Molecular analysis of Each participating institution was requested to apply its own diagnostic testing strategy on 8 sections obtained from artificial reference specimens built to harbor Overall, cell Show more
Molecular analysis of Each participating institution was requested to apply its own diagnostic testing strategy on 8 sections obtained from artificial reference specimens built to harbor Overall, cell resuspension yielded higher amounts of DNA and RNA (SNU16 61.5 ng/µl, 38100.0 pg/µl; RT112 118.0/µl, 2140.0 pg/µl, respectively) in comparison with SNU16+ RT112 mixing cell block (0.7 ng/µl DNA and 412.0 pg/µl RNA). Moreover, FFPE samples showed a higher fragmentation index (DIN 1.2 and RIN not calculated) compared with cell line resuspension (DIN 2.2 and 9.5 for SNU16 and RT112; RIN 3.9 and 6.8 for SNU16 and RT112). All participating institutions identified NGS represents the most suitable approach in molecular profiling of Show less
The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polariz Show more
The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3 Show less
Stearoyl-CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and Show more
Stearoyl-CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element-binding protein-1 (SREBP-1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP-1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP-1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP-1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP-1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs. Show less