Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor

Purpose Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. Methods The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity. Results Good response to naCHT was noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders. Conclusion The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results

History trumps government unpopularity: the June 2003 Polish EU accession referendum

This analysis explains why Poles voted overwhelmingly to join the EU and how the 50% turnout requirement was achieved fairly easily. It argues that most Poles appeared to accept the historical significance of the referendum and de-coupled the issue of EU membership from that of confidence in an extremely unpopular government. This occurred because most key political and social actors, including the opposition parties, called for a Yes vote, while, at the same time, a vigorous campaign by pro-EU civic organisations presented a ‘non-political’ face to the campaign. Although the No camp made tactical errors and had difficulties staying focused on its main arguments, lack of both access to the public media and a convincing or attractive alternative made it extremely difficult for them to mount an effective campaign. At the same time, the stability of the opinion polls in the years leading up to the referendum suggested that most Poles had already made their minds up about the issue well in advance. In spite of the low levels of trust in political parties, partisan cues appeared to be a better predictor of referendum voting behaviour than socio-economic and demographic factors