Noteworthy, our experimental model needed i.p. injections of BSc2118 that might not induce satisfactory level of proteasome inhibition and had no effects on tumor growth. However, in this application design there was a tendency at the border of significance to reduce the number of metastases and De Novo arising blood vessels. It seems that BSc2118 retards tumor growth by means of 20S inhibition within tumor cells and additionally might reduce both

PD98059 metastasis and angiogenesis. In conclusion, we characterized a novel proteasome inhibitor that has a similar proteasome inhibition spectrum compared to bortezomib In Vitro and In Vivo, but has under the conditions tested less signs of toxicity. We hypothesize that BSc2118 is a therapeutic alternative to bortezomib in therapy of solid tumors, for which further studies will be needed. The following are the supplementary data related to this click here article. Supplementary Figure 1.   Inhibition of tissue-derived proteasomes In Vitro. 20S proteasomes were isolated from indicated mouse organs and incubated with indicated concentrations of BSc2118. A final concentration of 50 nM of BSc2118 is sufficient to reduce 40% to 50% of initial 20S activity. *Significantly different from controls (*P < 0.05 and **P < 0.005). This work

was in part supported by the Polish Ministry of Science and higher Education (grant number: N405 007 31/0544 to IMB). We thank Dr. Anna Ratajska from the Department of Pathological Anatomy, Medical University of Warsaw, Poland, for assistance in preliminary experiments on BSc2118-FL stability in mice. “
“Wilms’ tumor gene WT1 is located on chromosome 11q13 and it encodes a zinc finger transcription factor [1]. The WT1 protein activates or represses the transcription of many target genes involved in the cell cycle, proliferation, differentiation, and apoptosis [2], [3] and [4]. WT1 was initially identified as a tumor suppressor gene due to its inactivation

in Wilms’ tumor (nephroblastoma), the most common pediatric kidney tumor [5]. However, recent findings have shown that WT1 Megestrol Acetate acts as an oncogene in some cancers, including ovarian cancer [6], [7], [8], [9], [10] and [11]. Previous studies have demonstrated that high expression levels of WT1 correlate with poor prognosis in leukemia [12] and breast cancer [13] and with more advanced tumor stages in testicular germ cell tumors [14] and head and neck squamous cell carcinoma [15]. In ovarian cancer, WT1 is highly expressed in high-grade serous carcinoma, a more aggressive subtype [16]. Moreover, our unpublished data demonstrated that high levels of WT1 expression yielded tumors with more aggressive International Federation of Gynecology and Obstetrics (FIGO) stages, lymph node metastasis status, omentum metastasis status, and ascites production in ovarian cancers.