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| Eleftheria
Panagiotou |
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Home
Institution
Albert-Ludwigs-Universität Freiburg
Host
Institution
Tufts University School of Medicine, Department of Cardiovascular Research,
St. Elizabeth's Medical Center, Boston
Mentor: Douglas W. Losordo, M.D.
E-Mail
Eleftheriapanagiotou@hotmail.com
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Research
Topic
see Abstract |
Personal
Reactions to the U.S. Experience
/ Greatest Difficulties Encountered
Being away from Europe for the first time in my life has certainly changed
my perception of what all Europeans have in common in terms of culture,
and what they are lacking compared to Americans. While encountering so many
different people during my stay here I missed the fact that, according to
our European standard, they don't share a common heritage deeply rooted
in history. On the other hand, being such a "young" nation and being relatively
"unburdened" by the past and its traditions could at least partly explain
the Americans' more uncomplicated way of dealing with problems and with
authorities in general. For instance, the traditional hierarchy I experienced
in labs or hospitals in Europe does not exist here, which makes the participation
both in research and in clinical work a lot easier and is more productive
in the end. I can strongly recommend this experience in the US to every
student, for even if I miss my own country(ies), the stay here has definitely
broadened both my personal horizon and my conception of what medicine is
and of how it should be carried out! |
Most
humorous incident
Please inform yourself how to use a simple lock in a locker here, for the
combination of numbers works in a very special way to open up the lock!
I didn't ask for advice the first time I used it and found myself hunting
on a Friday night for a person in the Tufts Gym to help me get my clothes
and my money out of the locker! |
Helpful
Hints for Future Students
1) Do not hesitate to ask other BMEP students for every kind of information
you would like to have concerning your stay here.
2) Don't worry, there is always a way to resolve whatever problem you might
encounter here! |
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Abstract
on Research Topic:
Taxol induces apoptosis of endothelial cells in vitro that can be reversed
after administration of VEGF |
Authors:
Rudolf Kirchmair, Eleftheria Panagiotou, Anne B. Tietz, Toshinori Murayama,
Andrea Wecker, Carole Amant, Douglas W. Losordo, Jeffrey M. Isner |
Institution
at which research was done:
Department of Cardiovascular Research, St Elizabeth's Medical Center, Boston,
MA |
Purpose:
The chemotherapeutic agent Taxol (Paclitaxel) is known for inducing a toxic
neuropathy in a high proportion of treated patients. Although higher doses
would be desirable in the treatment of some tumors, this side-effect is
often the dose-limiting factor in the cytostatic therapy. In addition to
its anti-mitotic activity, Taxol is a potent anti-angiogenic agent. Accordingly,
we hypothesized that the peripheral neuropathy could result from a destruction
of the nerve blood supply (vasa nervorum) and could therefore benefit from
angiogenic gene therapy with the endothelial mitogen vascular endothelial
growth factor (VEGF). My experiments in this study on the neuroprotective/regenerative
capabilities of angiogenic gene therapy focused on the effects of Taxol
on endothelial cells in vitro and their potential reversibility after administration
of VEGF. |
Materials
and Methods:
Human Umbilical Vein Endothelial Cells (HUVEC) were isolated, cultured in
6 or 24-well-plates and allowed to attach overnight. Cells in 6-well-plates
were starved in M199-Medium with1% BSA, treated with 0.02 M Taxol for 18
hours and processed for Western Blotting. 24-well-plates were starved in
M199-Medium with 2% BSA and treated with different concentrations of Taxol
for 48 hours, with or without adding 100 ng VEGF. In some other experiments,
cells were transfected with an adenovirus expressing Akt, and starved with
or without Taxol. After fixation of the HUVEC's by 1% PFA, apoptotic cells
were stained with DAPI, and examined by fluorescent microscopy. Total cell
number and apoptotic cells were counted. |
Results:
1) Taxol reduced cell-proliferation and increased the amount of apoptotic
cells in a dose-dependent manner. Addition of VEGF to Taxol-treated cells
significantly increased cell-proliferation and reduced the amount of apoptotic
cells.
2) Taxol-treated cells showed a decrease in the total and in the activated
(i.e. phosphorylated) form of the antiapoptotic protein Akt. After transfection
with an adenovirus expressing Akt, cell proliferation and apoptotic rate
in the endothelial cells were restored to normal.
3) Treatment of the endothelial cells with both Taxol and LY 294002, an
inhibitor to the PI3-Kinase/Akt-signal transduction pathway, resulted in
an increased rate of apoptosis as compared to the treatment with taxol alone.
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Conclusion:
Taxol decreases the proliferation and induces apoptosis of endothelial
cells in vitro due to inhibition of the anti-apoptotic Akt-pathway. The
latter is stressed by the fact that adenovirus-mediated overexpression
of Akt results in inhibiting the taxol-induced apoptosis. Co-incubation
of endothelial cells with taxol and VEGF also reduces apoptosis, thus
suggesting a beneficial effect of VEGF on Taxol-induced endothelial cell-death
in vivo.
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