Publications by authors named "Alice Pezzoni"

2 Publications

  • Page 1 of 1

The Polo-Like Kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia.

PLoS One 2013 8;8(3):e58424. Epub 2013 Mar 8.

Oncology, Nerviano Medical Sciences, Nerviano, Milano, Italy.

CD56 is expressed in 15-20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56(+) monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MSTβ€Š=β€Š28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56(+) AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058424PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592825PMC
September 2013

Phosphorylation of TCTP as a marker for polo-like kinase-1 activity in vivo.

Anticancer Res 2010 Dec;30(12):4973-85

BU Oncology, Nerviano Medical Sciences srl, 20014 Nerviano, Italy.

Polo-like kinase 1 (PLK1) is the master regulator of mitosis and a target for anticancer therapy. To develop a marker of PLK1 activity in cells and tumour tissues, this study focused on translational controlled tumour protein (TCTP) and identified serine 46 as a site phosphorylated by PLK1 in vitro. Using an antibody raised against phospho-TCTP-Ser46, it was demonstrated that phosphorylation at this site correlates with PLK1 level and kinase activity in cells. Moreover, PLK1 depletion by siRNA or inactivation by specific inhibitors caused a correspondent decrease in phospho-TCTP-Ser46 signal validating this site as a direct marker of PLK1. Using this marker, the study characterized PLK1 inhibitors in cells by setting up a high-content assay and finally immunohistochemical assay suitable for following inhibitor activity in preclinical tumour models and possibly in clinical studies was developed.
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December 2010