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<!--StartFragment-->
<p class="MsoNormal" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">THE INFLUENCE OF HUMAN UMBILICAL VEIN
ENDOTHELIAL CELLS<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">IN THE FORMATION OF
GLIOBLASTOMA SPHEROIDS<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">IN </span></b><b><span style="font-family: 'Times New Roman'; ">THREE-DIMENSIONAL</span></b><b><span style="font-family: 'Times New Roman'; "> MICROWELLS</span></b><b><span style="font-family: 'Times New Roman'; "><o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-size: 14pt; font-family: 'Times New Roman'; "> </span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">Naze
Gul Avci<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; "> </span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">July
27<sup>th</sup> 2015<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">Smartboard Room #2013, SERC
Building<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">11:00 AM<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; "> </span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">Committee Chair: </span></b><span style="font-family: 'Times New Roman'; ">Dr.
Metin Akay<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><b><span style="font-family: 'Times New Roman'; ">Committee Members:<o:p></o:p></span></b></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><span style="font-family: 'Times New Roman'; ">Dr. Yasemin M Akay, </span><span style="font-family: 'Times New Roman'; ">Dr. David
Gorenstein,<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: center; "><span style="font-family: 'Times New Roman'; ">Dr. Ahmet
Omurtag, Dr. Ting Chen<o:p></o:p></span></p>
<p class="MsoNormal" style="font-size: 14px; font-family: Calibri, sans-serif; text-align: justify; "><span style="font-family: 'Times New Roman'; "> </span></p>
<p class="MsoNormal" style="text-align: center; "><b><font face="Times">ABSTRACT<o:p></o:p></font></b></p>
<p class="MsoNormal" style="text-align: justify; "><font face="Times">
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a high
infiltrative capacity and increased vascularity. Despite current therapies overall patient survival rate is
still poor. Therefore, alternative therapies have been considered for GBM
treatment such as oncolytic viruses.</font></p>
<p class="MsoNormal" style="text-align: justify; "><font face="Times">
The studies with two-dimensional (2D) cell cultures have been used as
physiological models for understanding the cellular and molecular behavior of
the GBM tumors. They are also highly desirable for virus studies. However they may not provide three-dimensional
(3D) characteristics of the tumors. Therefore,
there is an increasing need in 3D cell culture models to investigate cell
growth and cell-cell interactions. <o:p></o:p></font></p>
<p class="MsoNormal" style="text-align: justify; "><font face="Times">
In this thesis, we hypothesized that culturing GBM cells with endothelial cells
in the hydrogel microwells would mimic the <i>in vivo</i> microenvironment of
tumor cells. Thus, we could provide beneficial 3D <i>in vitro</i> co-culture models for GBM treatment with oncolytic
adenovirus, Delta-24-RGD ($B&$(B24RGD). Therefore, in the first part of this study, we used
our recently designed 3D PEGDA hydrogel microwell platform to co-culture GBM and HUVEC. We
investigated the gene expression differences to gain further insight into
molecular mechanism of 3D <i>in</i> <i>vitro</i> co-culture. Our gene
expression data suggested the relative up-regulation of tumor angiogenesis
markers; PECAM1/CD31 and VEGFR2 were consistent with <i>in vivo</i> GBM
studies. Finally, we treated GBM tumors using $B&$(B24RGD. <span style="color: rgb(49, 42, 42); ">The infection of the </span>$B&$(B24RGD was found more
effective on 3D spheroids than 2D monolayer cell culture. These results
implicated that our hydrogel microwell platform could contribute to mimic <i>in vivo</i>
microenvironment of the GBM tumors and provide a promising 3D model to
investigate the oncolytic potential of the viruses <i>in vitro</i>. </font><font face="Times New Roman" style="font-size: 14px; "><o:p></o:p></font></p>
<p class="MsoNormal" style="font-size: 14px; font-family: Calibri, sans-serif; "><span style="font-family: 'Times New Roman'; "> </span></p>
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