[Todos] Seminarios conjuntos DFBMC-IFIByNE- Dr. Eduardo Farias

[Paula Felman]

>Seminario jueves 30 de Octubre. 13 hs. Aula del LFBM
>
>
>Eduardo F. Farias, Ph.D.
>Assistant Professor
>Mount Sinai School of Medicine
>Department of Medicine
>
>
>Oncogenes and Retinoid Chemoprevention
>
>Abstract
>Using transgenic mouse models relevant to human breast cancer (wnt1 and neu)
>crossed with RARa1 null, we found that RARs modulate tumor incidence in an
>oncogene-specific manner. The loss of RAR leads to an accelerated wnt1 and
>delayed neu tumor formation. These data predict that, depending on the
>oncogenic pathway, retinoid intervention might be either beneficial or
>detrimental. To test this prediction we compared the chemopreventive effects
>of RAR_-agonist, Am580, on MMTV-neu and MMTV-wnt1induced tumors. The
>expectation was that the Am580 treatment will reduce the number and size of
>MMTV-wnt1 tumors but increase the MMTV-neu induced tumors. As expected, we
>found that at 35 weeks of treatment the tumor incidence in the MMTV-wnt1
>group was reduced from 58% to 22%.  Unexpectedly, tumor incidence was also
>reduced from 85% in the control group to 58% in the AM580 treated group in
>the MMTV-neu mice. In both neu and wnt1 tumor growth rate was also affected
>by the AM580 treatment. Immunohistochemical and biochemical examination of
>the neu and wnt1 tumors revealed, in both cases, a reduction in markers
>associated with proliferation and an increase in markers related to
>apoptosis and differentiation; the effects were more evident in the wnt1
>tumors. Analysis of the ductal tree morphology in whole mounts of glands
>without palpable tumors revealed the presence of small lesions and tumors,
>and suggested a partial reversion of the oncogenic phenotype in both
>transgenic models. Finally, in vitro modeling in 3D cultures of the
>MMTV-wnt1 allowed us to reproduce the in vivo phenotype induced by the AM580
>treatment. Overall our data show an oncogene-dependent response to AM580
>with a moderate effect on the MMTV-neu induced tumors and a clear induction
>of differentiation in the MMTV-wnt1 induced tumors. This preclinical study
>tests the hypothesis that retinoids can be effective in a defined
>subpopulation of breast cancer. Our main objective is to generate data that
>will guide clinical trials in stratification of breast cancer patients for
>effective retinoid chemoprevention and treatment.
>
>__________ Información de NOD32, revisión 3548 (20081023) __________
>
>Este mensaje ha sido analizado con  NOD32 antivirus system
>http://www.nod32.com