The KRAS oncogene product is considered a major target in anticancer drug discovery 1, 2,
3. However, direct interference with KRAS signalling has not yet led to clinically useful drugs
3, 4, 5, 6, 7, 8. Correct localization and signalling by farnesylated KRAS is regulated by the …

Despite intense efforts in pharmaceutical industry and academia, a therapeutic grip on
oncogenic Ras proteins has remained elusive. Mutated Ras is associated with∼ 20− 30% of
all human cancers often not responsive to established therapies. In particular, K-Ras, the …

K-Ras4B is a small GTPase whose selective membrane localization and clustering into
microdomains are mediated by its polybasic farnesylated C-terminus. The importance of the
subcellular distribution for the signaling activity of K-Ras4B became apparent from recent in …

The prenyl-binding protein PDEδ is crucial for the plasma membrane localization of
prenylated Ras. Recently, we have reported that the small-molecule Deltarasin binds to the
prenyl-binding pocket of PDEδ, and impairs Ras enrichment at the plasma membrane …

K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras
signaling activity requires correct cellular localization of the GTPase. The spatial
organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras …

DNA-encoded chemical libraries have emerged as a powerful tool for hit identification in the
pharmaceutical industry and in academia. Similar to biological display techniques (such as
phage display technology), DNA-encoded chemical libraries contain a link between the …

Objective: To develop evidence based recommendations for the management of hip
osteoarthritis (OA). Methods: The multidisciplinary guideline development group comprised
18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist, representing 14 …

BACKGROUND Osteoarthritis (OA) is the most common joint disease encountered
throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in
1998 to determine the methodological and logistical approach required for the development …

Background and Purpose—We hypothesize that in acute middle cerebral artery stroke,
thrombus lengths measured in thin-slice nonenhanced CT images define a limit beyond
which systemic thrombolysis will fail to recanalize occluded arteries. Methods—In 138 …

The purpose of our study was to investigate the efficacy of an acute lymphoblastic leukemia
(ALL)-type treatment with moderate-dose, prophylactic cranial irradiation and without local
radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). From April 1990 to …