No abstract

The chromosomal translocation t(12;16)(q13;p11) is a common genetic alteration in myxoid and round-cell liposarcomas. It results in transcription of various chimeric FUS/CHOP fusion transcripts that encode different oncogenic proteins. Recent reports suggest that these may have different neoplastic transformation activities. To audit this hypothesis, we transfected expression plasmids for the two major variant FUS/ CHOP transcripts I and II in NIH 3T3 cells and determined the number of outgrowing foci as well as their growth potential in soft agar. In addition, we compared tumour growth in nude mice upon subcutaneous injection of the respective transfectants. No significant differences in transformation assays in vitro and in vivo were observed, suggesting that both variant transcripts confer comparable transforming activities. The histopathological picture of tumours derived from both cell populations resembles high-grade spindle cell sarcomas. This suggests that both FUS/CHOP variants cause similar patterns of differential gene expression. This hypothesis was confirmed by mRNA-expression profiles of the respective cell clones. Strong overexpression of the pentaxin-related gene (PTX), the osteoblast-specific factor 2 (osf-2), the basic Kruppel-like factor (bklf), the leucoprotease inhibitor, and the cyclophilin B were observed in both types of FUS/ CHOP-transfected cell clones. Taken together, our data suggest that different FUS/CHOP variants cause transformation of mesenchymal cells via the same pathways with comparable efficacy.

Bilateral neck exploration is the standard procedure of primary hyperparathyroidism. Preoperative localization is not mandatory. Intraoperative visualization methods help to avoid unsuccessful explorations and to reduce morbidity rates. In our study, the application of 5-Aminolevulinic acid (5-ALA), a precursor in the heme biosynthesis pathway, led to Protoporphyrin IX (PpIX) accumulation within the parathyroid gland (PTG). PpIX, a metabolite of 5-ALA, causes red fluorescence (635 nm) when stimulated by light of a defined wavelength. Largely invisible under conventional illumination, all PTGs were fluorescence positive and detectable after PpIX targeting and blue light excitation (380-440 nm). Point spectrometry to measure fluorescence intensities, showed a fluorescence ratio between PTG and surrounding thyroid gland tissue of 5.7:1 (p < 0.001). Fluorescence guided PTG biopsies showed no false positive findings in histology. 5-ALA induced PpIX fluorescence to detect PTGs suggests to be a highly sensitive intraoperative visualization method. Hence, the performance of minimally invasive video-assisted parathyroidectomy will be facilitated by this innovative technique.

No abstract