UNLABELLED Recent evidence implicates the insulin-like growth factor (IGF) pathway in development of Ewing sarcoma, a highly malignant bone and soft-tissue tumor that primarily affects children and young adults. Despite promising results from preclinical studies of therapies that target this pathway, early-phase clinical trials have shown that a significant fraction of patients do not benefit, ...

Insulin and insulin-like growth factor (IGF) I have 50% homology in their primary amino acid sequences. IGF-I differs structurally from insulin because it has a connecting peptide between the Aand B-chains and an octapeptide sequence at the COOH-terminal of the IGF-I molecule termed the "D" region. To determine the role of the "D" region of IGF-I in its biological activity, we have synthesized ...

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibiti...

Exercise has several hemorheological effects that we previously proposed to classify as a triphasic phenomenon: acute effects (hyperviscosity mostly due to hemoconcentration but also to some alterations of erythrocyte properties); delayed effects (hyperhydration resulting in hemodilution and hypoviscosity), and a chronic situation which can be termed hemorheologic fitness. This presentation foc...

Tremendous strides have been made in improving patients' survival from cancer with one glaring exception: brain cancer. Glioblastoma is the most common, aggressive and highly malignant type of primary brain tumor. The average overall survival remains less than 1 year. Notably, cancer patients with obesity and diabetes have worse outcomes and accelerated progression of glioblastoma. The root cau...