TRAIL is a promising therapeutic agent for human malignancies. TRAIL often requires mitochondrial dysfunction, referred to as the Type II death receptor pathway, to promote cytotoxicity. However, numerous malignant cells are TRAIL resistant due to inhibition of this mitochondrial pathway. Using cholangiocarcinoma cells as a model of TRAIL resistance, we found that Hedgehog signaling blockade se...

The hedgehog signalling pathway is a conserved mechanism which acts in inductive processes in both vertebrate and invertebrate development to direct growth and patterning. In Drosophila, the secreted Hedgehog protein acts as a signal to induce non-autonomous activation in adjacent cells of either the decapentaplegic or wingless genes (both of which encode growth factor-like molecules), via inac...

PURPOSE Research has revealed abnormal activation of the hedgehog pathway in human malignancies. The present study was undertaken to examine the expression and functional involvement of the hedgehog pathway in endometrial tissues. EXPERIMENTAL DESIGN The expression of sonic hedgehog (Shh), patched (Ptch), Smoothened (Smo), and Gli1 was examined in various endometrial tissues and endometrial c...

Communication between cells pervades the development and physiology of metazoans. In animals, this process is carried out by a relatively small number of signaling pathways, each consisting of a chain of biochemical events through which extracellular stimuli control the behavior of target cells. One such signaling system is the Hedgehog pathway, which is crucial in embryogenesis and is implicat...

Mutations in hedgehog signaling pathway genes, especially PTC1 and SMO, are pivotal to the development of basal cell carcinomas. The study of basal cell carcinoma gene expression not only may elucidate mechanisms by which hedgehog signaling abnormalities produce aberrant tumor cell behavior but also can provide data on in vivo hedgehog target gene control in humans. We have found, in comparison...

Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/- mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lowe...

We study the radial-hedgehog solution on a unit ball in three dimensions, with homeotropic boundary conditions, within the Landau-de Gennes theory for nematic liquid crystals. The radial-hedgehog solution is a candidate for a globally stable configuration in this model framework and is also a prototype configuration for studying isolated point defects in condensed matter physics. We use a combi...

The arrival of retinal axons in the brain of Drosophila triggers the assembly of glial and neuronal precursors into a 'neurocrystalline' array of lamina synaptic 'cartridges'. Hedgehog, a secreted protein, is an inductive signal delivered by retinal axons for the initial steps of lamina differentiation. In the development of many tissues, Hedgehog acts in a signal relay cascade via the inductio...

Activation of the hedgehog pathway is reported in lung cancer, but its frequency remains unknown. We examine activation of this pathway in lung cancers by in situ hybridization and immunohistochemstry, and find that less than 10% of the tumors have elevated hedgehog target gene expression. We further identify a cell line NCI-H209 and two primary tumors with no detectable Su(Fu), a negative regu...

The Nodal and Hedgehog signaling pathways influence dorsoventral patterning at all axial levels of the CNS, but it remains largely unclear how these pathways interact to mediate patterning. Here we show that, in zebrafish, Nodal signaling is required for induction of the homeobox genes nk2.1a in the ventral diencephalon and nk2.1b in the ventral telencephalon. Hedgehog signaling is also require...