البحوث المنشورة
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البحث (1): كتاب
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عنوان الكتاب:
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Next Generation Sequencing in Cancer
Research
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رابط الوصول:
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Link
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تاريخ النشر:
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2013
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موجز عن البحث:
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This book is to introduce state-of-the-art Next
Generation Sequencing (NGS) technologies for cancer genome research and to
show a broad audience, including cancer biologists and oncologists, the
technology revolution that is occurring in high- throughput DNA sequencing
and the paradigm shifts that it is causing in the cancer research community.
Following the discovery of the
double-stranded structure of DNA, different methods to read the nucleotide
sequence of DNA placed important milestones in the life sciences and changed
the direction of biomedical research, including cancer.
Prior to 2005, DNA sequencing relied on the
Maxam-Gilbert and the Sanger dideoxy- chain-termination methods. They are
considered to be fi rst-generation sequencing technology, but they played a
historic role in the decade-long, multibillion- dollar human genome project
that was completed in 2003. The demand grew for new technologies to deliver
faster, cost-effective, and more accurate genomic information from the
complexity of gene regulatory networks in normal and diseased cells. The
effort led to the development of next-generation sequencing technologies and
the production of massive amounts of sequencing data compared to conventional
methods. There has been an astonishing tenfold decline in the cost for
sequencing per year, which far outpaces Moore’s Law. Numerous commercialized
technologies, including Roche/454, ABI/SoLiD, Illumina/Solexa, Helicos, and
Pacifi c Biosciences, have been widely used for diverse applications ranging
from biology to medicine and extending to agriculture and fundamental
research in evolution.
Cancer is a complex genetic disease and,
during the last half-century, we have made great progress in understanding
the mechanism of cancer initiation, development, and metastasis at the
cellular and molecular levels. As a result, targeted therapy has indeed improved treatment for certain
cancers using drugs such as Gleevec (imatinib mesylate) for chronic
myelogenous leukaemia, Erlotinib for non-smallcell lung cancer with EGFR
mutation, Herceptin (trastuzumab) for a subset of breast cancer with HER2/neu
gene amplifi cation, and recent BRAF inhibitors for metastatic melanoma.
Scientists around the world are attempting to
fi nd the root causes of cancer and they are looking for more direct and
effective means to cure cancer. This journey to conquer cancer is more
optimistic now with the unfolding of the cancer genome.
The cancer genome project was initiated a few
years after the completion of human genome project and, through the use of
high-throughput mutation detection techniques, it aimed to identify
somatically acquired sequence variants and mutations and, hence, to identify
the genes that are critical in the development of human cancers.
Subsequently, the international cancer genome
consortium (ICGC) was developed to depict all the mutations, including copy
number changes, insertions and deletions, in 50 types of cancers. To date,
numerous cancer genomes have been sequenced, which are helping us to gain an
unprecedented understanding of molecular mechanisms underlying the complexity
of cancer biology. The translation of cancer genome sequencing is starting to
guide diagnosis and effective treatment.
The cancer initiatome is the collection of
all causes of malignant transformation; it extends beyond the ~2 % protein-coding
content of the genome and resides in the non-coding RNA molecules (e.g.,
piRNAs, microRNAs, long non-coding RNAs) in the actively transcribed regions
of the genome. Unravelling the complexity of the cancer initiatome is
revealing new players in cancer cells and providing contemporary challenges
in a new era of cancer research.
The cancer genome research that has emerged
so far from advances in NGS technology is thrilling. It is imperative to
bring this frontier research to graduate students, postdoctoral fellows, and
junior scientists in basic and translational cancer research. We invited
scientists who carry out their research with NGS technology to share their
experience, enthusiasm, and passion for research on the cancer genome.
The authors present the principles of NGS
technologies and massively parallel DNA sequencing and their application of
the whole genome sequences (WGS), exome-seq, RNA-seq, miRNA-seq, and ChIP-seq
in their research programs.
Moreover, the authors discuss their
experimental designs and the analysis of their biological data with the
latest bioinformatics tools. NGS produces a massive amount of data, and the
challenge of managing the data is beyond the scope of this book;
nevertheless, the basic concepts of computational analyses are well covered.
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البحث (2):
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عنوان البحث:
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Epigenetic regulation of microRNA expression
in cancer
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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2011
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موجز عن البحث:
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Epigenetic gene regulation is important in human cancer. Both
functional and observational data implicate alterations of histone
modifications, DNA promoter methylation, and non-coding RNA expression in
carcinogenic roles. We sought to explore the role of aberrant DNA
hypermethylation in the regulation of microRNA (miR) expression in human
cancer. From human genome databases we calculated that 13 and 28% of human
miR genes are located within 3 and 10 kb of a CpG island, respectively. To
identify miRs that are regulated by epigenetic mechanisms in cancer, we
performed expression profiling prior to and following treatment of cell lines
with 5-azacytidine. We used oligonucleotide microarrays to determine miR
expression. For miRs whose expression changed following 5-azacytidine
treatment, we sequenced the adjacent CpG island and promoter using
bisulphite-treated DNA. Here, we describe these methods to enable other
researchers to use this approach.
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البحث (3):
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عنوان البحث:
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Tumor hypoxia induces nuclear
paraspeckle formation through HIF-2α dependent transcriptional activation of
NEAT1 leading to cancer cell survival
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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24/11/2014
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موجز عن البحث:
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Activation of cellular transcriptional
responses, mediated by hypoxia-inducible factor (HIF), is common in many
types of cancer, and generally confers a poor prognosis. Known to induce many
hundreds of protein-coding genes, HIF has also recently been shown to be a
key regulator of the non-coding transcriptional response. Here, we show that
NEAT1 long non-coding RNA (lncRNA) is a direct transcriptional target of HIF
in many breast cancer cell lines and in solid tumors. Unlike previously
described lncRNAs, NEAT1 is regulated principally by HIF-2 rather than by
HIF-1. NEAT1 is a nuclear lncRNA that is an essential structural component of
paraspeckles and the hypoxic induction of NEAT1 induces paraspeckle formation
in a manner that is dependent upon both NEAT1 and on HIF-2. Paraspeckles are
multifunction nuclear structures that sequester transcriptionally active
proteins as well as RNA transcripts that have been subjected to
adenosine-to-inosine (A-to-I) editing. We show that the nuclear retention of
one such transcript, F11R (also known as junctional adhesion molecule 1,
JAM1), in hypoxia is dependent upon the hypoxic increase in NEAT1, thereby
conferring a novel mechanism of HIF-dependent gene regulation. Induction of
NEAT1 in hypoxia also leads to accelerated cellular proliferation, improved
clonogenic survival and reduced apoptosis, all of which are hallmarks of
increased tumorigenesis. Furthermore, in patients with breast cancer, high
tumor NEAT1 expression correlates with poor survival. Taken together, these results
indicate a new role for HIF transcriptional pathways in the regulation of
nuclear structure and that this contributes to the pro-tumorigenic
hypoxia-phenotype in breast cancer.
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البحث (4):
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عنوان البحث:
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Hypoxic regulation of the noncoding
genome and NEAT1
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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20/11/2015
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موجز عن البحث:
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Activation
of hypoxia pathways is both associated with and contributes to an aggressive
phenotype across multiple types of solid cancers. The regulation of gene
transcription by hypoxia-inducible factor (HIF) is a key element in this
response. HIF directly upregulates the expression of many hundreds of
protein-coding genes, which act to both improve oxygen delivery and to reduce
oxygen demand. However, it is now becoming apparent that many classes of
noncoding RNAs are also regulated by hypoxia, with several (e.g. micro RNAs,
long noncoding RNAs and antisense RNAs) under direct transcriptional
regulation by HIF. These hypoxia-regulated, noncoding RNAs may act as
effectors of the indirect response to HIF by acting on specific coding
transcripts or by affecting generic RNA-processing pathways. In addition,
noncoding RNAs may also act as modulators of the HIF pathway, either by
integrating other physiological responses or, in the case of HIF-regulated,
noncoding RNAs, by providing negative or positive feedback and feedforward
loops that affect upstream or downstream components of the HIF cascade. These
hypoxia-regulated, noncoding transcripts play important roles in the
aggressive hypoxic phenotype observed in cancer.
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البحث (5): كتاب
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عنوان البحث:
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Next
Generation Sequencing in Cancer Research, Volume 2 From Basepairs to Bedsides
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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2015
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موجز عن البحث:
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Latest generation sequencing
revolutionizes the fields of cancer research and oncology. This follow-up
volume focuses more extensively on single cell sequencing of cancer and
trials in drug resistance. Another exciting feature is the bioinformatics
tools given, that can be used on cancer genome studies. Scientists around the
world are attempting to find the root cause of cancer. A reasonable cancer
treatment plan and potential cure is more optimistic now with the unfolding
of the cancer genome. The collective knowledge of how to leverage next
generation sequencing in cancer research is paving the way. The important
information provided in this volume will move the field forward in developing
novel targeted cancer therapies.
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البحث (6):
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عنوان البحث:
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The tumour hypoxia induced non-coding
transcriptome
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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21/01/2016
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موجز عن البحث:
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Recent investigations have highlighted
the importance of the non-coding genome in regions of hypoxia in tumours.
Such regions are frequently found in solid tumours, and are associated with
worse patient survival and therapy resistance. Hypoxia stabilises the
transcription factors, hypoxia inducible factors (HIF1α and HIF2α) which
coordinate transcriptomic changes that occur in hypoxia. The changes in gene
expression induced by HIF1α and HIF2α contribute to many of the hallmarks of
cancer phenotypes and enable tumour growth, survival and invasion in the
hypoxic tumour microenvironment. Non-coding RNAs, in particular microRNAs
(miRNAs), which regulate mRNA stability and translation, and long-non-coding
RNAs (lncRNAs), which have diverse functions including chromatin modification
and transcriptional regulation, are also important in enabling the key
hypoxia regulated processes. They have roles in the regulation of metabolism,
angiogenesis, autophagy, invasion and metastasis in the hypoxic microenvironment.
Furthermore, HIF1α and HIF2α expression and stabilisation are also regulated
by both miRNAs and lncRNAs. Here we review the recent developments in the
expression, regulation and functions of miRNAs, lncRNAs and other non-coding
RNA classes in tumour hypoxia.
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البحث (7):
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عنوان البحث:
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Current
Management Strategies in Breast Cancer by Targeting Key Altered Molecular
Players
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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01/03/2016
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موجز عن البحث:
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Breast cancer is the second largest
disease affecting women worldwide. It remains the most frequently reported
and leading cause of death among women in both developed and developing
countries. Tamoxifen and raloxifene are commonly used selective estrogen
receptor modulators for treatment of breast cancer in women with high risk,
although resistance occurs by tamoxifen after 5 years of therapy and both
drugs cause uterine cancer and thromboembolic events. Aromatase inhibitors
(AIs) are one of the optional modes used for breast cancer treatment. The
combination of AIs along with tamoxifen can also be beneficial. Various
therapeutic agents from different sources are being studied, which further
need to be improved for potential outcome. For this, clinical trials based on
large number of patients with optimal dose and lesser side effects have to be
more in practice. Despite the clinical trials going on, there is need of
better molecular models, which can identify high risk population, new agents
with better benefit having less side effects, and improved biomarkers for
treating breast cancer.
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البحث (8):
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عنوان البحث:
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Role
of hesperetin in LDL-receptor expression in hepatoma HepG2 cells
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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27/06/2016
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موجز عن البحث:
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Background
High plasma concentration of
low-density lipoprotein cholesterol (LDL-c) plays a significant role in the
incidence of atherosclerosis and coronary heart diseases. The aim of this
study was to investigate the mechanism by which the citrus flavonoid,
hesperetin, regulates the LDL receptor (LDLr) gene in the human liver using
the human hepatoma cell line, HepG2.
Methods
Luciferase reporter gene assays were
performed (in the absence of lipoprotein) to measure the activity of the LDLr
promoter and the promoters of the sterol regulatory element binding protein (SREBP)
transcription factors that control the LDLr promoter.
Results
Only SREBP-1 promoter activity was
significantly increased 4 h after exposure to 200 μM hesperetin. However,
after 24 h incubation with 200 μM hesperetin, the activities of all the promoter-constructs,
SREBP-1a, -1c, -2 and LDLr, were significantly increased. The effects of 200
μM hesperetin on elevating LDLr mRNA levels were possibly due to regulation
of LDLr gene transcription by SREBP-la and SREBP-2.
Conclusions
We conclude that 200 μM hesperetin was
likely to have stimulated LDLr gene expression in human hepatoma HepG2 cells
via increased phosphorylation of PI3K andERK1/2, which increased SREBP-1a and
SREBP-2 mRNA levels and enhanced the maturation of the encoded proteins. This
may lead to lower plasma LDL cholesterol; therefore, diets supplemented with
hesperidin might provide cardio-protective effects and reduce mortality and
morbidity from coronary heart diseases.
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البحث (9):
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عنوان البحث:
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Weighted gene co-expression network
analysis of colorectal cancer liver metastasis genome sequencing data and
screening of anti-metastasis drugs
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رابط إلى البحث:
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Click here
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تاريخ النشر:
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30/06/2016
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موجز عن البحث:
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Approximately 9% of cancer-related
deaths are caused by colorectal cancer (CRC). CRC patients are prone to liver
metastasis, which is the most important cause for the high CRC mortality
rate. Understanding the molecular mechanism of CRC liver metastasis could
help us to find novel targets for the effective treatment of this deadly
disease. Using weighted gene co-expression network analysis on the sequencing
data of CRC with and with metastasis, we identified 5 colorectal cancer liver
metastasis related modules which were labeled as brown, blue, grey, yellow
and turquoise. In the brown module, which represents the metastatic tumor in
the liver, gene ontology (GO) analysis revealed functions including the
G-protein coupled receptor protein signaling pathway, epithelial cell
differentiation and cell surface receptor linked signal transduction. In the
blue module, which represents the primary CRC that has metastasized, GO
analysis showed that the genes were mainly enriched in GO terms including
G-protein coupled receptor protein signaling pathway, cell surface receptor
linked signal transduction, and negative regulation of cell differentiation.
In the yellow and turquoise modules, which represent the primary
non-metastatic CRC, 13 downregulated CRC liver metastasis-related candidate
miRNAs were identified (e.g. hsa-miR-204, hsa-miR-455, etc.). Furthermore,
analyzing the DrugBank database and mining the literature identified 25 and
12 candidate drugs that could potentially block the metastatic processes of
the primary tumor and inhibit the progression of metastatic tumors in the
liver, respectively. Data generated from this study not only furthers our
understanding of the genetic alterations that drive the metastatic process,
but also guides the development of molecular-targeted therapy of colorectal
cancer liver metastasis.
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البحث (10):
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عنوان البحث:
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Capture-C reveals preformed chromatin
interactions between HIF-binding sites and distant promoters
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رابط إلى البحث:
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Click
here
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تاريخ النشر:
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08/08/2016
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موجز عن البحث:
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Hypoxia‐inducible factor (HIF) directs an extensive
transcriptional cascade that transduces numerous adaptive responses to
hypoxia. Pan‐genomic
analyses, using chromatin immunoprecipitation and transcript profiling, have
revealed large numbers of HIF‐binding sites that are generally associated
with hypoxia‐inducible
transcripts, even over long chromosomal distances. However, these studies do
not define the specific targets of HIF‐binding sites and do not reveal how induction
of HIF affects chromatin conformation over distantly connected functional
elements. To address these questions, we deployed a recently developed
chromosome conformation assay that enables simultaneous high‐resolution analyses from multiple
viewpoints. These assays defined specific long‐range interactions between intergenic HIF‐binding regions and one or more
promoters of hypoxia‐inducible
genes, revealing the existence of multiple enhancer–promoter,
promoter–enhancer, and enhancer–enhancer interactions. However, neither short‐term activation of HIF by hypoxia, nor
long‐term
stabilization of HIF in von Hippel–Lindau
(VHL)‐defective
cells greatly alters these interactions, indicating that at least under these
conditions, HIF can operate on preexisting patterns of chromatin–chromatin
interactions that define potential transcriptional targets and permit rapid
gene activation by hypoxic stress.
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جوائز التكريم:
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الجائزة (1):
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مسمى الجائزة:
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The
Best Paper Award
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الجهة المانحة:
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6th Saudi
Scientific International Conference Committee
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تاريخ منح الجائزة:
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11-14 October 2012
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مجال التكريم:
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Best
Paper: “ Functional Genomic profiling of Hypoxic Breast Cancer:search for
novel molecular biomarkers markers”
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الجائزة (2):
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مسمى الجائزة:
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NCRI
Prize Award
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الجهة المانحة:
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National
Cancer Research Institute
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تاريخ منح الجائزة:
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14 August 2013
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مجال التكريم:
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A
bursary of up to £250.00 towards expenses to attend the NCRI Cancer
Conference
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الجائزة (3):
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مسمى الجائزة:
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The ASHG/Charles J. Epstein Trainee
Award for Excellence in Human Genetics Research
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الجهة المانحة:
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The
American Society of Human Genetics
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تاريخ منح الجائزة:
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26/10/2013
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مجال التكريم:
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Predoctoral Semi-finalist
for the ASHG/Charles J. Epstein Trainee Award for Excellence in Human
Genetics Research
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الجائزة (4):
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مسمى الجائزة:
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The Graduate Research Prize
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الجهة المانحة:
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University of Oxford
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تاريخ منح الجائزة:
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2014
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مجال التكريم:
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Best Postgraduate student
in the Nuffield Department of Medicine at the University of Oxford
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الرابط:
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Click here
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الجائزة (5):
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مسمى الجائزة:
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Proffered Paper Award for Non-coding
RNA in cancers
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الجهة المانحة:
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European Association for Cancer
Research
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تاريخ منح الجائزة:
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05-08/07/2014
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مجال التكريم:
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Best paper on non-coding
RNA research in 23rd Biennial European Association for Cancer Research
Congress
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الجائزة (6):
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مسمى الجائزة:
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The Susan G. Komen Scholarship Winner
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الجهة المانحة:
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Susan G. Komen for the Cure Foundation
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تاريخ منح الجائزة:
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05-08/07/2014
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مجال التكريم:
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Best paper related to
breast cancer research in 23rd Biennial European Association for Cancer
Research Congress
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الجائزة (7):
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مسمى الجائزة:
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2014 American Association for Cancer Research
Scholar-in-Training Award
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الجهة المانحة:
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American Association for Cancer
Research (AACR)
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تاريخ منح الجائزة:
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09-13/12/2014
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مجال التكريم:
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Best paper presented in the
San Antonio Breast Cancer Annual Symposium 2014 (SABCS), USA
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الجائزة (8):
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مسمى الجائزة:
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2016 Professional Achievement Award – Education UK Alumni
Awards 2016
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الجهة المانحة:
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The British Council
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تاريخ منح الجائزة:
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2016
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مجال التكريم:
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Professional Achievement
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الرابط:
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Click
here
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