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.
Gastrointestinal stromal tumors (GISTs) arising from mesenchymal cells are characterized by the expression of c-kit and by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) ...have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. 101 patients (54f/47m) with a mean age of 64.1a 17a; 94a years were surgically treated for a GIST within a 10-year period of time. 28/101 (28%) of the patients were affected by metastases (mean follow-up 4.5a). In 36/101 cases (36%) GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97/101 GIST (96%). In patients with high-risk GIST the expression of p16 expression was highly predictive for poor prognosis i.e. the development of recurrence or metastases (p=0.006) and poor survival (p=0.004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (p=0.041). The disease specific and disease free one-, three- and five-year survival rate was 96%, 90% and 85% as well as 81%, 77% and 72% respectively. Primary tumour state, tumour size and high-risk classification were confirmed as relevant predictors for unfavourable prognosis in GIST (p<0.001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for Aa "very high-risk GISTAa".
We present updated preliminary results for the nucleon electromagnetic form factors for non-perturbatively \(\mathcal{O}(a)\) improved Wilson fermions in \(N_f=2\) QCD measured on the CLS ensembles. ...The use of the summed operator insertion method allows us to suppress the influence of excited states in our measurements. A study of the effect that excited state contaminations have on the \(Q^2\) dependence of the extracted nucleon form factors may then be made through comparisons of the summation method to standard plateau fits, as well as to excited state fits.
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