Surgicalresearch.org.uk

ORAL PRESENTATION 4A
MEDICAL STUDENT PRIZE

O117 EXPRESSION OF HEPATOCYTE GROWTH FACTOR-LIKE/MACROPHAGE
STIMULATING PROTEIN IN HUMAN WOUND TISSUE AND ITS BIOLOGICAL
FUNCTIONALITY IN HUMAN KERATINOCYTES
JCD Glasbey, AJ Sanders, F Ruge, KG Harding, WG Jiang
Metastasis & Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff
University School of Medicine, Heath Park, Cardiff

Introduction
Chronic wounds represent a significant burden of morbidity to global healthcare systems.
Exploration of the pathogenesis of chronic non-healing and relevant biomarkers will
facilitate targeted therapeutics. Hepatocyte growth factor-like/Macrophage stimulating
protein (HGFl/MSP) is a growth and motility factor mediated by the RON/STK receptor
tyrosine kinase. It has roles described in tissue repair, embryonic development and cancer
progression. We propose a novel role for HGFl/MSP as a pro-migration factor in a human
keratinocyte (HaCaT) cell line and propose a pathway for this activity.
Methods
Transcript levels of HGFl/MSP in human acute and chronic wound tissue samples were
quantified. The biological response of human keratinocytes to recombinant HGFl/MSP was
interrogated using in-vitro scratch-wound and cell-growth assays and an electric cell-
substrate impedance sensing-based (ECIS) model system with inhibitors to candidate
signalling pathways.
Results
HGFl/MSP expression was significantly higher in acute human wound tissue in comparison
to chronic tissue samples (p<0.05). Recombinant human HGFl/MSP augmented the rate of
keratinocyte migration (p<0.05) in a concentration-dependent fashion, but had negligible
effects on rates of cell growth. The pro-migration effect of HGFl/MSP was negated following
addition of focal adhesion kinase (FAK) and phospholipase C-gamma (PLC-γ) pathway
inhibitors (p<0.005).
Conclusion
We conclude that HGFl/MSP promotes the migratory behaviour of human keratinocytes
through a PLC-gamma and FAK-dependent pathway. Defects in this pathway may
contribute to wound chronicity and thus constitute reasonable therapeutic targets.
Take-home message
HGFl/MSP promotes the migratory behaviour of human keratinocytes through a PLC-
gamma and FAK-dependent pathway. Defects in this pathway may contribute to wound
chronicity and thus constitute a reasonable therapeutic target.

O118 THE EFFECT OF VARYING DOSES OF CAFFEINE ON LAPAROSCOPIC SKILL
PERFORMANCE IN NOVICES
V Quan, W Elbakbak, A Gavrila, B Alaraimi, A Bouhelal, B Patel
Barts Cancer Institute, Queen Mary University of London

Introduction
Our aim is to observe the effect of caffeine on performing laparoscopic skills in novices
within a simulated setting and if this is dose dependent. Coffee is consumed almost
ubiquitously by surgeons; thus it was worth investigating its potentially negative effect on
performance of laparoscopic skills. As it has been known for coffee to have motor effects,
we investigated whether this effect was statistically significant or not.
Methods
A primary prospective study in which 28 novices were tested under three different
conditions: decaffeinated, 100mg caffeine and 200mg caffeine. Candidates were asked to
perform 3 repetitions of task 3, 6, 7 and 8 using the Lap Mentor™ (Simbionix®).
Outcomes measured were completion time, accuracy, number of movements and total
path length. The candidates were crossed over to the other caffeine doses on a different
day.
Results
17 candidates completed the study, mean age 22.4 years with 8 males and 9 females.
There were no significant differences in task 3 and 6. Candidates performed task 7 and 8
faster in the decaffeinated group than the caffeinated groups with significant difference
between decaffeinated and 100mg caffeine (p value=0.004, 0.049 respectively), but there
were no significant results between decaffeinated and 200mg caffeine (p value=0.071,
0.188). The number of movements and the path length were also significantly less in the
decaffeinated group.
Conclusion
Caffeine had no effect on laparoscopic performance for basic tasks (task 3, 6), but had a
negative effect on advanced tasks (task 7, 8) although the difference was not dose
dependent.
Take-home message
Coffee is the most common stimulant consumed by surgeons and as such we should be
aware of its effects on surgical performance. We have shown that coffee can have a
negative impact on performance of laparosopic tasks in novices on a simulator.

O119 A PILOT STUDY INVESTIGATING THE ABILITY OF ADVANCED BIPOLAR RF
DEVICE TO INDUCE BLOOD VESSEL HAEMOSTASIS BY ACTIVATION OF THE
COAGULATION PATHWAY
M Elsaddig (1), S Arya (1), M H Kudo (2), RD Goldin (2), G Hanna (1)Division of Surgery,
Department of Surgery and Cancer, Imperial College London, St. Mary's Hospital, 10th
Floor, QEQM Building, South Wharf Road, London (1) Centre for Pathology, Department of
Cellular Pathology, St. Mary’s Hospital, South Wharf Road, London, W2 1NY (2)
Introduction
Traditional surgical haemostasis techniques can be associated with some morbidity. Bipolar
radiofrequency (RF) induced vessel sealing is an energy-based method and is understood
to produce seals by thermal denaturation of extracellular matrix proteins within the vessel
wall, in doing so RF can induce thermal damage. It has been observed (unpublished
results) that LigaSure™ also shows signs suggestive of activation of the coagulation
system. This study aimed to determine whether advanced bipolar radiofrequency device
(LigaSure™) activates the blood coagulation system.
Methods
Short gastric branches were ligated by suture/clip (control) or LigaSure™ (experiment) at
open oesophagectomy (two patients). The tissues were cut to 18, 0.3-0.5cm segments,
including the fusion area. Each segment was stained using four histological stains:
Haematoxylin and Eosin, Elastic Van Gieson, Sirius Red, Martius Scarlet Blue and two
immunohistochemical stains: Anti-CD34 and Anti-CD141 (thrombomodulin). The slides
were assessed qualitatively and qualitatively under light microscopy.
Results
H&E staining revealed flatted nuclei in the LigaSure™ fusion region. SR showed
interdigitation of collagen at the RF-fusion area. EVG showed maintenance of elastin
despite ligation in both groups. MSB stained fibrin in distal LigaSure™ segments. Despite
the anti-CD34 stain being reduced in the most proximal section, the overall stain uptake
with LigaSure™ is maintained. However, the uptake of the anti-CD141 staining is greatly
reduced proximally (p=0.044). The overall ratio of anti-CD141 to anti-CD34 staining
increased with increasing distance from the site of LigaSure™ application.
Conclusion
The results support the hypothesis that bipolar RF energy seals vessels by activation of the
coagulation cascade.
Take-home message
The study displayed microscopical changes with RF application and presented evidence of
consumption of anti-coagulation proteins. This can be used in improving the precision of
the device and the jaw design.

O120 NUTLIN-3 IS CYTOTOXIC IN TP53 WT LIPOSARCOMA AND
LEIOMYOSARCOMA IN VITRO AND CAN ACT BOTH SYNERGISTICALLY AND
ANTAGONISTICALLY WITH IONISING RADIATION
HDJ Hogg (2), JJ French (1), J Lunec (2)
Northern Institute for Cancer Research, Newcastle (2) and Freeman Hospital, Newcastle
(1)
Introduction
MDM2-p53 binding antagonists have shown efficacy as a monotherapy for liposarcoma in
clinical trials and as a radiosensitising agent in other cancer lines in vivo. Our aim is to
confirm the TP53 dependency of MDM2-p53 binding antagonists and to characterise the
interaction between MDM2-p53 binding antagonists and irradiation in liposarcoma and
leiomyosarcoma cell lines.
Methods
6 liposarcoma and 3 leiomyosarcoma cell lines had their sensitivity to Nutlin-3, an
established MDM2-p53 binding antagonist, and X-irradiation monotherapies investigated
by clonogenic cell survival and sulforhodamine-B (SRB) growth inhibition assays. The
sensitivity to combination therapy was investigated over a range of fixed dose ratios. The
combination index (CI) for each datapoint was derived using CalcuSyn software to
determine the nature of the therapeutic interaction.
Results
TP53 wild-type (WT) cell lines (n=5) were highly sensitive to Nutlin-3 (median
GI50=1.14µM ±0.26µM) whereas all TP53 mutant cell lines were resistant with a GI50>10
µM. In contrast, TP53 status held no predictive value for radiosensitivity. Similarly, Nutlin-
3 interacted with irradiation only in TP53 WT cell lines. This interaction was shown to be
synergistic (CI<1) in all TP53 WT cell lines at certain ratios but antagonistic at others.
Conclusions
Nutlin-3 cytotoxicity is p53 dependent in all examples of liposarcoma and leiomyosarcoma
tested here. The nature of the interaction between Nutlin-3 and ionising radiation is
dependent on dose levels and ratios, but synergism was achieved in all TP53 WT cell lines.
Take-home message
In vitro demonstration of the sensitivity of TP53 wild type liposarcomas and
leiomyosarcomas to MDM2-p53 binding antagonists both as a monotherapy and
additionally as a radiosensitiser. This developing targeted therapy holds promise as an
adjuvant therapy for these mainly surgically managed malignancies.

O121 THE ASSOCIATION OF VISCERAL ADIPOSITY WITH ABDOMINAL AORTIC
ANEURYSM PRESENCE, SIZE AND EX-VIVO FIBRIN CLOT STRUCTURE
JA Batty, MA Bailey, A Adeogun, K Fairbrass, KI Bridge, AB Johnson, PG Walker, RAS
Ariëns, DJA Scott.
Leeds Vascular Institute, the General Infirmary at Leeds, Leeds, UK

Introduction
Although obesity has been putatively associated with abdominal aortic aneurysm (AAA)
development, the underlying mechanism remains uncertain. There are few data regarding
the association of visceral adiposity with coagulation dysfunction and AAA size.
Methods
A 1:1 case-control analysis (n=1076) evaluated the association between anthropometric
measures of obesity (body mass index, BMI; waist-to-hip ratio, WHR) and aneurysm
status. In an AAA sub-population (n=32), abdominal computed tomography images were
available for semi-automated visceral-to-superficial adipose ratio analysis (V/S; Analyze
11.0). Detailed characterisation of aneurysm structure (multi-level polygonal
segmentation; AAA Analyser 5.2), and extensive ex vivo plasma clotting analyses (fibrin
permeation, confocal microscopic fibre density) were undertaken. Associations were
evaluated using multilevel linear regression (SPSS 20.0). Data are presented as median,
interquartile range.
Results
Anthropometric measures of abdominal (but not generalised) adiposity were strongly
associated with AAA presence (cases vs. controls: WHR 0.97 vs. 0.93; p=0.004; BMI, 27.3
vs. 27.5kgm-2; p>0.05). 87.5% had predominantly visceral (V/S ≥0.40) adipose
distributions (0.74, 0.47-1.03), with high abdominal visceral fat areas (157.0, 108.5-
233.9cm2; ≥110cm2 associated with elevated cardiovascular risk). Participants with
visceral-type distributions had larger aneurysms measured by diameter (6.70 vs. 5.55cm,
p=0.03) and volume (226.41 vs. 168.76cm3, p=0.007). Average optical plasma clot fibre
density was greater in visceral obesity (34.1 vs. 28.8 120μm-1, p=0.02); with
correspondingly-lower clot permeability (4.78 vs. 5.65×10-9cm2, p=0.04).
Conclusion
Visceral adiposity was more common in AAA patients, associated with larger AAAs and
clotting disturbances. Further work should focus on the effect of visceral adiposity on AAA
growth. This study supports lifestyle advice to AAA patients.
Take-home message
Abdominal obesity is common in patients with abdominal aortic aneurysm (AAA). Indices
of visceral adiposity are putatively associated with larger aneurysm size, and ex-vivo
clotting disturbances.

O122 ANATOMICAL EXAMINATION OF THE ELBOW TO DETERMINE IF IT IS A
POTENTIAL SOURCE OF VASCULARISED TISSUE FOR RECONSTRUCTION
S Hettiaratchy, C Read
Imperial College Human Anatomy Unit

Introduction
Greater anatomical understanding has led to the era of ‘perforator flaps’ meaning that
reconstructive surgeons can raise flaps from virtually any site in the body, improving
aesthetic and functional outcomes. We investigated perforators off two potentially
applicable collateral vessels in the elbow (the superior (SUCA) and inferior (IUCA) ulnar
collateral arteries) and their potential to form the basis of free flaps.
Methods
In 10 formalin-fixed cadaveric upper limbs, the SUCA, IUCA and their cutaneous
perforators were identified. Each vessel was dissected to the origin of its major vessel. The
pedicle length (L) (the perforator and its collateral vessel); the distance from the medial
epicondyl to the collateral vessel’s origin (Dc) and the perforators from their penetration
into the superficial fascia (Dp); and the diameter of the collateral vessels (d) were all
measured using a digital calliper.
Results
For the SUCA, the mean values obtained for the Dc, Dp, L and d were 15.00±4.02cm,
8.87±2.92cm, 5.39±2.77cm and 3.64±0.88mm, respectively. On average, 1.8±0.63
perforators were associated. For the IUCA, the mean values obtained for the Dc, Dp, L and
d were 4.27±1.57cm, 2.73±1.49cm, 3.66±1.58cm and 3.17±0.70mm respectively. On
average, 1.00±0.00 perforators were associated. Anatomical variation was found in 40%
of cadavers.
Conclusion
Perforators associated with the SUCA and IUCA were consistently and reliably found. To
the best of our knowledge, this is the first report describing the potential use of both these
collaterals and their perforators as the basis of free flaps in small-medium sized defects
requiring thin, pliable, hairless skin.
Take-home message
Free flaps based upon arteries and their perforators found around the elbow such as the
superior or inferior ulnar collateral arteries can potentially be used for small-medium sized
defects requiring thin, pliable and hairless skin.

O123 EXOSOME-MEDIATED ACTIVE AND SELECTIVE SECRETION OF MICRORNAS
BY BREAST CANCER CELLS IN VITRO.
LS Rahmani (1), CL Glynn (2), RM Dwyer (2), MJ Kerin(2)
School of Medicine, Clinical Science Institute, National University of Ireland, Galway (1),
Discipline of Surgery, School of Medicine, National University of Ireland, Galway (2)

Introduction
MicroRNAs are small non-coding RNA molecules, which modulate gene expression post-
transcriptionally, and can be dysregulated in many diseases, including breast cancer. Given
their recent potential as disease biomarkers, molecular mechanisms underlying microRNA
secretion and transfer must be understood to elucidate their role in tumourigenesis.
Exosomes potentially provide a novel transport mechanism for the delivery of microRNAs
between different cell populations. This study aimed to determine if microRNAs are actively
and selectively secreted by exosomes in breast cancer cells In Vitro.
Methods
Three breast cancer cell lines (T-47D, SK-BR-3, BT-20), obtained from the American Type
Culture Collection®, were cultured in exosome-depleted culture media. Following
incubation, cell-conditioned media containing all factors secreted by cells was harvested.
Differential high-speed ultracentrifugation was used to isolate exosomes from cell-
conditioned media. Remaining cell-conditioned media was collected and cells pelleted.
MicroRNAs were extracted using the mirVana™ miRNA Isolation Kit and their quantity
determined using the NanoDrop™ Spectrophotometer. cDNA was synthesised and RQ-PCR
performed targeting microRNAs of interest (miR-16, miR-138, miR-379, miR-504) and the
ability to detect their presence was determined.
Results
MiR-16 and miR-379 were detectable in matching exosome pellets, cell-conditioned media
and cell pellets from T-47D, SK-BR-3 and BT-20 cell lines. MiR-138 was detectable in
exosome pellets and cell-conditioned media only from the BT-20 cell line and cell pellets
from T-47D, SK-BR-3 and BT-20 cell lines, demonstrating selective microRNA secretion.
MiR-504 was undetectable in all samples.
Conclusions
This study suggests that microRNAs are actively and selectively secreted within exosomes
by breast cancer cells In Vitro.
Take-home message
The secretion of microRNAs by breast cancer cells In Vitro has been shown to be active
and selective within exosomes. This is of vital importance as the exact mechanisms
underlying microRNA secretion have been relatively unknown to date.

O124 REDUCED GLYCOSYLATION OF SKBR3 BREAST CANCER CELLS AFFECTS
RESPONSE TO TREATMENT
AF Spector, B Ramesh, M Loizidou, M Dwek, H Welch
UCL Medical School, Royal Free Campus
Introduction
Many cancer types including Breast, Lung, and Colorectal display increased glycosylation
which is associated with enhanced aggression and metastasis. While the adverse effects on
prognosis are well documented, the effects on response to treatment remain largely
unexplored. To investigate how the glycocalyx affects response to chemotherapeutics and
growth factors, SkBr3 breast cancer cells were treated with the N-linked glycosylation
inhibitor Tunicamycin.
Methods
SkBr3 cells were maintained in Tunicamycin at 1mg/mL (SkBr3-T) for 6/8 weeks prior to
comparison with non-treated cells (SkBr3-UT) in 10% FBS-McCoy’s. Lectin conjugated
Quantum Dot (QD) fluorescence and QD-tagged EGFR-antibody, with confocal microscopy,
were used to compare glycosylation levels between SkBr3-T and SkBr3-UT cells. The
effects of Doxorubicin and growth factors (IGF-1 and EGF, ±E2) were determined by
metabolic activity using MTT assays.
Results
Significantly reduced levels of total glycosylation were observed in SkBr3-T cells compared
with SkBr3-UT cells (80% reduction, p<0.05). Additionally, glycosylated EGFR levels were
reduced in SkBr3-T cells (55% reduction, p<0.05). SkBr3-T cells displayed increased
susceptibility to Doxorubicin at 100nM (p<0.05) and were less responsive to IGF-1 and
EGF ±E2 (p<0.001) compared with SkBr3-UT cells.
Conclusions
These results indicate that reducing the glycosylation load of SkBr3 cells increases their
susceptibility to Doxorubicin while also reducing their responsiveness to growth factors,
perhaps due to reduced receptor levels. The reduced EGFR level is of particular interest as
it is overexpressed in many cancers and the focus of anti-cancer therapy.
Take-home message
Manipulating the glycosylation profile may have a role in the development of future breast
cancer therapies.

O125 ENHANCED MESENCHYMAL STEM CELL IMMUNOMODULATORY POTENCY
THROUGH INTRACELLULAR BUDESONIDE MICROPARTICLES
JF Ong, JA Ankrum, RG Dastidar, O Levy, JM Karp
Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women’s
Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences & Technology,
Harvard Stem Cell Institute

Introduction
MSC are being explored to treat numerous inflammatory pathologies, but clinical studies
have yielded mixed results, likely due to variability in MSC potency. Here we show that
budesonide significantly augments MSC expression of IDO , a primary mediator of MSC
immunomodulatory function. We additionally describe a strategy to continuously expose
MSC to budesonide using intracellular microparticles, potentially allowing control over MSC
potency post-translation. This could be employed in conditions such as IBD and tissue
allograft rejection in reducing the surgical burden and the side-effects of
immunosuppression.
Methods
To simulate the inflammatory environment, human MSC were pre-treated with IFN-γ. IFN-
γ-MSC were treated with free budesonide, budesonide-MP and blank MP. The
immunosuppressive effects of IFN-γ-MSC were assessed by quantifying IDO expression
and by co-culturing them with PBMC stimulated by CD3/CD28 Dynabeads.
Results
Free budesonide increased IFN-γ-MSC IDO expression. Continuous exposure of IFN-γ-MSC
to budesonide was achieved by allowing MSC to internalise budesonide-MP. Compared with
blank MP, internalised budesonide-MP increased IDO expression 5-fold. During co-culture,
BUD-MSC decreased proliferation of and IFN-γ secretion by stimulated PBMC. Inhibition of
IDO by 1-methyl-tryptophan completely abolished these effects, implicating IDO as a
primary mediator of BUD-MSC immunosuppressive effects.
Conclusion
Intracellular microparticles that continuously release drugs to the host cell may offer
stronger and longer-term enhancement of cellular function, compared with ex vivo small
molecule pre-treatment. Given the ubiquitous benefits of IDO in inflammatory conditions,
our strategy may improve the efficacy of MSC therapy in multiple clinical indications.
Take-home message
Intracellular small molecule pre-treatment provides a promising approach to enhancing
and controlling mesenchymal stem cell (MSC) phenotype for use in cellular therapy. The
significant augmentation of MSC immunosuppressive capability through IDO expression
could potentially be used in multiple inflammatory conditions such as Inflammatory Bowel
Disease and transplant allograft rejection, by complementing or replacing systemic
immunosuppression and surgery.

O126 SEX DIFFERENCES IN FEATURES OF ANORECTAL DYSFUNCTION: A
CONSECUTIVE STUDY OF 100 MALES AND 100 FEMALES PRESENTING FOR
INVESTIGATION OF FAECAL INCONTINENCE
DC Townsend (1,2), EV Carrington (1,2), R Burgell (1,2), EJ Horrocks (1,2), SM Scott
(1,2), CH Knowles (1,2).
National Centre for Bowel Research and Surgical Innovation (NCRBSI) (1), GI Physiology
Unit, The Wingate Institute (2), Barts and the London School of Medicine and Dentistry,
Queen Mary, University of London, United Kingdom
Introduction
Faecal incontinence (FI) is a widespread and socially disabling condition. Recent
epidemiological studies indicate that prevalence of male FI may be greater than previously
recognised. This study aimed to systematically identify differences in symptom
presentation and anorectal function between men and women referred to a tertiary centre.
Methods
Data were prospectively collected on 100 male and 100 female patients consecutively
undergoing full clinical and anorectal physiological assessment. Data included: symptom
profile and severity; and investigation findings (anal manometry, rectal sensation,
pudendal nerve function, endoanal ultrasound and evacuation proctography).
Results
Patient groups were similar with regards to age (male: median 56 years [range 16-83] vs.
female: 58 [25-85] P=0.36). Males had a higher incidence of prior anorectal surgery (32
vs. 16%, P=0.008) but lower incidence of pelvic surgery (0 vs.16%, P<0.001). Symptom
severities were similar (St Marks’ incontinence score; male 12±5 vs. female 13±6
P=0.868); however, males were less likely to present with symptoms of passive
incontinence (57 vs. 71%; P=0.039). Men had less frequent findings of abnormal anal
resting pressures (14 vs. 21%, P=0.037), squeeze increments (12 vs. 47%, P<0.001),
internal (36 vs. 68%, P<0.001) and external anal sphincter morphology (16 vs. 74%;
P<0.001). However more males exhibited rectal hyposensitivity (16 vs. 12%, P=0.03) and
outlet dysfunction during evacuation proctography (57 vs. 13%; P<0.001). No females,
but 11% males had no abnormality detected (P=0.001).
Conclusions
Despite presenting with similar symptoms of equal severity, men and women differed with
regards to anorectal physiological abnormalities. This may have implications for
management.
Take-home message
Despite presenting with similar symptoms of equal severity, men and women differed with
regards to anorectal physiological abnormalities. This may have implications for
management.
O127 GLIOMA STEM CELLS EXPLOIT HOST ASTROCYTES TO ENHANCE TUMOUR
MIGRATORY AND INVASIVE CAPACITY
A Khajuria (1,2), Tabu K (2), Taga T (2)
Imperial College London School of Medicine (1), Department of Stem Cell Regulation,
Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan (2)

Introduction
Glioblastoma Multiforme (GBM) is the most aggressive neurological malignancy. Invasion
into healthy brain parenchyma confers GBM’s resistance to surgical resection. Literature
suggests that tumour cells can exploit host astrocytes by altering gene expression to
enhance tumour invasion. We investigated the role of Glioma stem cells (GSCs) defined as
side population (SP) cells in this interaction.
Methods
Astrocytes were cultured alone, with SP cells or non-SP cells purified from C6 glioma cell
line. The conditioned medias were placed in lower compartments of transwell chambers
with fresh SP cells in upper compartments to investigate GSC migration. For investigating
invasion, fresh SP cells were suspended in the three conditioned medias and placed in
upper compartments of matrigel chambers. Following incubation, migrated and invaded
cells onto lower membrane were stained and counted. Astrocytes were isolated using flow
cytometry and co-transplanted with fresh SP cells via intracranial transplantation into
nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice. Brain slices were
subjected to Hematoxylin&Eosin staining. Gene expression was investigated using RT-PCR.
Results
SP-educated astrocytes, compared to uneducated astrocytes (cultured alone), enhanced
SP migratory (177±19 vs 39±8 migrated cells, p<0.01) and invasive capacity (213±17 vs
37±16 invaded cells) with upregulation of TGFβ1 and MMP9 genes. In-vivo analysis
supported these findings for invasion. GSC-educated astrocytes induced morphological
transformation in migrated SP cells, with increased number (41±4 vs 11±3, p<0.01) of
cell processes.
Conclusion
Further investigation of GSC-astrocyte interaction could propose a potentially novel anti-
invasive therapeutic target, which thereby may retard GBM invasion and enhance the
efficacy of surgical resection.
Take-home message
GSCs can exploit host astrocytes to enhance tumour migratory and invasion capacity, both
in-vitro and in-vivo. Further examination of this functional interaction could propose
potentially novel, anti-invasive targets to improve prognosis of patients with GBM.

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