6th ICHNO Abstract Book

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page 50 6th ICHNO
6 th ICHNO Conference
International Conference on innovative approaches in Head and Neck Oncology
16 – 18 March 2017
Barcelona, Spain
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Results
To date, tumor biopsies from 24 OPSCC patients have been
xenografted resulting in xenograft tumor growth in 15
cases (63 %). PDX models were established from OPSCC
patients with HPV-positive and HPV-negative disease as
well as a wide range of tobacco exposure. Most PDX tumors
retained the histological appearance of squamous cell
carcinoma and immunoprofile of the original tumor. Other
tumors adopted a lymphoproliferative appearance. Low-
dose irradiation of PDX tumors resulted in a reproducible
growth delay.
Conclusion
It is possible to generate PDX models that represent the
clinical heterogeneity of disease with a satisfactory
success rate. Most PDX models retain the characteristics
of the original tumor. The PDX model is suitable for
radiotherapy research.
PO-104 Everolimus in oral cancer: a potential
therapeutic approach dependent on cell type?
C. Domingues1,2,3, P. Matafome4, S. Neves2,3, M. Laranjo3,5,
R. Seiça4, M.F. Botelho 3,5, A.B. Sarmento-Ribeiro 2,3, M.
Dourado1,3
1Faculty of Medicine- University of Coimbra- Portugal,
Pathophysiology Curricular Unit- Dental Medicine,
Coimbra, Portugal
2Faculty of Medicine- University of Coimbra- Portugal,
Laboratory of Oncobiology and Hematology- Applied
Molecular Biology and University Clinic of Hematology,
Coimbra, Portugal
3Faculty of Medicine- University of Coimbra- Portugal,
Center of Investigation on Environment Genetics and
Oncobiology CIMAGO, Coimbra, Portugal
4Faculty of Medicine- University of Coimbra- Portugal,
Laboratory of Physiology- Institute for Biomedical
Imaging and Life Sciences IBILI, Coimbra, Portugal
5Faculty of Medicine- University of Coimbra- Portugal,
Biophysics Institute- Institute for Biomedical Imaging and
Life Sciences IBILI, Coimbra, Portugal
Purpose or Objective
Oral squamous cell carcinoma (OSCC) is the most common
cancer of oral cavity with poor prognosis and survival
rates. The PI3K/AKT/mTOR signaling pathway plays a
central role in cell proliferation, migration, survival and
angiogenesis regulation. Recently, the aberrant activation
of mTOR has been connected with poor prognosis in
various cancers including OSCC, becoming a promising
anti-cancer target therapy.
The main objective of this study was to evaluate, in vitro,
the therapeutic efficacy of a mTOR inhibitor, everolimus
(EVE), in OSCC and the related underlying mechanisms.
Material and Methods
Two OSCC cell lines were maintained in culture, BICR-10
(in situ ) and the HSC-3 (high metastatic potential) cells,
in absence and in presence of increasing concentrations of
EVE, 10-50 µM. Cell viability was assessed by the rezasurin
metabolic assay and cell death by optical microscopy
(May-Grünwald-Giemsa staining) and flow cytometry
(Annexin V-Propidium Iodide staining). Cell cycle was
assessed by flow cytometry using PIRNase kit. The
Caspases, BAX, BCL-2, Cyclin D1 and E-cadherin expression
levels were also evaluated by flow cytometry. Western
blot was used to evaluate the expression of total and
phosphorylated AKT and P70S6K as well as the total
expression of Integrin Beta 1 and Beta 1 Catenin. Cell
migration was evaluated by the wound healing assay.
Enzymatic activity of metalloproteinase (MMP)-2 and -9
was evatuated by zymography. Results were statistical
analyzed.
Results
Our results showed that EVE induces antiproliferative and
cytotoxic effects in a dose, time and cell type dependent
manner. The HSC-3 cells were the more sensitive to EVE,
with IC50 at 48h around 35µM. In HSC-3 cells EVE induced
cell death mainly by later apoptosis/necrosis associated to
the increase in BAX/BCL-2 ratio and Caspases levels.
Furthermore, EVE induced cell cycle arrest in S phase with
the increase in Cyclin D1 expression. EVE also reduced
migration and invasion in HSC-3 cells dependent on the
following: increase of E-Cadherian expression and
decrease of both Integrin beta 1 expression and MMP-2
enzymatic activity.
Conclusion
In this work, we did not observe significant statistical
alterations in the OSCC in situ cells treated with EVE.
However, in OSCC cells with high metastatic potential we
observed that EVE induced a significant statistical
decrease in cell proliferation, migration, invasion and an
increase in cell death. These results suggest that EVE
constitutes a promising therapeutic approach in OSCC with
high metastatic potential.
PO-105 Is there justification for age bias in HPV p16
testing for Oropharyngeal Squamous Cell Carcinoma?
S. McCauley 1, P. McCloskey1, C. Lyons1, K. Brown1, K.
Rooney1, F. Houghton1
1Northern Ireland Cancer Centre, Clinical Oncology,
Belfast, United Kingdom
Purpose or Objective
Human Papilloma Virus (HPV) p16 is a causative agent in a
biologically distinct subset of Oropharyng
eal Squamous Cell Carcinoma (OPSCC), with a highly
favourable prognosis 1. Updated guidelines pertaining to
OPSCC now require universal HPV p16
immunohistochemistry testing2. Using this as our standard,
we undertook a retrospective audit of all OPSCC treated
in our centre during 2015, identifying the prevalence of
OPSCC in our population, p16 status, the proportion of p16
positivity, and their age-gender demographics. We