ABSTRACT
Chondrosarcomas are malignant cartilage-forming bone tumors, which are intrinsically resistant to chemo- and radiotherapy, leaving surgical removal as the only curative treatment option. Therefore, our aim was to identify genes involved in chondrosarcoma cell survival that could serve as a target for therapy. siRNA screening for 51 apoptosis-related genes in JJ012 chondrosarcoma cells identified BIRC5, encoding survivin, as essential for chondrosarcoma survival. Using immunohistochemistry, nuclear as well as cytoplasmic survivin expression was analyzed in 207 chondrosarcomas of different subtypes. Nuclear survivin has been implicated in cell-cycle regulation while cytoplasmic localization is important for its anti-apoptotic function. RT-PCR was performed to determine expression of the most common survivin isoforms. Sensitivity to YM155, a survivin inhibitor currently in phase I/II clinical trial for other tumors, was examined in 10 chondrosarcoma cell lines using viability assay, apoptosis assay and cell-cycle analysis. Survivin expression was found in all chondrosarcoma patient samples. Higher expression of nuclear and cytoplasmic survivin was observed with increasing histological grade in central chondrosarcomas. Inhibition of survivin using YM155 showed that especially TP53 mutant cell lines were sensitive, but no caspase 3/7 or PARP cleavage was observed. Rather, YM155 treatment resulted in a block in S phase in two out of three chondrosarcoma cell lines, indicating that survivin is more involved in cell-cycle regulation than in apoptosis. Thus, survivin is important for chondrosarcoma survival and chondrosarcoma patients might benefit from survivin inhibition using YM155, for which TP53 mutational status can serve as a predictive biomarker.
ABSTRACT
A method was developed for isolation of aromatic polycyclic hydrocarbons (APH) from atmospheric air. Air samples were filtered through Whatman GF/C filter papers, subsequently extracted with benzene. Aromatic polycyclic hydrocarbons were isolated from the extract, purified by column chromatography on aluminium oxide and determined by gas chromatography. This method was applied to determine qualitatively and quantitatively: naphthalene, anthracene, pyrene, perilene, biphenyl, fluoranthene, phenanthrene, benzo(a)pyrene, dibenzo(a,c)anthracene, dibenzo(g,h)anthracene, 11H-benzo(a)fluorane, 11H-benzo(b)fliorene, benzo(g,h,i)perylene, benzo(a)anthracene, chrysene, indene and durene. Professional exposure in years 1977-1989 was comparatively assessed using the evaluation criterion for APH expressed as the benzene fraction (0.2 mg/m3--USA standard) and as benzo(a)pyrene (0.00015 mg/m3--USSR standard). According to the accepted standards, working conditions in the examined plants entail a risk for the employees. Comparison of the results obtained before and after reconditioning of the machinery suggests the need for further modernization aimed at application of new technical solutions allowing for limitation of pollutant emission to air.
