Jean Paul II Research Foundation

Campobasso, Italy

Jean Paul II Research Foundation

Campobasso, Italy
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Persico M.,University of Naples Federico II | Petrella L.,Jean Paul II Research Foundation | Orteca N.,University of Naples Federico II | Di Dato A.,University of Naples Federico II | And 7 more authors.
European Journal of Medicinal Chemistry | Year: 2014

GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel. © 2014 Elsevier Masson SAS.


Persico M.,University of Naples Federico II | Petrella L.,Jean Paul II Research Foundation | Orteca N.,University of Naples Federico II | Di Dato A.,University of Naples Federico II | And 7 more authors.
European Journal of Medicinal Chemistry | Year: 2015

GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel. © 2014 Elsevier Masson SAS.


Raspaglio G.,Catholic University of the Sacred Heart | Petrillo M.,Catholic University of the Sacred Heart | Martinelli E.,Catholic University of the Sacred Heart | Li Puma D.D.,Catholic University of the Sacred Heart | And 10 more authors.
Gene | Year: 2014

SOX9 [(sex determining region Y)-box9] gene has been implicated in the development and progression of different neoplasms. This study investigated the role of Sox9 in the expression of TUBB3 gene, a marker of aggressiveness in ovarian cancer (OC), encoding βIII-tubulin protein. Gene expression was assessed by quantitative polymerase chain reaction (qPCR) in OC models.Using chromatin immunoprecipitation (ChIP) we found that Sox9 engages TUBB3 promoter at minus 980 base pairs from the transcriptional start site with transcriptional enhancing effects. Furthermore we found that Sox9 is a downstream target of Hif-2α, a transcription factor encoded by endothelial PAS domain protein-1 (EPAS1). Hypoxic microenvironment is a common feature of solid tumors associated with cancer aggressiveness. In the present work we found that knockdown of either SOX9 or EPAS1 abolished TUBB3 gene induction in hypoxia. This phenomenon was associated with a decrease in the number of cell colonies capable of growing in an anchorage-independent way. Using a nanofluidic genetic analyzer, the expression of SOX9, TUBB3 and EPAS1 was evaluated in 182 OC specimens. Double staining immunohistochemistry was employed to evaluate the expression and prognostic role of both Sox9 and βIII-tubulin. Results obtained in cellular models matched the pattern of clinical specimens. We documented a direct correlation among the expression of EPAS1, SOX9 and TUBB3 at mRNA level. Patients displaying no expression for the three genes had the best outcome. A poor prognosis significant in multivariate analysis was visible in patients featuring high expression of βIII-tubulin and nuclear Sox9. Conclusions: Sox9 allows the survival of OC cells upon hypoxic condition, through the activation of βIII-tubulin expression and its aberrant activation in OC is prominent in patients with aggressive OC. © 2014 Elsevier B.V.

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