BACKGROUND Recent studies have indicated hedgehog pathway plays a role in carcinogenesis of certain cancers. We investigated the clinical significance of its signaling components, including Sonic hedgehog (Shh), Patched (Ptch), and Gli-1, in oral squamous cell carcinoma (OSCC). METHODS By immunohistochemistry, we determined Shh, Ptch, and Gli-1 expression in surgical specimens from 40 patient...

The spread of chemicals, including insecticides, into the environment often raises public health concerns, as exemplified by a recent epidemiologic study associating in utero piperonyl butoxide (PBO) exposure with delayed mental development. The insecticide synergist PBO is listed among the top 10 chemicals detected in indoor dust; a systematic assessment of risks from PBO exposure, as for many...

Sonic hedgehog (Shh) is a putative morphogen secreted by the floor plate and notochord, which specifies the fate of multiple cell types in the ventral aspect of the vertebrate nervous system. Since in Drosophila the actions of Hh have been shown to be transduced by Cubitus interruptus (Ci), a zinc finger transcription factor, we examined whether a vertebrate homolog of this protein can mediate ...

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh) signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent ther...

The cut-off for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) defining airflow limitation for chronic obstructive pulmonary disease (COPD) is still contested. We assessed airflow limitation prevalence by the lower limit of normal (LLN) of Global Lungs Initiative (GLI) 2012 reference values and its predictive ability for all-cause mortality and hospitalisation in very old ad...

Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pat...

The three vertebrate Gli proteins play a central role in mediating Hedgehog (Hh)-dependent cell fate specification in the developing spinal cord; however, their individual contributions to this process have not been fully characterized. In this paper, we have addressed this issue by examining patterning in the spinal cord of Gli2;Gli3 double mutant embryos, and in chick embryos transfected with...

Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP-dependent potassium (K-ATP) channels, blocks the cardioprotective effects of mitochondrial K-ATP channel openers and induces apoptosis in rodent pancreatic islet β-cell lines. However, littl...

Protein kinase A (PKA) is an evolutionarily conserved negative regulator of the hedgehog (Hh) signal transduction pathway. PKA is known to be required for the proteolytic processing event that generates the repressor forms of the Ci and Gli transcription factors that keep target genes off in the absence of Hh. Here, we show that complete loss of PKA activity in the mouse leads to midgestation l...