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Conticello C.,Mediterranean Institute of Oncology IOM | Giuffrida R.,IOM Mediterranean Institute of Oncology Ricerca | Adamo L.,IOM Mediterranean Institute of Oncology Ricerca | Anastasi G.,IOM Mediterranean Institute of Oncology Ricerca | And 12 more authors.
Leukemia Research | Year: 2011

Several reports demonstrated that the activation of Nuclear Factor-kappa B NF-κB is essential for the pathogenesis of multiple myeloma (MM). We analyzed the nuclear localization of NF-κB in MM-cells derived from 60 different patients with MM at presentation and in relapse, as well as in three myeloma cell lines. Nuclear localization (the active form) of NF-κB was detected in only one MM-sample from a refractory patient and in two samples from relapsed patients, while all the other samples, including the MM-cell lines, almost exclusively express the cytoplasmic (inactive) form of NF-κB. In mesenchymal cells from MM-patients NF-κB was clearly present in the nucleus. In addition, the proteasome inhibitor Bortezomib, which is described to antagonize NF-κB activity, had a consistent antitumor activity against both chemoresistant and chemosensitive MM-cells, regardless the NF-κB localization, thus suggesting the existence of other molecular targets of proteasome inhibitors in MM. © 2010 Elsevier Ltd.


Conticello C.,Mediterranean Institute of Oncology IOM | Giuffrida R.,IOM Mediterranean Institute of Oncology Ricerca | Parrinello N.,University of Catania | Buccheri S.,IOM Mediterranean Institute of Oncology Ricerca | And 10 more authors.
Leukemia Research | Year: 2013

CD200 is a relatively ubiquitously expressed molecule that plays a role in cancer immune evasion through interaction with its receptors. High expression levels of CD200 have been described in different human malignancies. For example, CD200 has been shown to be targeted after RAS/RAF/MEK/ERK activation in melanoma. Here we present the analysis of CD200 expression in human Multiple Myeloma (MM) samples. We found that CD200-positive cells express ERK and p-ERK. Moreover, UO126, a MEK inhibitor, reduces CD200 expression. Furthermore, we observe that CD200-positive cells show reduced immunogenicity compared to normal lymphocytes and that such immunogenicity increases when UO126 is used. We therefore hypothesize that CD200 expression in MM could suppress antitumor response and that anti-CD200 treatment might be therapeutically beneficial in CD200-expressing tumors. © 2013 Elsevier Ltd.

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