A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease.

Purpose: To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).

Patients And Methods: A randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61).

Narrow Spectrum Kinase Inhibitors Demonstrate Promise for the Treatment of Dry Eye Disease and Other Ocular Inflammatory Disorders.

Purpose: The purpose of this study is to determine the potential of narrow spectrum kinase inhibitors (NSKIs) to treat inflammatory eye disorders.

Methods: Human conjunctival epithelial (HCE) cells were retrieved from subjects via impression cytology. Real-time quantitative PCR (qPCR) was performed on HCE cells to determine gene expression of NSKI kinase targets and proinflammatory cytokines in dry eye disease (DED) patients versus healthy controls.

Effect of Narrow Spectrum Versus Selective Kinase Inhibitors on the Intestinal Proinflammatory Immune Response in Ulcerative Colitis.

Background: Kinases are key mediators of inflammation, highlighting the potential of kinase inhibitors as treatments for inflammatory disorders. Selective kinase inhibitors, however, have proved disappointing, particularly in the treatment of rheumatoid arthritis and inflammatory bowel disease. Consequently, to improve efficacy, attention has turned to multikinase inhibition.

Highly sensitive fluorescence detection system for microfluidic lab-on-a-chip.

We demonstrate a compact, low cost and practical fluorescence detection system for lab-on-a-chip applications. The system comprises a commercially available InGaN light emitting diode (501 nm) as light source, an organic or silicon photodiode detector, absorptive dye coated colour filters and linear and reflective polarisers. An injection moulded polystyrene microfluidic chip is used as the platform for fluorescence immunoassays for cardiac markers myoglobin and CK-MB.

Monoclonal antibodies directed to CD20 and HLA-DR can elicit homotypic adhesion followed by lysosome-mediated cell death in human lymphoma and leukemia cells.

mAbs are becoming increasingly utilized in the treatment of lymphoid disorders. Although Fc-FcgammaR interactions are thought to account for much of their therapeutic effect, this does not explain why certain mAb specificities are more potent than others. An additional effector mechanism underlying the action of some mAbs is the direct induction of cell death.

Induction of cytosolic calcium flux by CD20 is dependent upon B Cell antigen receptor signaling.

The anti-CD20 monoclonal antibody (mAb) rituximab is now routinely used for the treatment of non-Hodgkins lymphoma and is being examined in a wide range of other B-cell disorders, such as rheumatoid arthritis. Despite intensive study, the mechanism of action still remains uncertain. In the current study, anti-CD20 mAb-induced calcium signaling was investigated.

Expression of endothelial intercellular adhesion molecule-1 is determined by genotype: effects on efficiency of leukocyte adhesion to human endothelial cells.

Two biallelic polymorphisms, previously described in the human intercellular adhesion molecule (ICAM)-1 gene at codon 241 (glycine [G] to arginine [R] substitution) and codon 469 (glutamic acid [E] to lysine [K] substitution) have been associated with a number of diseases including myocardial infarction, transplant rejection, and diabetes. However, the functional significance of these polymorphisms has not been determined. ICAM-1 cell surface expression and ICAM-1-mediated leukocyte adhesion were investigated using Cos7 transfected with ICAM-1 polymorphic variants or human umbilical vein endothelial cells (HUVEC) of different ICAM-1 genotypes.

The biology of CD20 and its potential as a target for mAb therapy.

CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of almost all normal and malignant B cells. It is also the target for rituximab, the most effective anti-cancer monoclonal antibody developed to date. Rituximab has now been given to over 300,000 lymphoma patients in the last decade and interestingly is now being explored for use in other disorders, such as autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus.

CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts.

Rituximab is routinely used for the treatment of neoplasia, although the mechanism of action remains uncertain. In the current study, CD20-induced apoptosis was investigated with a panel of anti-CD20 monoclonal antibodies (mAb) in a wide range of cell lines. A hierarchy of mAb activity was apparent, with the B1 mAb generally the most potent.