<div dir="ltr"><div><p class="MsoNormal" align="center" style="text-align:center"><b><span style="font-size:22pt;font-family:'Times New Roman',serif">Colloqui della Classe di Scienze</span></b></p>

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<p class="MsoNormal" align="center" style="margin-left:9pt;text-align:center;line-height:18pt"><span style="font-size:16pt;font-family:'Times New Roman',serif">Mercoledì 8 giugno 2016 <br>
ore 15:00 </span><u><span style="font-size:16pt;font-family:'Times New Roman',serif"></span></u></p>

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<p class="MsoNormal" align="center" style="margin-left:9pt;text-align:center;line-height:18pt"><u><span style="font-size:16pt;font-family:'Times New Roman',serif">Scuola Normale Superiore</span></u></p>

<p class="MsoNormal" align="center" style="margin-left:9pt;text-align:center;line-height:18pt"><span style="font-size:16pt;font-family:'Times New Roman',serif">Pisa</span></p>

<p class="MsoNormal" align="center" style="margin-left:9pt;text-align:center;line-height:18pt"><span style="font-size:16pt;font-family:'Times New Roman',serif">(Sala Azzurra)</span></p>

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<p class="MsoNormal" align="center" style="text-align:center;background-image:initial;background-repeat:initial"><span style="font-family:Arial,sans-serif"><br>
</span><b><span style="font-size:24pt;font-family:'Times New Roman',serif">Prof. </span></b><b><span style="font-size:24pt;font-family:Arial,sans-serif"> </span></b><b><span style="font-size:24pt;font-family:'Times New Roman',serif">Pier Giuseppe Pelicci</span></b><span style="font-size:24pt;font-family:'Times New Roman',serif"></span></p>

<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><i><span style="font-family:'Times New Roman',serif">((</span></i><i><span style="font-family:'Times New Roman',serif">Istituto Europeo di Oncologia
(IEO), Milan, Italy – </span></i></p>

<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><i><span lang="EN-US" style="font-family:'Times New Roman',serif">Department of Oncology and Haemato-oncology,
University of Milan, Italy)</span></i></p>

<p class="MsoNormal"><i><span lang="EN-US" style="font-family:'Times New Roman',serif"> </span></i></p>

<p class="MsoNormal" align="center" style="text-align:center"><span style="font-size:16pt;font-family:'Times New Roman',serif">Terrà un
seminario dal titolo:</span></p>

<p class="MsoNormal"><b><i><span style="font-size:11pt;font-family:'Times New Roman',serif"> </span></i></b></p>

<p class="MsoNormal" align="center" style="text-align:center;background-image:initial;background-repeat:initial"><b><span lang="EN-US" style="font-size:22pt;font-family:'Times New Roman',serif;background-image:initial;background-repeat:initial">“</span></b><b><span lang="EN-US" style="font-size:22pt;font-family:'Times New Roman',serif">Regulation of
self-renewal in cancer stem cells</span></b><b><span lang="EN-US" style="font-size:22pt;font-family:'Times New Roman',serif;background-image:initial;background-repeat:initial">”</span></b></p>

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<p class="MsoNormal" style="background-image:initial;background-repeat:initial"><b><span lang="EN-US" style="font-family:'Times New Roman',serif;background-image:initial;background-repeat:initial">Abstract:</span></b></p>

<p class="MsoNormal" style="text-align:justify"><font face="arial, helvetica, sans-serif"><i><span lang="EN-US">“</span></i><i><span lang="EN-US">Recent findings support the concept that cells with
the properties of stem cells (SC) are integral to the development and
perpetuation of several forms of human cancer, and that eradication of cancer
stem cells (CSC) may be essential to achieve cancer cure. However, direct proof
of these concepts is still lacking, mainly due the scarcity of appropriate
model systems.<span style="color:black"> We have recently </span>defined a
number of CSC-specific biological properties and underlying molecular
mechanisms, using mouse models of i) leukaemia, obtained by transgenic
expression of the PML-RAR, mutant NPM or AML1-ETO leukemia-associated
oncogenes; and ii) mammary tumor, obtained by transgenic expression of the
ErbB2 oncogene. We found that self-renewing divisions of CSCs are more frequent
than normal counterparts, unlimited and symmetric, thus contributing to
increasing numbers of SCs in tumoral tissues. SCs with targeted mutation of the
tumor suppressor p53 possess the same self-renewal properties of cancer SCs,
and their number increases progressively in the p53-null pre-malignant mammary
gland. We showed that p53 signaling is attenuated in ErbB2-driven tumors, and
that pharmacological re-activation of p53 induced restoration of asymmetric
divisions in cancer SCs and tumor growth reduction, without affecting rates of
apoptosis or proliferation on additional cancer cells. These data demonstrate
that p53 regulates polarity of cell division in mammary SCs and suggest that
loss-of-p53 in epithelial cancers favors symmetric divisions of CSCs,
contributing to tumor growth. As a further mechanisms of extended self-renewal
in cancer stem cells, we have demonstrated that up-regulation of the cell-cycle
inhibitor p21 is indispensable for maintaining self-renewal of leukaemia SCs
(LSCs). Expression of leukaemia-associated oncogenes in normal hematopoietic
SCs (HSCs) induces DNA damage and activates a p21-dependent cellular response that,
in turn, imposes cell-cycle restriction and triggers repair of the damaged DNA.
This effect of p21 prevents the physiological exhaustion of HSC self-renewal,
which occurs in time owing to accumulation of DNA damage, and confers an
advantage to HSCs when they hyper-proliferate, as it occurs during stress or
after full transformation (for example, in the LSCs), thus explaining the role
of p21 in the maintenance of the self-renewal potential of LSCs. Finally, I
will discuss unpublished data showing the contribution of immune-surveillance
to the elimination of DNA-damaged SCs, and the underlying role of p21.”<span style="color:black"></span></span></i></font></p>

<p class="MsoNormal" style="text-align:justify"><i><span lang="EN-US" style="font-family:'Times New Roman',serif"> </span></i></p>

<p class="MsoNormal" style="text-align:justify"><span lang="EN-US" style="font-size:16pt;font-family:'Times New Roman',serif"> </span></p>

<p class="MsoNormal" style="text-align:justify"><span style="font-size:16pt;font-family:'Times New Roman',serif">Tutti gli interessati sono invitati a
partecipare.</span></p>

<p class="MsoNormal" style="text-align:justify"><span style="font-size:16pt;font-family:'Times New Roman',serif"> </span></p>

<p class="MsoNormal" style="text-align:justify"><span style="font-size:16pt;font-family:'Times New Roman',serif">Classe di Scienze Matematiche e Naturali</span></p></div><div><br></div><br clear="all"><div><div class="gmail_signature" data-smartmail="gmail_signature"><div dir="ltr"><div>Valeria Giuliani</div><div>Scuola Normale Superiore</div><div>Servizio alla Didattica e Allievi</div><div>tel. 050 509260</div><div>Piazza dei Cavalieri, 7</div><div>56126 Pisa</div><div>E-mail: <a href="mailto:valeria.giuliani@sns.it" target="_blank">valeria.giuliani@sns.it</a></div><div>E-mail: <a href="mailto:classi@sns.it" target="_blank">classi@sns.it</a></div></div></div></div>
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