Activin receptor-like kinases (ALKs), members of the type I activin receptor family, belong to the serine/threonine kinase receptors of the transforming growth factor-β (TGF-β) superfamily. ALKs mediate the roles of activin/TGF-β in a wide variety of physiological and pathological processes, ranging from cell differentiation and proliferation to apoptosis. For example, the activities of ALKs are associated with an advanced tumor stage in prostate cancer and the chondrogenic differentiation of mesenchymal stem cells. Therefore, potent and selective small molecule inhibitors of ALKs would not only aid in investigating the function of activin/TGF-β, but also in developing treatments for these diseases via the disruption of activin/TGF-β. In recent studies, several ALK inhibitors, including LY-2157299, SB-431542 and A-83-01, have been identified and have been confirmed to affect stem cell differentiation and tumor progression in animal models. This review discusses the therapeutic perspective of small molecule inhibitors of ALKs as drug targets in tumor and stem cells.

No abstract

Infection with Aspergillus fumigatus can cause life-threatening diseases in immunocompromised patients with an unacceptable mortality rate. Angioinvasion is one of the features of severe invasive aspergillosis. Neutrophils are short-lived immune cells regulated by colony-stimulating factor 3 (CSF3) that play a key role in anti-fungal immune responses. To investigate the interactions between A. fumigatus and the host immune cells, such as neutrophils, we stimulated human umbilical vein endothelial cells (HUVECs) with the conidia of A. fumigatus, and co-cultured them with human neutrophils. Apoptosis and functions of neutrophils were analyzed. Our results showed that HUVECs upregulate the expression of CSF3, which could reduce the apoptosis of neutrophils while enhancing their functions. Lack of CSF3 was associated with enhanced apoptosis of neutrophils with impaired function. This work indicated that the CSF3 is required for neutrophil survival and function, at least in the early stages of A. fumigatus infection.