Gene/Protein Disease Symptom Drug Enzyme Compound
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Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from 7,12-dimethylbenz(a)anthracene-induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. Whereas several cell lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing cell lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with epithelial to mesenchymal transition and putative cancer stem cells. MEK (MAP/ERK kinase) inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof-of-concept to target this pathway as a strategy to treat head and neck cancer.
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PMID:ERK1/2 regulation of CD44 modulates oral cancer aggressiveness. 2208 49

We present a novel method for inferring tissue labels in atlas-based image segmentation using Gaussian process regression. Atlas-based segmentation results in probabilistic label maps that serve as input to our method. We introduce a contour-driven prior distribution over label maps to incorporate image features of the input scan into the label inference problem. The mean function of the Gaussian process posterior distribution yields the MAP estimate of the label map and is used in the subsequent voting. We demonstrate improved segmentation accuracy when our approach is combined with two different patch-based segmentation techniques. We focus on the segmentation of parotid glands in CT scans of patients with head and neck cancer, which is important for radiation therapy planning.
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PMID:Contour-driven regression for label inference in atlas-based segmentation. 2450 63