PURPOSE Cumulating evidence indicates that germline variants in the Wnt, Notch, and Hedgehog pathways are involved in colon carcinoma progression and metastasis. We investigated germline polymorphisms in a comprehensive panel of Wnt, Notch, and Hedgehog pathway genes to predict time to recurrence (TTR) and overall survival in patients with stage II and III colon carcinoma. EXPERIMENTAL DESIGN...

BACKGROUND In vertebrates the "SONIC HEDGEHOG" signalling pathway has been implicated in cell-fate determination, proliferation and the patterning of many different cell types and organs. As the GLI family members (GLI1, GLI2 and GLI3) are key mediators of hedgehog morphogenetic signals, over the past couple of decades they have been extensively scrutinized by genetic, molecular and biochemical...

Aberrant activation of Hedgehog (HH) signaling has been identified as a key etiologic factor in many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling depend profoundly on interactions with other pathways, such as epidermal growth factor receptor-mediated signaling, which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancr...

Chronic inflammation in the stomach can lead to gastric cancer. We previously reported that gastrin-deficient (Gast⁻/⁻) mice develop bacterial overgrowth, inflammatory infiltrate, increased Il-1β expression, antral hyperplasia and eventually antral tumors. Since Hedgehog (Hh) signaling is active in gastric cancers but its role in precursor lesions is poorly understood, we examined the role of i...

Sonic Hedgehog (SHH) and WNT proteins are key regulators in many developmental processes, like embryonic patterning and brain development. In the brain, SHH is expressed in a gradient starting in the floor plate (FP) progressing ventrally in the midbrain, where it is thought to be involved in the development and specification of mesodiencephalic dopaminergic (mdDA) neurons. GLI2A-mediated SHH-s...

AIMS The incidence and mortality of myocardial infarction (MI) in diabetic patients are higher than in non-diabetic patients; however, the mechanisms by which diabetes results in cardiac dysfunction are poorly understood. The present study tested the hypothesis that an impaired sonic hedgehog (Shh) pathway contributes to cardiac dysfunction in type 1 diabetic mice with MI. METHODS AND RESULTS...