Postnatal Development of Hepatic Innate Immune Response

The liver is an immunocompetent organ that plays a key role in the immune response to infections, and the development of hepatic immune function during early postnatal stages has not been thoroughly characterized. This study analyzed the constitutive expression of complement factors, namely C3 and C9, and pattern recognition receptors, namely CD14, toll-like receptor (TLR)-4, and lipopolysaccharide binding protein (LBP), in the liver of postnatal day (P)1, P21, and P70 rats, and compared the kinetics of induction of cytokines and chemokines in the liver of P 1 and P 21 animals. Our studies found that while the mRNA expression of C3, C9, CD14, and TLR-4 was lower in P1 animals, the mRNA level of LBP was higher in P1 animals as compared to older animals, and that the kinetics of induction of cytokines and chemokines was significantly delayed in P1 as compared to P21 liver following LPS stimulation. Our data suggest that hepatic innate immunity is deficient in the neonates and undergo significant development during early postnatal life

Targeting tyrosine kinases for treatment of ocular tumors

Uveal melanoma is the most common intraocular primary malignant tumor in adults, and retinoblastoma is the one in children. Current mainstay treatment options include chemotherapy using conventional drugs and enucleation, the total removal of the eyeball. Targeted therapies based on profound understanding of molecular mechanisms of ocular tumors may increase the possibility of preserving the eyeball and the vision. Tyrosine kinases, which modulate signaling pathways regarding various cellular functions including proliferation, differentiation, and attachment, are one of the attractive targets for targeted therapies against uveal melanoma and retinoblastoma. In this review, the roles of both types of tyrosine kinases, receptor tyrosine kinases and non-receptor tyrosine kinases, were summarized in relation with ocular tumors. Although the conventional treatment options for uveal melanoma and retinoblastoma are radiotherapy and chemotherapy, respectively, specific tyrosine kinase inhibitors will enhance our armamentarium against them by controlling cancer-associated signaling pathways related to tyrosine kinases. This review can be a stepping stone for widening treatment options and realizing targeted therapies against uveal melanoma and retinoblastoma.N