvie Urbé
Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown street, Liver-
pool L69 3BX UK

The opposing regulators of ubiquitylation status, E3-ligases and deubiquitylases (DUBs), are often
found to be associated in complexes. Here we report on a novel interaction between the E3-ligase
BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely
related DUBs USP15 and USP4. We map the interaction to the amino-terminal DUSP-UBL domain of
USP15 and the coiled coil region of BRAP. USP15 as well as USP4 oppose the auto-ubiquitylation of
BRAP, whilst BRAP promotes the ubiquitylation of USP15. USP15 but not USP4 depletion destabilizes
BRAP yet unexpectedly results in a decrease in amplitude of MAPK signalling in response to EGF and
PDGF. We provide evidence for a model in which the dominant influence of USP15 depletion upon
signal amplitude is exerted through control of CRAF mRNA levels, whilst allowing for the possibility of
negative control by USP15 through BRAP stabilisation.

24. The tumorigenicity-promoting activity of C-FABP in prostate cancer cells depends on its fatty
acid-binding ability
Malki, M.I, Bao, Z.Z, Forootan, S, Foster, S & Ke, Y.
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA

To study the possible relationship between the tumourigencity-promoting activity of cutaneous fatty
acid binding protein (C-FABP) and its fatty acid-binding capability, mutations were generated on the
fatty acid-binding motif of the C-FABP cDNA. The wild type and mutated C-FABP cDNAs cloned into
E.Coli, to generate a clone expressing a wild type C-FABP which can bind to fatty acids; and two clones
expressing mutated C-FABPs which are less capable of binding to fatty acids. The increased wild type
C-FABP expression in Prostate cells significantly increased cell proliferation, invasiveness, and tumouri-              17
gencity in-vitro, whereas, the increased expression of both mutant forms of C-FABP did not significantly
change these characteristics. When inoculated in nude mouse, 7 out of 8 mice produced tumours in
the wild type group. In single mutant group, 4 out of 8 mice produced tumours. Whereas in the double
mutant and control group, only 3 out of 8 mice produced tumours, respectively. Our results suggest that
the biological ability of C-FABP to promote tumourigencity of the prostate cancer cells depends on its
ability of binding to fatty acids. Thus C-FABP may facilitate cancer development through transporting
fatty acids into cells.

25. Conjunctival melanoma: A multi-centre study correlating clinical information with histology
and genetics
MD thesis
Nihal Kenawy1,2, Sarah Lake1, Bertil Damato,2 Sarah Coupland1
1
     Liverpool Ocular Oncology Research Group, Molecular and Clinical Cancer Medicine, University of Liverpool
2
     Liverpool Ocular Oncology Centre, St Paul’s Eye Unit, Royal Liverpool University Hospital

Purpose: Conjunctival melanomas cause significant ocular morbidity and mortality. The treatment of this
disease is controversial, because of the lack of accurate prognostication. We aim to correlate clinical,
histological and genetic features of these tumours with disease recurrence and metastasis to determine
potential biomarkers.
Methods: Fifteen worldwide oncology centres are participating in the study. DNA will be extracted from
approximately 200 -fixed tumour samples and genetic analysis will be performed using the Affymetrix
SNP 6.0 microarray. The data will also be used to validate the current 7th edition of TNM staging sys-
tem.
Expected results: Correlation of clinical, histological and genetic data with local tumour recurrence and
metastasis should allow: 1) validation, and possibly revision, of the 7th edition of the TNM staging sys-
tem; and 2) the determination of potential biomarkers that can be used to develop an online prognostic
tool, repeating the success we have already achieved with intraocular melanoma.

26. Quantification of cellular Ras abundance
Craig J. Mageean, John R. Griffiths, Duncan L. Smith, Michael J. Clague, Ian A. Prior
Cellular and Molecular Physiology, Institute of Translational Medicine, University, Crown Street, Liverpool L69 3BX,
UK

Ras proto-oncogenes are frequently mutated in human cancers but the extent of Ras protein over-ex-
pression in cancer has not been extensively probed. Such behaviour may be important as an acquired
feature of drug resistance. Despite decades of research into Ras function, an accurate number of
molecules per cell for each Ras isoform has not so far been accomplished. Using isotopically-labelled,
full-length Ras proteins and protein standard absolute quantification (PSAQ) coupled with selective re-
action monitoring (SRM) using a triple quadrupole mass spectrometer, we measure the number of Ras
molecules per cell, discriminate between the four highly homologous isoforms: H, K(A), K(B) and N, and
provide a ratio between wild-type and mutant Ras. Our results demonstrate that Ras is a highly abun-
dant protein in cancer cell lines, as it can number over one million molecules per cell.

27. Optimization of Culture Conditions for the Analysis of the Secretome of Primary Uveal
Melanoma (UM) Cells
Martina Angi1, Rosalind Jenkins2, Bertil E. Damato3, Sarah E. Coupland1, Helen Kalirai1.
1.
  Pathology, Department of Molecular & Clinical Cancer Medicine, University of Liverpool 2. Department of Molecu-
lar and Clinical Pharmacology, University of Liverpool 3. Liverpool Ocular Oncology Centre, Royal Liverpool Univer-
sity Hospital NHS Trust, Liverpool.

Purpose: Proteins secreted by tumour cells in vitro (“secretome”) have been demonstrated to be similar
to those released by the corresponding tumours in vivo, providing a useful tool for biomarker discovery.
This study investigated the influence of culture conditions on UM secretome composition.
Methods: The secretome of primary UM cells grown in serum free medium (SFM) for 24 or 48 hours as
well as that obtained following gradual depletion of serum prior to incubation for 24 or 48 hours in SFM
were analysed using mass spectrometry. DNA was extracted from remaining UM cells for analysis by
Multiplex Ligation-dependent Probe Amplification (MLPA).
Results: Chromosomal aberrations observed in cultured UM cells were identical to those of the primary
tumour. Secretome proteins identified under the differing culture conditions were not significantly differ-
ent, and included osteopontin and secreted melanoma-associated ME20 antigen.
Conclusions: Secretome analysis could identify prognostic biomarkers of clinical relevance in UM.


                                                                                                                       18
28. Organotypic Models of Invasion Using Primary Epithelial and Mesenchymal Cells in Oral Sq-




                                                                                                                          Poster Competition
uamous Cell Carcinoma: Biological, Clinical and Translational Aspects.
Dhanda J, Risk J, Stanbury J, Woolgar J, Triantafyllou A, Shaw R, Sibson R
Department of Molecular and Clinical Cancer Medicine, University of Liverpool

Organotypic assays of invasion incorporate epithelial and mesenchymal cells in a three-dimensional
model providing opportunities to investigate the influence of underlying stroma on epithelial invasion.
Method: Primary cell culture of primary site OSCC tissue (n=40) isolated keratinocyte (n=7) and fibrob-
last (n=36) populations classified by nodal status of index tumour (N-ve, N+ECS-ve and N+ECS+ve).
After confirmation of cell phenotypes using immunofluorescence, comparisons of the pattern of invasion
(pushing, infiltrative, and non-cohesive) were made between organotypics and corresponding primary
OSCC tissue.
Results: Similarities were observed in patterns of invasion between primary tumour advancing front
and matched organotypic assays. Mesenchymal induction of invasion was seen in organotypic assays
when a non-invasive keratinocyte cell line (BHY) was combined with fibroblasts derived from metastatic
disease (ECS+ve).
Conclusions: Organotypic models using primary epithelial and mesenchymal cells have similarities to
primary tissue invasive phenotype and provide opportunities to investigate epithelial-mesenchymal
interactions with future opportunities in drug discovery.

29. Investigating the p53/MDM2 feedback loop in vivo.
Kerryanne Crawford, Nikolina Vlatković and Mark Boyd
The p53/MDM2 research group, Department of Molecular and Clinical Cancer Medicine, Institute of Translational
Medicine, The University of Liverpool, Cancer Research Centre, 200 London Road, Liverpool L3 9TA.

The TP53 tumour suppressor gene is a critical part of the damage control pathways that prevent the de-
velopment of cancer and reflecting this p53 is the most frequently mutated gene in human cancers [Vo-
gelstein, 1990]. Given the importance of p53 in human disease processes, it is not surprising that p53 is
one of the most extensively studied genes in cancer biology. However, despite considerable advances
in knowledge there are still substantial gaps in this competitive field of cancer research. Importantly it is
not yet known whether the p53-mediated up-regulation of its essential negative regulator Mdm2 is abso-
lutely required for viability. Therefore in order to address fundamental questions regarding the regulation
of p53 and Mdm2 in vivo, we proposed to generate two strains of transgenic mice which lack either the
Mdm2 P1 (constitutive) promoter or the p53 RE sites within the Mdm2 P2 (p53-responsive) promoter.
Studies of these mice are likely to have a profound impact on the field of cancer biology and normal
development.

30. Defining clathrin-TACC3 interactions in a mitotic TACC3/ch-TOG/clathrin inter-microtubule
bridge complex.
Fiona E. Hood, Samantha J. Williams & Stephen J. Royle.
Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool

Chromosome mis-segregation by the mitotic spindle is thought to drive tumour formation and propaga-
tion in cancer. Kinetochore fibres (K-fibres) are bundles of microtubules (MTs), stabilised by non-motor
inter-MT bridges, that mediate chromosome segregation. We recently identified one such inter-MT
bridge as a complex containing TACC3, ch-TOG and clathrin.
TACC3 and clathrin interact directly, which is essential for localisation of either protein to the spindle.
Localisation of TACC3 to the spindle requires its TACC domain and phosphorylation of serine 558 by
Aurora A kinase, whilst localisation of clathrin requires its N-terminal domain (NTD) and ‘ankle’ region.
We have determined which residues within these regions of clathrin heavy chain mediate direct interac-
tion with TACC3 in vitro and localisation of the complex in cells. Furthermore, we identified an extended
clathrin binding site surrounding S558 in TACC3. We show how TACC3-clathrin binding creates a pro-
tein module for mitotic spindle targeting.

31. Long term hypoxia induces etoposide resistance in Medulloblastoma.
Carol YN Fan*, Barry Pizer§, Violaine Sée*
*Institute of Integrative Biology, University of Liverpool, UK § Alder Hey Children’s NHS Foundation Trust, Liver-
pool, UK

Aim: Medulloblastoma is a malignant paediatric solid brain tumour, often deprived of oxygen (hypoxic).
Hypoxia is associated with poor prognosis and resistance to treatment. We aim to understand the effect
of hypoxia on the p53 pathway in responses to DNA damage induced by etoposide treatment. The un-
derstanding of these mechanisms will allow searches for new intracellular target for improvement of the
current therapeutic approaches.
                                                                                                                     19
Methods: Using survival assay, quantitative PCR, and ICC, we measured the cell sensitivity to etopo-
side and the associated p53 activation in normoxic or hypoxic conditions. We also assessed the role
and dynamics of hypoxia-inducible factor (HIF) during long-term hypoxia by western blotting.
Results: We have demonstrated that medulloblastoma cells become more resistant to etoposide in
chronic hypoxia correlated with a reduced DNA damage response to etoposide. We saw a reduced
etoposide-induced H2AX phosphorylation, p53 phosphorylation and loss of p53 transcriptional activity
in chronic hypoxic cells.

32. Imaging the impact of hypoxia on neuroblastoma behaviour in live chick embryos
Anne Herrmann1, 2, Raphaёl Lévy3, Barry L. Pizer4, Paul D. Losty5, Diana Moss2 and Violaine Sée1
1
 University of Liverpool, Centre for Cell Imaging, UK; 2University of Liverpool, Cellular and Molecular Physiology,
UK 3University of Liverpool, Structural and Chemical Biology, UK 4Paediatric Oncology, Alder Hey Children’s NHS
Foundation Trust, UK 5Academic Paediatric Surgery Unit, Division of Child Health, University of Liverpool, UK

Hypoxia occurs in solid tumours such as neuroblastoma and may promote reprogramming of neuroblas-
toma cells leading to the emergence of an ‘aggressive’ stem cell phenotype able to evade chemothera-
py and resulting in poor clinical prognosis. We investigated the role of the oxygen microenvironment on
the dedifferentiation and aggressiveness of neuroblastoma cells in vivo. Most in vivo findings are based
on histological methods, end point measurements and fixed samples failing to address the spatiotem-
poral behaviour of tumour cells in patients. To study the influence of hypoxia on neuroblastoma invasion
and migration over time we utilise the avian model permitting real-time visualisation of cellular dynamic
events in the entire living organism.
Neuroblastoma cells were labelled with fluorescent proteins and grown as adherent cells or tumour
spheres under normoxia or hypoxia. Cell proliferation, stem cell and differentiation markers were ana-
lysed by immunocytochemistry, histological methods and live whole embryo imaging. To monitor the
dynamic events of neuroblastoma cells and their ability to invade tissues and form tumours, single-cell
suspensions were injected into chick embryos and imaged with a custom-built high-resolution fluores-
cent microscope.
We have shown that hypoxia (1 % O2) causes neuroblastoma cells to form tumour-like structures when
compared with co-injected cells grown in normoxia. These differences could be observed shortly after
injection and persisted during embryonic development.
The ability to study the impact of hypoxia on neuroblastoma cell dynamics in live intact embryos using
high-resolution imaging is an important step toward understanding neuroblastoma behaviour and the
molecular mechanisms underlying its aggressiveness and unpredictable clinical behaviour.

33. Role of miR-181-d and Wnt signalling in gastric cancer-associated myofibroblasts
Liyi Wang1, Islay Steele1, Rod Dimaline1, Graham Dockray1, Andrea Varro1,2
Departments of Cellular and Molecular Physiology1, and Molecular and Clinical Cancer Medicine2, Institute of
Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

MicroRNAs (miRNAs) are regulators of gene expression and are deregulated in stromal cells such as
myofibroblasts. A previous array study identified differential miRNA expression in gastric cancer-asso-
ciated myofibroblasts (CAMs) compared to their adjacent counterparts, and network analysis revealed
that differentially expressed miRNAs were implicated in Wnt signalling. We have now evaluated one of
the differentially regulated miRNAs, hsa-miR-181d. Increased hsa-miR-181d in CAMs was confirmed
by qPCR; Western blot and qPCR confirmed increased Wnt-5a in CAMs. Addition of Wnt-5a increased
hsa-miR-181d in CAMs, and stimulated CAM migration and proliferation. CAM-conditioned media
(CAM-CM) stimulated cancer cell migration; hsa-miR-181d knockdown inhibited, and over-expression
increased CAM-CM stimulated cancer cell migration. Inhibition of expression of the matrix metallopro-
teinase inhibitor, TIMP-3, by hsa-miR-181d, was identified as a functionally relevant target. Thus, Wnt-
stimulated hsa-miR-181d expression in CAMs leads to stimulation of cancer cell migration via modula-
tion of TIMP-3 expression.

34. Proteolytic remodelling of the secretome in gastric cancer-associated myofibroblasts
Holmberg C,1 Cash N,1 Gevaert K,3,4 Ghesquière B,3,4 Impens F,3,4 Kumar D,1 Dockray GJ,1 Varro
A1,2
Departments of Cellular and Molecular Physiology1, and Molecular and Clinical Cancer Medicine2, Institute of
Translational Medicine, University of Liverpool, 3Department of Medical Protein Research, VIB, Ghent, Belgium and
4
  Department of Biochemistry, Ghent University, Ghent, Belgium

Changes in the cellular microenvironment characterise cancer progression. The role of stromal cells
in these changes is increasingly recognised but little is known of stromal cell secretomes or how they
might change with cancer progression. To identify tumour-specific proteolytic cleavages in the secre-
tomes of gastric cancer-associated myofibroblasts (CAMs) we applied the technique of N-terminal
Combined FRActional DIagonal Chromatography (COFRADIC) to CAM media compared to media of
myofibroblasts from adjacent tissue (ATMs). Neo-N-termini identified in CAM media included the acti-                  20
vated forms of matrix metalloproteinases (MMP)-1, -2 and -3. Western Blot confirmed the presence of the




                                                                                                                               Poster Competition
active forms of these enzymes in CAM but not ATM media. MMP-1, -2 and -3 stimulated cancer cell migra-
tion, and their selective inhibition decreased cancer cell migration in response to CAM-conditioned media.
Thus, stromal cell secretomes contribute to remodelling of the tumour microenvironment by activation of
MMPs thereby facilitating cancer cell migration.

35. Chemerin is a bone marrow stromal cell chemoattractant released by myofibroblasts in squa-
mous tumours of the oesophagus
Kumar JD1, Holmberg C1, Steele I1, Dockray GJ1, Varro A1,2
1
 Departments of Cellular and Molecular Physiology, and 2Molecular and Clinical Cancer Medicine, University of Liver-
pool, Liverpool, UK

Bone marrow-derived mesenchymal stromal cells (MSCs) colonize tumours and following differentiation
can accelerate cancer progression. The mechanisms are unclear. Using proteomic methods we identi-
fied the adipokine, chemerin, as overexpressed in myofibroblasts from oesophageal squamous cancers
(CAMs) compared with adjacent tissue myofibroblasts (ATMs). We hypothesised that chemerin might
act as an MSC chemoattractant. Immunocytochemistry showed expression of the chemerin receptor
(ChemR23) in MSCs. CAM conditioned media (CM) significantly increased MSC migration compared with
ATM-CM. The migratory response was reduced after treatment of CM with chemerin- neutralising anti-
body, or pretreatment of CAMs with chemerin siRNA, while CAM-CM following chermin overexpression
enhanced MSC migration. Recombinant chemerin increased phosphorylation of p42/44, p38 and JNK-II
kinases in MSCs and inhibitors of these kinases and PKC reversed chemerin-stimulated MSC migration.
ChemR23 knockdown in MSCs inhibited both chemerin and CAM-CM stimulated MSC migration. Thus,
chemerin secreted from cancer myofibroblasts may recruit MSCs to oesophageal squamous tumours.

36. Identification of regulators of metastasis in uveal melanoma
Sarah L. Lake1, Bertil E. Damato2, Azzam F.G. Taktak3, Bryony H. Lloyd4, Lisa Olohan5, Xuan Liu5
and Sarah E. Coupland1
1
 Liverpool Ocular Oncology Research Group, Dept. of Molecular & Clinical Cancer Medicine, University of Liverpool;
2
 Liverpool Ocular Oncology Service, Royal Liverpool University Hospital; 3Department of Medical Physics and Clinical
Engineering, Royal Liverpool University Hospital; 4Applied Cancer Biology, Dept. of Molecular & Clinical Cancer Medi-
cine, University of Liverpool; 5Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool.

Background: Uveal melanomas can be accurately stratified into subgroups with high- or low-risk of meta-
static death according to clinical and histomorphological features, and gross chromosomal abnormalities.
Despite this, the genes driving metastasis are not well defined.
Purpose: To identify genetic drivers of uveal melanoma metastasis.
Materials and methods: Well-characterised uveal melanoma specimens were analysed by whole-genome
microarray (Affymetrix SNP 6.0 array; n=58) and whole-exome sequencing (n=12). Systems biology al-
lowed prioritisation of genes in cell signalling pathways associated with metastasis for further investigation
(Metacore). Cox regression and Kaplan-Meier survival analysis identified genes that were associated with
patient survival.
Results:Patients with an amplification of CNKSR3 (6q) or RIPK1 (6p) had longer survival than those
without an amplification (logrank, p=0.022 and p<0.001, respectively). Conversely, those patients with an
amplification of PENK (8q) showed reduced survival (logrank p<0.001).
Conclusion: CNKSR3, RIPK1 and PENK are novel candidate metastasis-regulatory genes in uveal
melanoma.
37. Effect of Myofibroblasts on Long-Range Signalling in Gastric Cancer
S. Kandola, G. Dockray, A. Varro
Department of Cellular and Molecular Physiology, University of Liverpool

Epithelial cancers consist of cancer cells and stromal cells including myofibroblasts that locally stimulate
cell proliferation and invasion. Tumours also send long-range signals influencing distant sites including
bone marrow and other tumours, but the role of myofibroblasts in this is poorly understood. We hypoth-
esised that gastric cancer-associated myofibroblasts (CAMs) generate long-range signals that affect
distant tumour growth. To address this, bilateral xenografts were established by subcutaneous injection
of MKN45 cells with or without CAMs in nude mice. Co-administration of CAMs with MKN45 cells (n=11)
enhanced local tumour volumes 2-fold compared with bilateral MKN45 controls (123±51 vs 228±46 mm3).
However, xenografts composed of CAMs and MKN45 cells suppressed the growth of distant xenografts
containing MKN45 cells alone (123±51 vs 32±10 mm3, p=0.03). Previous work identified TGFβig-h3 as
a putative long-range tumour suppressor; the present studies will enable us to dissect the mechanisms
involved and to evaluate therapies to inhibit distant metastasis.


                                                                                                                          21
38. The deubiquitylase USP15 stabilises newly synthesised REST during the cell cycle.
Monica Faronato, Laura Dearden, Sarah Darling, Sebastian Hayes, Sylvie Urbé and Judy M
Coulson
Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown St, Liver-
pool, L69 3BX, UK

REST (RE1-silencing transcription factor) is a transcriptional repressor that regulates neurogenesis
and acts as a context-dependent tumour suppressor or oncoprotein1. It is polyubiquitylated and
degraded during neuronal differentiation and cell cycle progression2-3. Deubiquitylases (DUBs) re-
move ubiquitin from substrates4, and we screened for DUBs that were capable of stabilising REST
in lung cancer cells. REST protein levels were specifically reduced by USP15 depletion, and this
was reversed by proteasome inhibition. USP15 (but not the catalytically inactive mutant) deubiq-
uitylated REST and rescued endogenous REST levels. USP15 did not antagonise the degradation
of phosphorylated REST at mitosis, but importantly supported the rapid re-accumulation of REST
on mitotic exit. Similarly, in asynchronous cells USP15 depletion did not destabilise pre-existing
REST, but rather impaired ‘de novo’ REST synthesis on removal of a cycloheximide block. Thus
cellular oscillations in REST abundance depend in part on deubiquitylation by USP15, which is
primarily directed towards newly synthesised REST.
References: 1 Coulson, Current Biology 2005; 15:R665-8 2 Westbrook et al, Nature 2008; 452:370-4 3 Guarda-
vaccaro et al, Nature 2008; 452:365-9 4 Clague et al, JCS 2012; 124:277-86

39. Fast removal of inter-microtubule bridges reveals new roles in mitotic spindle assembly
and function
L. P. Cheeseman, I. A. Prior and S. J. Royle
Department of Molecular and Cellular Physiology, Nuffield Building, Crown Street, University of Liverpool,
Liverpool L69 3BX, UK

Kinetochore fibre (K-fibre) stability is critical to mitotic spindle function. TACC3/ch-TOG/clathrin
complexes crosslink K-fibre microtubules and contribute to efficient mitosis. Here, we determined
the function of crosslinkers in mature K-fibres versus their role in K-fibre formation. “Knock-side-
ways” was used to rapidly and specifically remove the complex from the spindle (~5 min) at defined
stages of mitosis. Knock-sideways after prophase caused severe delays in chromosome alignment,
similar to TACC3 RNAi. Removal of crosslinkers at metaphase (following normal prometaphase)
significantly delayed progression to anaphase. In these cells, K-fibre tension was relaxed and the
spindle checkpoint active. Surprisingly, when we analysed K-fibre ultrastructure by correlative
light-electron microscopy, we found no significant loss of K-fibre microtubules even after prolonged
bridge removal. This suggests that tension is important for silencing the spindle checkpoint inde-
pendently of microtubule number. Our results indicate that TACC3/ch-TOG/clathrin crosslinkers are
important for both the formation and function of K-fibres.

40. Core Outcomes in Late Phase Head and Neck Cancer Clinical Trials
Aoife Waters1, Prof TM Jones1, Dr C Tudur-Smith2, Prof B Young3
1
 Liverpool CR-UK Centre, Department of Molecular and Clinical Cancer Medicine 2Department of Biostatis-
tics, Faculty of Health & Life Sciences, University of Liverpool 3Department of Mental and Behavioural Health
Sciences, Institute of Psychology, Health and Society, University of Liverpool

A core outcome set (COS) represents the minimum that should be measured and reported in all
clinical trials of a specific condition. These aim to reduce problems of heterogeneity and outcome
reporting bias, and improve the contribution of trial data for meta-analyses.
Core outcome measures, whether surrogate, functional, quality of life or survival related, do not
exist for Head and Neck Cancer (SCCHN) clinical trials, making it particularly difficult to identify
optimal treatment regimens when comparing data from competing trials.
A systematic review of the literature will identify the outcomes reported in SCCHN clinical trials. Cli-
nician focus groups and patient and carer semi-structured interviews will be conducted. Consensus
exercises, involving clinicians, patients and carers, will determine which outcomes are important to
stakeholders and should therefore be included in the COS for use in OPSCC clinical trials.

41. Hydration status in advanced cancer patients: assessment of a novel evaluation tech-
nique
Dr Amara C Nwosu1, Dr Catriona R Mayland1,2, Dr Evelyn MI Williams3, Dr Stephen Mason1,
Professor John E Ellershaw1
Marie Curie Palliative Care Institute Liverpool (MCPCIL), University of Liverpool 2Aintree University Hospital
1

NHS Foundation Trust 3School of Public Health, University of Liverpool

Background: There is limited scientific understanding of (de)hydration in advanced cancer. Con-
sequently, decisions surrounding the administration of clinically assisted hydration (CAH) to dying               22
cancer patients are challenging. Bioelectrical impedance analysis (BIA) has shown promise in assessing




                                                                                                                             Poster Competition
(de)hydration.
Aim: To critically appraise existing methods of hydration status assessment and review the potential for BIA
to assess (de)hydration in advanced cancer patients.
Methods: Systematically structured review of literature.
Results: Eleven articles were identified. Clinical examination and biochemical tests are standard methods
of assessing (de)hydration; however, limitations exist with these in advanced cancer. There is disagreement
over the evidence for commonly associated dehydration symptoms in cancer. BIA may have a role in evalu-
ating (de)hydration, but no studies of cancer patients have been conducted.
Conclusions: Innovative research methodologies using BIA, combined with regression analyses of biochemi-
cal and symptom indications, may potentially improve scientific knowledge of (de)hydration and patient care.

42. Human Papillomavirus (HPV) associated Head and Neck Squamous Cell Carcinoma (SCC) arising
in sites other than the Oropharynx.
N. Upile, M. Robinson, P. Sloan, A. Schache, P. Goodyear, J. Sheard, M.T. Boyd & T. M. Jones.
p53/MDM2 group, Cancer Research Centre, 200 London Road, Liverpool L3 9TA and Department of Otorhinolaryngol-
ogy & Head and Neck, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool L69 3GA

Background: There is a paucity of data regarding HPV-association in
carcinomas arising from the other (non-oropharynx) subsites of the upper
aerodigestive tract.
Aim: To establish the HPV-rates in Laryngeal and Hypopharyngeal SCCs.
Methods: We employed a diagnostic algorithm using p16 Immuno-Histo-
chemistry (IHC), Chromogenic-In-Situ-Hybridasation (CISH) and Real-
Time (RT) PCR to detect the presence of HPV-DNA (See Figure 1).This is
the
effective gold standard when RNA is not available from archival fresh
frozen paraffin embedded samples. Staining of all samples were reported
independently by two pathologists.
Results: The overall HPV positive-status of our larynx cohort was
3/91(3%). The overall HPV positive-status of our Hypopharynx cohort was
2/28(7%).
Discussion: Whilst low, HPV-driven cancer is not a rare event outside the
oropharynx. The incidence of laryngeal cancer in the USA is estimated at
                                                                           Figure 1 Diagnostic Algorithm
12,740 for 2011 – amounting to a burden of 400 new cases of HPV+ve
larynx SCC assuming our data can be extrapolated. It is now recognised employed
that the survival of HPV+ve OPSCCs is better than its HPV-ve counterpart and may warrant a stratified ap-
proach to treatment. It may be that similar consideration needs to be made for SCCHNs arising from sites
other than the oropharynx.

43. Reactivating Wild Type p53 in Renal Cell Carcinoma Cells to induce Apoptosis: A Combinatorial
Approach
Amro Ahmed-Ebbiary, Radoslaw Połański, Mike Thornton, Nikolina Vlatković and Mark T. Boyd
p53/MDM2 Group, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University
of Liverpool , Cancer Research Centre 200 London Road, Liverpool L3 9TA,

BACKGROUND: Renal cell carcinoma (RCC) is the 8th commonest cancer in the UK and the incidence has
doubled in the last 30 years. Curiously, p53 is rarely mutated in RCC, but up-regulation of wild-type p53,
together with Mdm2, is an independent prognostic indicator linked with reduced survival in RCC 1. In RCC
cells harbouring wild type p53 we have found that p53 is substantially regulated by Mdm2, but rescue of p53
by inhibitors of the Mdm2/p53 interaction fail to induce apoptosis.
AIMS: To rationally identify means to activate p53-mediated apoptosis in RCC cells?
METHODS: A panel of RCC cell lines harbouring both wild-type and mutant p53 were treated with MDM2
inhibitor Nutlin-3 and BH-3 mimetic Abt-737. Survival and apoptosis assays were performed and data ana-
lysed by isobolar plots.
CONCLUSIONS: Nutlin-3 and Abt-737 synergistically induce apoptosis in RCC cells harbouring wild-type
p53. This effect is p53-dependent, being abrogated by p53 shRNA. This combination of drugs has no effect
on non-transformed immortalised renal cells, suggesting a high therapeutic index may be achievable. This
drug combination warrants further investigation in pre-clinical and clinical settings due to the retention of
wild-type p53 in this disease. 1. Noon AP, Polanski R, El-Fert AY, et al. BJU Int 2011.
                                                                                                                        23
44. Characterisation of the effect on the growth characteristics of pancreatic cell lines of knocking
down K-Ras using siRNA
Robert Ferguson, Eithne Costello, John P Neoptolemos and William Greenhalf
Department of Molecular and Clinical Cancer Medicine, Institute of Translatinal Medicine, University of Liv-
erpool.
Introduction: K-Ras mutations occur in 75-90% of pancreatic adenocarcinomas. Because K-Ras acts up-
stream of a complex network of pathways it is difficult to know what effects these mutations have, particu-
larly given the variety of genetic backgrounds cancer cells will generate. We are particularly interested in the
Kennedy pathway which lies downstream of both K-Ras and PI3K. Modification of this pathway will change
the membrane lipid component of the cell; thus affecting uptake of drugs and many other cellular features.
Decreasing levels of K-Ras protein in pancreatic cell lines has been reported to cause a decrease in growth
and an increase in cell death via apoptosis. The aim of this work initially is to determine the effect of K-Ras
knock down on four pancreatic cell lines MiaPaCa2, PANC-1 and Suit-2 (which have mutant KRAS2) and
BxPC3 (wild type KRAS2). Once this has been determined we will look at the membrane lipid composition
of the cells to see what effect if any K-Ras has on the lipids present in the membrane with and without PI3K
inhibition.
Methods: BxPC3, MiaPaCa2, PANC-1 and Suit-2 cell lines have had K-Ras knocked down and their growth
characteristics were determined using FACS. The cells were analysed to determine the changes relevant to
the levels of KRAS in the Suit-2 cell line.
Results/Conclusion: Knock down was optimised using a pool of SiRNA, effects on growth varied in different
cell lines. All cell line survived at least 72hrs post knockdown. FACS analysis indicates that the cells arrest
in G1. Cells begin to grow again once levels of K-Ras begin to increase, before normal levels are achieved.
Experiments are ongoing looking at the membrane lipid profile of these cells.

45. Genetic screening to identify enzymes affecting the spread of ovarian cancer.
Neville Cobbe, Sarah Forrester, Jenny Horend, Hussain Jaffery, Sally Quine, Amy Rothwell, Shaun
Speldewinde, Sarah Taylor, Adriana Guillermo Wiesinger, Helen Young and Daimark Bennett
Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK

Ovarian cancer is an aggressive form of carcinoma that is regrettably difficult to detect before metastasis,
rendering treatment very difficult. Our goal is to understand the cause and mechanisms of this invasive
cell migration by using the fruit fly, Drosophila melanogaster. During normal development of the Drosophila
ovary, a specialized group of epithelial cells (known as the border cell-cluster) migrates through the egg
chamber in a manner akin to the invasive migration of ovarian cancer cells. As border cell migration can be
readily visualized microscopically, this provides a powerful model system to study the mechanics of ovarian
cancer metastasis in vivo, with conserved genes previously implicated in both processes alike. Our major
focus is on the way cancers are controlled by reversible phosphorylation, by identifying kinases and phos-
phatases affecting border cell migration. We have compiled an extensive database of conserved Drosophila
kinases and phosphatases, using this to design genetic crosses in which a short hairpin RNA (shRNA) could
be specifically produced under the control of the GAL4 transcription factor expressed ectopically within bor-
der cells, ideally leading to depletion of a particular enzyme within the border cells by means of RNA inter-
ference (RNAi). Here we will present and discuss the results of two successive genetic screens performed
blindly with UAS-shRNA lines from different sources, which have been retrospectively validated by identifi-
cation of enzymes independently characterized as important for border cell migration.

46. BAP1 protein expression in uveal melanoma (UM); high throughput analysis using tissue micro-
arrays (TMA) of primary uveal melanoma (PUM) and liver metastases (MUM).
Helen Kalirai1, Andrew Dodson1, Sohaib Faqir1, Bertil Damato2 and Sarah Coupland1
Pathology, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK 2 Liverpool
1

Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK

Purpose: Inactivating mutations of the deubiquitinating enzyme BRCA1 associated protein 1 (BAP1; chro-
mosome 3p21.1) occur in 84% of poor prognosis UM. We correlated BAP1 protein expression in TMAs of
primary and metastatic UM with histological and clinical data and with survival.
Methods: BAP1 protein expression was assessed by immunohistochemistry in TMAs of PUM (1) and MUM
(2). The percentage of tumour cell nuclei staining positively was scored blind by three independent asses-
sors. Statistical analyses were performed in SPSS.
Results: BAP1 protein was either completely absent or present in >75% tumour cell nuclei in each TMA
core. In TMA1, absence of BAP1 protein correlated significantly with histological features of poor prognosis.
Patients were more likely to die from metastatic melanoma if BAP1 protein was absent. BAP1 protein was
absent in 89% of MUM cases. Expression was 100% concordant in paired cases of PUM and MUM.
Conclusion: Absence of the tumour suppressor BAP1 correlates with metastasis of UM.
                                                                                                                      24
               Congratulations to last year’s winners




                                                                                                    2011 Winners
     Liam Cheeseman (best short talk) and Victoria Shaw (best poster).




Liam and Victoria pictured above, each receiving their £300 travel award from Steve Jackson.




                                                                                               25
 Liverpool Cancer
Research UK Centre
     2011-12


Since last year’s Annual Meeting, the Liverpool Cancer Research UK Centre has
been honoured with the Freedom of the City of Liverpool.

Researchers from the Centre have been engaged through CRUK LEAD in many
activities ranging from school and MP visits to Race for Life, Black History Month
HeLa event, and Liverpool Pride.

Guest speakers welcomed to the Centre this year include; Professor Michael Rape,
Berkeley, CA; Professor Paul Clarke, Dundee; Dr Miguel Martins, Leicester; Dr Adrian
Saurin, Utrecht; Dr Michael von Bergwelt-Baildon, Cologne; Dr Stephan Feller,
Oxford; Dr Laura Pasqualucci, Coumbia, NY; Professor Marco Falasca, Barts;
Professor Carsten Denkert, Berlin; Dr Elad Katz, Edinburgh; and Professor Alfred
Goldberg, Harvard University.
     Freedom of the City




Wednesday 8th February 2012 was a momentous day for Liverpool Cancer Research UK Centre,
with over 160 guests attending a special event at Liverpool Town Hall to celebrate the presen-
tation of our Scroll of Admission to the City’s Freedom Roll of Associations and Institutions.
The award was given in recognition of the Centre’s groundbreaking research, it’s Centre of
Excellence status, and our cancer awareness outreach work with local people.

The evening began with a buffet reception; guests were welcomed by the Lord Mayor,
Professor and Mrs. Neoptolemos, and Dr. Harpal Kumar, Chief Executive of Cancer Research UK.

Guests included doctors, nurses and scientists from the Centre, civic dignitaries, representatives
of Liverpool and Everton Football clubs, cancer survivors, and supporters. Model, ECHO
columnist and friend-of-the-Centre Amanda Harrington also attended.

The Lord Mayor of Liverpool, Councillor Frank Prendergast presided over the ceremony, which
took place in the Council Chamber. Testimonies were given by Dr. Kumar, Professor Sir Howard
Newby (University of Liverpool) Andrew Cannell (The Clatterbridge Cancer Centre), Derek
                                                                                                          Liverpool CRUK Centre




Campbell (NHS Merseyside), Jon Hayes (Merseyside and Cheshire Cancer Network), Tony Bell
(Royal Liverpool University Hospital), patient representatives Dennis Helsby and Bernie
Singleton, and Professors Dan Palmer and Paula Ghaneh spoke about the future plans for the
Centre. A choir of cancer survivors from Sunflowers Cancer Support Centre, based on Aigburth
Road, sang, “Here Comes the Sun”.

Following presentation of the Freedom Scroll and the signing of the register, Professor
Neoptolemos presented the Centre’s Pledge to the City, to fight cancer through research,
train cancer professionals of the future, and through working with local people to help them
understand, avoid, and overcome cancer.
                                                                                                     27
      In the past 12 months...
Bioinformatics Workshop
The Centre held a Bioinformatics workshop
highlighting the excellent statistics and
bioinformatics support available to all members of
the Centre. The workshop was well-attended and
colleagues heard from the Bioinformatics Team on
Sequence Analysis, Systems Biology, Cross Platform
Technologies for Biomarkers, Microarray Analysis,
and Statistical Aspects of Bioinformatics.

Trial Showcase at NCRI Conference
Professor Andrew Pettitt was selected to present in the Clinical Trials Showcase at the 2011
NCRI Cancer Conference for his abstract entitled: Alemtuzumab in combination with methylpred-
nisolone is a highly effective induction regimen for patients with chronic lymphocytic leukaemia
and deletion of TP53: Final results of the National Cancer Research Institute (NCRI) CLL206 Trial.

                                            Race for Life Challenge!
                                            Charlotte Rawcliffe (Liverpool Cancer Trials Unit)
                                            completed ten Race for Life events last summer.
                                            Charlotte ran the last Race at Knowsley accompa-
                                            nied by other members of staff from LCTU.
                                            Charlotte raised over £1,000 for CRUK.




PBRU Research nurses complete the
Sandstone Trail
The team of research nurses from the Royal
Liverpool University Hospital completed a 55km
walk to raise awareness of the Pancreatic
Biomedical Research Unit at Liverpool; the team
raised over £1,500 for CRUK.




                                           Liverpool Pride
                                           Researchers from Liverpool Cancer Research UK
                                           Centre supported Liverpool Pride last year, taking
                                           part in the march through Liverpool City Centre
                                           meeting friend-of-the-Centre, Stephen Twigg MP,
                                           along the way.


                                                                                                     28
UK Young Scientist of the Year award for Centre’s Young Researcher




                                                                                                       Centre Activity
                    Kirtana Vallabhaneni, 17, from West Kirby won the UK Young Scientist of
                    the Year Award in recognition of a Summer project carried out in Dr Eithne
                    Costello’s lab. She was awarded the prize at the Big Bang Fair in
                    Birmingham in March. Kirtana intends to study Medicine at UCL.

                     Children’s University Day
                     The Centre held it’s first Children’s University Open Day last November,
                     with families from local schools visiting cancer awareness stalls and
                     spending time with our scientists in the labs. The children also took away
                     information about how to support the charity through volunteering and
collected funds for CRUK on toy and book stalls.

Ocular Oncology Team shortlisted for Pfizer Excellence in Oncology
The Liverpool Ocular Oncology Centre/Liverpool Ocular Oncology Research Group were
                                         exceedingly pleased to be one of three short-listed
                                         entrants for the Pfizer Excellence in
                                         Oncology: Oncology Team of the Year Award, 2011.
                                         The work of the team was commended by the
                                         judges.

                                           The Oncology Team of the Year is described as
                                           recognising a demonstration of outstanding
                                           teamwork in any area within oncology education,
                                           management, and patient care.


Model, Amanda Harrington visited the Centre
Liverpool model and ECHO columnist, Amanda
Harrington visited the Centre to learn about cancer
research in the city. Amanda took part in the
Knowsley Race For Life and urged women to return
their sponsorship cash as she spoke to researchers.
She said: “Taking part in Race For Life was
enormous fun, but thousands of women taking part
in events all over Merseyside were also making a big
difference to the work of Cancer Research UK.
“The money raised by Race For Life is vital to helping fund the research which will make a
difference to future generations affected by cancer.”


Pyrosequencing Training Course
Pyrosequencing is a widely used technique in cancer
research; in particular, the analysis of genetic and
epigenetic changes of cancer cells. The first (taught) part
of the course covered the chemistry and workflow of the
method as well as details on assay design, participants
then designed their own assays in breakout groups with
the assistance of Dr Lakis Liloglou and his group. This was
the first of a series of methodology workshops planned,
which in addition to the weekly Liverpool CRUK Centre seminars, aim to keep our research-
ers updated in the latest cutting edge knowledge and technology used in cancer research.
                                                                                                  29
Attendees List                                      Chen, Jack: cheny@liverpool.ac.uk
                                                    Clague, Michael: clague@liverpool.ac.uk
                                                    Clarke, Christopher: cjclarke@liverpool.ac.uk
Abdalla, Samir: md0u9339@liverpool.ac.uk
                                                    Cobbe, Neville: ncobbe@liverpool.ac.uk Poster 45
Abu-Alainin, Wafa: wafamahd@liverpool.ac.uk
                                                    Costello, Eithne: ecostell@liverpool.ac.uk
Acha-Sagredo, Amelia:
                                                    Coulson, Judy: jcoulson@liverpool.ac.uk
ameachas@liverpool.ac.uk
                                                    Coupland, Sarah: amelie@liverpool.ac.uk
Ahmed-Ebbiary, Amro:
                                                    Crawford, Kerryanne: kez@liverpool.ac.uk Poster 29
ahmedebb@liverpool.ac.uk Poster 43
                                                    Cross, Michael: mjcross@liverpool.ac.uk
Al-Khafaji, Ahmed: hamdmad@liverpool.ac.uk
                                                    Darling, Sarah: ph0u8066@liverpool.ac.uk
Al-Sanabra, Ola: ola81@liverpool.ac.uk
                                                    Davies, Michael: mpdavies@liverpool.ac.uk
Allen, John: jcallen@liverpool.ac.uk
                                                    Dhanda, Jag: jdhanda@liverpool.ac.uk Poster 28
Algahanem, Ahmad: asn740@liverpool.ac.uk
                                                    Dodgson, Lauren: ph0u6047@liverpool.ac.uk
Alqadri, Nada: nadaali@liverpool.ac.uk
                                                    Poster 19
Angi, Martina: mangi@liverpool.ac.uk Poster 27
                                                    Dodson, Andrew: dodson@liverpool.ac.uk Poster 11
Anvari Azar, Ali: alixan@liverpool.ac.uk
                                                    Du, Min: siyu@liverpool.ac.uk
Bardelli, Alberto: alberto.bardelli@ircc.it
                                                    Duckworth, Carrie: carried@liverpool.ac.uk
Guest Speaker
                                                    Eagle, Gina: gleagle@liverpool.ac.uk
Baron, Ryan: barorya@liverpool.ac.uk Poster 4,
                                                    Ellershaw, John: johne61@liverpool.ac.uk
Short Talk Speaker
                                                    Elliott, Victoria: velliott@liverpool.ac.uk
Barsukov, Igor: I.Barsukov@liverpool.ac.uk
                                                    Elmitwalli, Taha: elmetwaa@liverpool.ac.uk
Baudo, Marcela: marcelab@liverpool.ac.uk
                                                    Emmett, Maxine: msemmett@liverpool.ac.uk
Poster 15
                                                    Evans, Anthony: aevans@liverpool.ac.uk
Beardshaw, Catherine: catherine.beardshaw@
                                                    Fan, Carol: carolfan@liverpool.ac.uk Poster 31
aintree.nhs.uk CEO, University Hospital Aintree
                                                    Farahani, Mosavar: mosavar@liverpool.ac.uk
Beckett, Alison: alib@liverpool.ac.uk
                                                    Faronato, Monica: faronato@liverpool.ac.uk Poster 38
Bee, Alix: bee@liverpool.ac.uk
                                                    Ferguson, Robert: rf1@liverpool.ac.uk Poster 44
Bennett, Daimark: daimark@liverpool.ac.uk
                                                    Field, John: jkf51@liverpool.ac.uk
Blocksidge, Jemma: jemmab@liverpool.ac.uk
                                                    Fielding, Andrew: andrewf@liverpool.ac.uk
Boyd, Mark: mboyd@liverpool.ac.uk
                                                    Garner, Liz: egarner@liverpool.ac.uk
Bullock, Katie: katieb81@liverpool.ac.uk
                                                    Ghazali, Naseem: nazghaz@liverpool.ac.uk Poster 21
Campbell, Barry: bjcampbl@liverpool.ac.uk
                                                    Giger, Olivier: gol@liverpool.ac.uk
Cannell, Andrew: andrew.cannell@ccotrust.nhs.
                                                    Goss, Mel: gossm1@liverpool.ac.uk
uk CEO, The Clatterbridge Cancer Centre
                                                    Graham, Sean: sean.graham@novartis.com, Novartis
Carter, Rachel: rachel86@liverpool.ac.uk Poster 3
                                                    Greenhalf, Bill: greenhaf@liverpool.ac.uk
Cash, Nicole: cashn@liverpool.ac.uk Poster 34
                                                    Greenwood, Geoff: geoff.greenwood@ccrmail.org
Chang, Shie Hong: shc2010@liverpool.ac.uk
                                                    Chairman, Clatterbridge Cancer Research
Poster 1
                                                    Greer, Ian: iag@liverpool.ac.uk
Chapman, Elinor: echapman@liverpool.ac.uk
                                                    Hammond, Dean: becks11@liverpool.ac.uk
Cheeseman, Liam: lpc09@liverpool.ac.uk
                                                    Short Talk Speaker
Poster 39
                                                    Harrold, Jane: jlh7@liverpool.ac.uk
Chen, Chen: chendd@liverpool.ac.uk
                                                    Hayes, Jon: jon.hayes@mccn.nhs.uk Deputy Director,
Chen, Danqing: nsc2007@liverpool.ac.uk
                                                    Merseyside and Cheshire Cancer Network                 30
Heride, Claire: cheride@liverpool.ac.uk Poster 8     Redx Oncology, Managing Director
Hernandez-Valladares, Maria:                         Linnane, Emily: eelin1@liverpool.ac.uk
mariahv@liverpool.ac.uk                              Liu, Han: liuhan@liverpool.a.cuk Poster 23
Herrmann, Anne: herrmann@liverpool.ac.uk             Losty, Paul: pdlsty21@liverpool.ac.uk
Poster 32                                            Lucy, John: john.lucy@liverpoolpct.nhs.uk
Heyward, Catherine: cheyward@liverpool.ac.uk         Associate Director of Public Health
Poster 13                                            Lyons, Suzanne: bs0u4070@liverpool.ac.uk
Higgins, Rebekah: rhiggins@liverpool.ac.uk           Macdonald, Ewan: ewanmac@liverpool.ac.uk Poster 10
Hill, Iain: hilli@liverpool.ac.uk                    Mageean, Craig: mageean@liverpool.ac.uk Poster 26
Holcombe, Chris: chris.holcombe@rlbuht.nhs.uk        Malec, Viktor: viktorm@liverpool.ac.uk Poster 20
Lead Cancer Clinician, Royal Liverpool               Malki, Mohammed: emad200@liverpool.ac.uk Poster 24
University Hospitals                                 Marais, Richard: rmarais@picr.man.ac.uk
Hood, Fiona: fehood@liverpool.ac.uk Poster 30        Guest Speaker
Hussain, Syed: hussaisa@liverpool.ac.uk Speaker Marcus, Michael: marcusmw@liverpool.ac.uk
Hyde, Russell: arhyde@liverpool.ac.uk                Mason, Stephen: maceo@liverpool.ac.uk
Ismail, Thamir: tismail@liverpool.ac.uk              Mcevoy, Ian: ian.mcevoy@sial.com, Sigma
Jenkins, John: john.jenkins@liverpool.ac.uk          Melling, James: jmelling@liverpool.ac.uk
Jonchere, Vincent: jvais@liverpool.ac.uk Poster 7 Moss, Diana: dijim@liverpool.ac.uk Poster 18
Jones, Nic: njones@picr.man.ac.uk                    Murray, Raymond: MurrayR@Corning.com Corning
Chief Scientist, Cancer Research UK                  Naheet, Khalid: takeal1@liverpool.ac.uk
Kalirai, Helen: hkalirai@liverpool.ac.uk Poster 46   Najgebauer, Hanna: hanaj@liverpool.ac.uk
Kamalian, Laleh: laleh@liverpool.ac.uk               Neoptolemos, John: j.p.neoptolemos@liverpool.ac.uk
Kandola, Sandhir: skandola@liverpool.ac.uk           Director, Liverpool CRUK Centre
Poster 37                                            Newlaczyl, Anna: anewlacz@liverpool.ac.uk
Karosh, Heba: hkarosh@liverpool.ac.uk                Nicholson, James: jimbob82@liverpool.ac.uk
Kaur, Geetinder: gkaur@liverpool.ac.uk               Nithianandarajah, Gopika: gnithi@liverpool.ac.uk
Poster 9                                             Nwosu, Amara: amaranwosu@doctors.org.uk
Ke, Youqiang: yqk@liverpool.ac.uk                    Poster 41
Kenawy, Nihal: nkenawy@liverpool.ac.uk               Oliver, Simon: spoliver@liverpool.ac.uk
Poster 25                                            Palmer, Dan: palmerd@liverpool.ac.uk
Khalid, T: tyk247@liverpool.ac.uk                    Park, Kevin: bkpark@liverpool.ac.uk
Short Talk Speaker                                   Peeney, David: peeney1@liverpool.ac.uk
Kumar, Dinesh: vjdkumar@liverpool.ac.uk              Pettitt, Andy: arp@liverpool.ac.uk
Poster 35                                            Pizer, Barry: barry.pizer@alderhey.nhs.uk
Lake, Sarah: sarahl@liverpool.ac.uk Poster 36        Prior, Ian: iprior@liverpool.ac.uk
Lewis, Ian: ian.lewis@alderhey.nhs.uk                Pritchard-Jones, Rowan: rowanpj@liverpool.ac.uk
Medical Director, Alder Hey Children’s Hospital      Rajamanoharan, Dayani: dayani@liverpool.ac.uk
Lewys-Lloyd, John: lewysll@hotmail.com               Rawling, Louise: bs0u60f9@liverpool.ac.uk Poster 16
Chairman, North West Cancer Research Fund            Risk, Janet: mq25@liverpool.ac.uk
Liang, Amos: Jin-Rui.Liang@liv.ac.uk                 Robinson, Caspar: caspar.robinson@sial.com Sigma
Liloglou, Lakis: tliloglou@liverpool.ac.uk           Rogers, Mike: mike.rogers@cancer.org.uk
Lin, Ke: ha0p3002@liverpool.ac.uk                    Senior Research Funding Manager, Cancer Research
Lindsay, Derek: d.lindsay@redxpharma.com             UK                                                    31
Royle, Steve: sjroyle@liverpool.ac.uk Speaker
Rubbi, Carlos: cprubbi@liverpool.ac.uk
                                                     Sponsors
Rudland, Philip: rudland@liverpool.ac.uk
                                                     Many thanks to Novartis and Corning for providing
Sacco, Joseph: joesacco@liverpool.ac.uk              sponsorship.
Poster 22
Schache, Andrew: schache@liverpool.ac.uk
Short Talk Speaker
See, Violaine: violaine@liverpool.ac.uk
Seyed Forootan, Farzad: forootan@liverpool.ac.uk
                                                     Novartis is positioned to lead in innovation, partner
Seyed Forootan, Shiva: shifor@liverpool.ac.uk
                                                     with others and offer solutions to patients across a
Shahidipour, Haleh: bs0u5179@liverpool.ac.uk
                                                     broad healthcare spectrum. We believe our portfolio
Poster 6                                             best meets the varied and often complex needs of
Shaw, Richard: rjshaw@liverpool.ac.uk                patients and societies.
Shaw, Victoria: torivick@liverpool.ac.uk Poster 14
Simpson, Hannah: bs0u81fd@liverpool.ac.uk            www.novartis.com
Skellorn, Peter: md0u73b7@liverpool.ac.uk
Poster 12
Slupsky, Joseph: jslupsky@liverpool.ac.uk
Smith, Richard: rtsmith@liverpool.ac.uk
Stanbury, John: stanbury@liverpool.ac.uk
Stewart, Grant: g.s.stewart@bham.ac.uk
Guest Speaker
Sykes, Paul: pdsykes@liverpool.ac.uk
Talab, Fatima: fat@liverpool.ac.uk
Tang, Yvonne: xadroit@liverpool.ac.uk Poster 2
                                                     Corning’s leading-edge scientific laboratory
Tayeb, Faris: ftayeb90@liverpool.ac.uk
                                                     products improve productivity, enabling the
Turner, Lorraine: leturner@liverpool.ac.uk
                                                     development of breakthrough pharmaceutical
Tweedle, Liz: etweedle@liverpool.ac.uk               discoveries.
Upile, Navdeep: nupile@liverpool.ac.uk
Poster 42                                            www.corning.com/lifesciences/emea/en
Urbé, Sylvie: urbe@liverpool.ac.uk
Varro, Andrea: avarro@liverpool.ac.uk Speaker
Vlatkovic, Nikolina: vlatko@liverpool.ac.uk
Wang, Liyi: liyi@liverpool.ac.uk Poster 33
Wardyn, Joanna: jdwardyn@liverpool.ac.uk
Waters, Aoife: awaters@liverpool.ac.uk Poster 40
Williams, Samantha: sjw@liverpool.ac.uk
Wilson, James: jwilson@liverpool.ac.uk
Winn, Simon: sawinn@liverpool.ac.uk
Wong, Jia Lih: jlwong@liverpool.ac.uk Poster 5
Yan, Li: qili223@liverpool.ac.uk Poster 17
Yu, Lugang: lgyu@liverpool.ac.uk
                                                                                                             32
Zhuang, Jack: jzhuang@liverpool.ac.uk
Liverpool Cancer Research UK Centre
        200 London Road, Liverpool
                  L3 9TA, UK
   Web: w w w.liverpoolcancercentre.org.uk
             Tel: 0151 794 8823

				
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