Concomitant intrauterine growth restriction alters the lipoprotein profile in preeclampsia.

OBJECTIVE: Preeclampsia and intrauterine growth restriction (IUGR) are related conditions. We aimed to characterise common lipid changes. METHODS: Triglyceride and cholesterol levels of patients 24-42 weeks of gestation with IUGR (n = 52), hypertensive IUGR (HIUGR, n = 28), and preeclampsia without IUGR (PE, n = 56) were compared to a control group (CTRL, n = 167). In addition, 60 sera (n = 10 of each pathology IUGR, HIUGR, PE (without IUGR) compared to n = 30 matched CTRL) of severe early onset cases <34 weeks of gestation were chosen and further analysed by ultracentrifugation lipid subfractionation including VLDL, IDL, LDL, and HDL composition. RESULTS: In the full cohort we found low cholesterol in IUGR (p = 0.0405), while triglyceride levels were high in PE (p < 0.0001). Lipid concentrations in HIUGR did not differ significantly from CTRL. In the 60 patients analysed by lipid subfractionation, triglyceride levels were increased in the VLDL subfraction in PE (p < 0.01), however, LDL-bound ApoB and cholesterol levels were lower in IUGR and HIUGR (p < 0.0001 for total cholesterol and p < 0.001 for ApoB in both groups), but not in PE when compared to CTRL. CONCLUSION: Low cholesterol, especially LDL cholesterol levels are a feature of IUGR while high triglyceride levels are a feature of preeclampsia. Increased VLDL-triglycerides suggest a disturbed conversion to LDL in preeclampsia. Of note, the presence of IUGR in hypertensive disorders further alters lipid profiles, which may explain heterogeneous data on lipid values for preeclampsia in the literature. Study groups have to be selected carefully to avoid misinterpretation.

CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application.

The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as in non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.