مجال
التميز
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تميز دراسي وبحثي +
جائزة تفوقية
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البحوث
المنشورة
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البحث (1):
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عنوان البحث:
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A top-down view of the tumor microenvironment: structure, cells and
signaling
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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29/05/2015
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موجز عن البحث:
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It is well established that the tumour microenvironment (TME)
contributes to cancer progression. Stromal cells can be divided into
mesenchymal, vascular, and immune. Signalling molecules secreted by the tumour
corrupts these cells to create “activated” stroma. Equally, the
extracellular matrix (ECM) contributes to tumour development and invasion by
forming a biologically active scaffold. In this review we describe the key
structural, cellular and signalling components of the TME with a perspective
on stromal soluble factors and microRNAs (miRNAs).
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البحث (2):
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عنوان البحث:
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Translational aspects in targeting the stromal tumour microenvironment:
from bench to bedside
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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28/03/2016
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موجز عن البحث:
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Solid tumours comprise, not only malignant
cells but also a variety of stromal cells and extracellular matrix proteins.
These components interact via an array of signalling pathways to create an
adaptable network that may act to promote or suppress cancer progression. To
date, the majority of anti-tumour chemotherapeutic agents have principally
sought to target the cancer cell. Consequently, resistance develops because
of clonal evolution, as a result of selection pressure during tumour
expansion. The concept of activating or inhibiting other cell types within
the tumour microenvironment is relatively novel and has the advantage of
targeting cells which are genetically stable and less likely to develop
resistance. This review outlines key players in the stromal tumour
microenvironment and discusses potential targeting strategies that may offer
therapeutic benefit.
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المؤتمرات العلمية:
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المؤتمر (1):
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عنوان المؤتمر:
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The VI International Epithelial Mesenchymal Transition Meeting
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تاريخ الإنعقاد:
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13-16/11/ 2013
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مكان
الإنعقاد:
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Alicante. Spain
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طبيعة المشاركة:
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Poster Presentation
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عنوان المشاركة:
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ZEB1 induced EMT defines poor prognosis in hepatocellular carcinoma
and facilitates selective elimination of metastatic HCC by UCN-01
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ملخص المشاركة:
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Hepatocellular carcinoma (HCC) is one of the most common and deadly
cancers. Intra- and extra-hepatic metastases are the main reason for HCC related
mortality. Currently, there are no biomarkers of occult metastasis or any
effective therapeutic strategies for metastatic HCC. Epithelial-mesenchymal
transition (EMT) is a developmentally conserved trans-differentiation
programme that plays a major role in cancer spread by inducing formation of
highly invasive and motile cancer cells. Equally important, cancer cells that
have undergone EMT are resistant to conventional chemotherapy. Identifying
and targeting this pool of tumour cells is a major challenge in cancer
research.
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المؤتمر (2):
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عنوان المؤتمر:
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7th Saudi students’ Conference (SSC2014)
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تاريخ الإنعقاد:
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1-2/02/2014
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مكان
الإنعقاد:
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Edinburgh. UK
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طبيعة المشاركة:
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Poster Presentation
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عنوان المشاركة:
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ملخص المشاركة:
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The presence of metastatic or invasive cancer cells has been proposed
to predict poor patient outcome. Similarly, the presence of certain types of
immune cells, infiltrating the primary cancer, are linked with patient survival
and therefore metastasis. However, whether 1- metastatic cells can alter the
tumour microenvironment by secreting soluble factors that define immune
infiltrate or 2- certain immune cells infiltrate the primary tumour and
induce EMT by secreting cytokines/chemokines and therefore induce metastasis,
is not clearly understood. For the reason that metastatic cells can be
detected very early during tumorigenesis, and even in some cases distant
metastasis can occur without any sign of a primary tumour, we reasoned that
metastatic cells have a bigger influence on the immune filtrate. To address
this question, we performed a screen to qualitatively investigate 67
chemokines and cytokines using the DLD-SIP1-inducible EMT model and a panel
of CRC cell lines. CCL5 is the
candidate chosen from the array, with a set of selective criteria in order to
test the hypothesis of the project. CCL5 is more highly expressed after
induction of the SIP1 gene in DLD-SIP-1 cells, and in the mesenchymal CRC
cell lines expressing ZEB1/2. ZEB1/2 have been strongly implicated in CRC
metastasis and are associated with poor patient survival. Therefore, I have
proposed that CCL5 might be up-regulated upon induction of ZEB1/2 in
carcinoma cells making EMT and metastasis possible by escaping immune
destruction. Understanding the mechanistic and the functional role of ZEB1/2
in driving CCL5 expression, and highlighting the benefit of targeting CCL5
could be essential in improving cancer therapy.
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المؤتمر (3):
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عنوان المؤتمر:
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Burden of Cancer in the Gulf Region Conference
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تاريخ الإنعقاد:
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21-23/10/2014
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مكان
الإنعقاد:
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Riyadh, KSA
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طبيعة المشاركة:
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Paper presentation
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عنوان المشاركة:
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The biological contribution of SIP1 to metastasis and chemo-resistant
pathways in Colorectal cancer
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ملخص المشاركة:
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Epithelial-Mesenchymal Transition (EMT) is an embryologically
conserved trans-differentiation program by which epithelial cells lose their
ability to form epithelial junctions, become mesenchymal, and manifest a
migratory phenotype. While the
significance of EMT during development and embryogenesis is well established,
compelling evidence has emerged in recent years highlighting a role,
promoting metastasis and chemo-resistance in the cancer setting. EMT is
activated by TGFβ, EGF, Wnt and Notch signaling pathways, which converge to
activate transcription factors that subsequently promote cellular phenotypic
switch. Key transcription factors in this process include members of the
SNAI, Twist, and ZEB families. In addition to enhanced migration, metastatic
cells also acquire resistance to apoptotic stimuli, through as yet poorly
understood mechanisms. Among EMT inducing transcription factors, SIP1 (ZEB2)
is the least studied in general. Subsequently we studied the role of SIP1 at
mediating metastasis and chemo-resistance in the setting of CRC.
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المؤتمر (4):
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عنوان المؤتمر:
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8th Saudi students’ Conference (SSC2015)
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تاريخ الإنعقاد:
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01/02/2015
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مكان
الإنعقاد:
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London. UK
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طبيعة المشاركة:
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Poster Presentation
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عنوان المشاركة:
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The Mechanistic Role of ZEB1/2 EMT in Activating CCL5 in CRC
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ملخص المشاركة:
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From our previous line of findings, CCL5 is highly expressed after
induction of the SIP1 gene in DLD-SIP-1 cells, and in the mesenchymal CRC
cell lines expressing ZEB1/2. ZEB1/2 have been strongly implicated in CRC
metastasis and are associated with poor patient survival. Therefore, I have
proposed that CCL5 might be up-regulated upon induction of ZEB1/2 in
carcinoma cells making EMT and metastasis possible by escaping immune
destruction. Up to our knowledge there are only two recent reports linking
CCL5 up-regulation to EMT. However, none of them showed direct evidence that
ZEB1/2 up-regulate CCL5 expression. From the ChIP and luciferase findings, it
can be confidently concluded that SIP1 directly binds to the CCL5 promoter
activating gene transcription. This is an original and novel finding.
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المؤتمر (5):
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عنوان المؤتمر:
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9th Saudi students’ Conference (SSC2016)
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تاريخ الإنعقاد:
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13-14/02/2016
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مكان
الإنعقاد:
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Birmingham. UK
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طبيعة المشاركة:
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Poster Presentation
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عنوان المشاركة:
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The Molecular Basis of Immune Infiltration as a Result of a Metastatic
Program in CRC
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ملخص المشاركة:
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The presence of CCL5 in the serum of cancer patients or the expression
of CCL5 has been proposed as a negative prognostic marker. A key study also
identified CCL5 as a chemokine secreted by mesenchymal stem cells that are
recruited to primary breast cancers. The exposure of breast cancer cells to
CCL5 facilitated metastasis, but no mechanism e.g. whether CCL5 can induce
EMT or the immune-deficient microenvironment allowed cancer cells to escape
immunity and metastasize, has been identified. These results suggest that
CCL5 is necessary for metastasis. Our findings suggest that, in addition to
mesenchymal stem cells, CCL5 can also be abundantly secreted by cancer cells
undergoing EMT. In order to investigate whether CCL5 can induce EMT and
therefore metastasis or EMT-induced CCL5 expression can alter immune
infiltration in CRC to favour an immuno-deficient microenvironment; we
investigated the contribution of CCL5 in EMT and therefore metastasis by
generating a CCL5 over-expressing and CCL5 knockdown CRC cell lines, checking
its EMT properties, and performing in vivo experiments. Tumour micrroarray
showed that pateints with SIP1 high expression have as well high CCL5
expression and low density of T-infiltrating lymphocytes (TILs).
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جوائز التكريم:
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الجائزة (1):
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مسمى الجائزة:
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Third Prize
Winner.
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الجهة المانحة:
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Burden of
Cancer in the Gulf Region
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تاريخ الجائزة:
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23 October
2014
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مجال التكريم:
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SIP1 Induced
Epithelial Mesenchymal Transition Promotes Metastasis and Alters Tumour
Microenvironment by Modulating CCL5 Expression
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