Screening approaches for lung cancer by blood-based biomarkers: Challenges and opportunities.

Lung cancer (LC) is one of the leading causes for cancer-related deaths in the world, accounting for 28% of all cancer deaths in Europe. Screening for lung cancer can enable earlier detection of LC and reduce lung cancer mortality as was demonstrated in several large image-based screening studies such as the NELSON and the NLST. Based on these studies, screening is recommended in the US and in the UK a targeted lung health check program was initiated.

EphB4 provides survival advantage to squamous cell carcinoma of the head and neck.

The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play critical roles in blood vessel maturation, and are frequently overexpressed in a wide variety of cancers. We studied the aberrant expression and biological role of EphB4 in head and neck squamous cell carcinoma (HNSCC). We tested the effect of EphB4-specific siRNA and antisense oligonucleotides (AS-ODN) on cell growth, migration and invasion, and the effect of EphB4 AS-ODN on tumor growth in vivo.

Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer.

Purpose: Vascular endothelial growth factor has a critical role in maintaining tumor microvasculature and, as such, is an attractive target for anti-angiogenic therapy. Aberrant expression of VEGF receptors, especially VEGFR2, on epithelial tumor cells allows VEGF to stimulate growth and migration of tumor cells in an autocrine and/or paracrine manner. Therefore, we studied the expression of VEGF and VEGFR2 in bladder cancer, and the relationship to disease characteristics.

EphB4 expression and biological significance in prostate cancer.

Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets.

Sphingosine kinase protects lipopolysaccharide-activated macrophages from apoptosis.

Lipopolysaccharide (LPS) signaling is critical for the innate immune response to gram-negative bacteria. Here, evidence is presented for LPS stimulation of sphingosine kinase (SPK) in the RAW 264.7 murine macrophage cell line and rat primary hepatic macrophages (HMs).

Inhibition of tumor cell growth by Triton X-100 through specific effects on cell-cycle-regulatory components.

A cross-linked form of the detergent Triton X-100, called Triton WR-1339, has been shown to reduce the spread of tumor cells in laboratory animals. However, some of these effects were controversial, probably due to the use of different tumor cell lines and varying sites of injection. In order to better understand these processes, we have used Triton X-100 and performed a molecular analysis of its growth-inhibitory function.

Generation of a monoclonal antibody to a cryptic site common to both integrin beta1 as well as gelatinase MMP9.

Integrins are one class of cell surface receptors that have been implicated in the regulation of a diverse set of cellular processes, including cell adhesion, migration, and invasion as well as gene expression, differentiation, and signal transduction. Cellular invasion not only requires the adhesive properties of integrins but also the proteolytic properties of matrix-degrading enzymes, such as the metalloproteinases (MMPs). Previous studies have shown that integrin alphavbeta3 is a receptor for MMP2, localizing its proteinase activity to the cell surface, ultimately leading to site-specific extracellular matrix (ECM) degradation.

VEGF receptor expression and signaling in human bladder tumors.

Overexpression of vascular endothelial growth factor receptors (VEGFRs) has been reported in a variety of tumor types. Here we find that 11 out of the 14 bladder tumor cell lines examined express one or more VEGF receptors. Analysis of the T24 bladder tumor cell line reveals a functional autocrine loop involving VEGF and the Flk-1 receptor.

Ionizing radiation modulates the exposure of the HUIV26 cryptic epitope within collagen type IV during angiogenesis.

Purpose: The majority of the research on the biologic effects of ionizing radiation has focused on the impact of radiation on cells in terms of gene expression, DNA damage, and cytotoxicity. In comparison, little information is available concerning the direct effects of radiation on the extracellular microenvironment, specifically the extracellular matrix and its main component, collagen. We have developed a series of monoclonal antibodies that bind to cryptic epitopes of collagen Type IV that are differentially exposed during matrix remodeling and are key mediators of angiogenesis.

Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases.

Vascular endothelial growth factor (VEGF) signaling is critical to the processes of angiogenesis and tumor growth. Here, evidence is presented for VEGF stimulation of sphingosine kinase (SPK) that affects not only endothelial cell signaling but also tumor cells expressing VEGF receptors. VEGF or phorbol 12-myristate 13-acetate treatment of the T24 bladder tumor cell line resulted in a time- and dose-dependent stimulation of SPK activity.