Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Head and neck cancer is occurring in younger patients in certain areas of the world. The factors that contribute to this process remain poorly defined, emphasizing the need for continued investigations into head and neck carcinogenesis. One potential determinant of disease development may relate to the significance of the host's intrinsic capacity to detoxify carcinogens, ie, through the phase II enzyme family, glutathione-S-transferases. Those patients with deficient GST activity may be at greatest risk. Additionally, genetic studies have suggested that certain chromosomes may be more susceptible to tobacco-induced damage. Chromosome 3p has now been identified as frequently altered both within head and neck cancers as well as within tobacco-induced malignancies. Over the past year numerous reports have addressed potential biologic determinants of not only cancer development, but also its continued progression. These factors may include altered growth factors and their receptors, changes in cellular intermediate filaments such as increased cytokeratin 19, and the production of matrix metalloproteinases. Finally, investigations continue to provide new insight into mechanisms by which abnormal gene expression may govern response to therapy. Our growing understanding of the complexity of head and neck cancer biology reinforces the need for preventive strategies, including the role of both nutritional and behavioral interventions.
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PMID:Head and neck oncology research. 808 Aug 55

Multidimensional LC-MS/MS has been used for the analysis of biological samples labeled with isobaric mass tags for relative and absolute quantitation (iTRAQ) to identify proteins that are differentially expressed in human head-and-neck squamous cell carcinomas (HNSCCs) in relation to non-cancerous head-and-neck tissues (controls) for cancer biomarker discovery. Fifteen individual samples (cancer and non-cancerous tissues) were compared against a pooled non-cancerous control (prepared by pooling equal amounts of proteins from six non-cancerous tissues) in five sets by on-line and off-line separation. We identified 811 non-redundant proteins in HNSCCs, including structural proteins, signaling components, enzymes, receptors, transcription factors, and chaperones. A panel of proteins showing consistent differential expression in HNSCC relative to the non-cancerous controls was discovered. Some of the proteins include stratifin (14-3-3sigma); YWHAZ (14-3-3zeta); three calcium-binding proteins of the S100 family, S100-A2, S100-A7 (psoriasin), and S100-A11 (calgizarrin); prothymosin alpha (PTHA); L-lactate dehydrogenase A chain; glutathione S-transferase Pi; APC-binding protein EB1; and fascin. Peroxiredoxin2, carbonic anhydrase I, flavin reductase, histone H3, and polybromo-1D (BAF180) were underexpressed in HNSCCs. A panel of the three best performing biomarkers, YWHAZ, stratifin, and S100-A7, achieved a sensitivity of 0.92 and a specificity of 0.91 in discriminating cancerous from non-cancerous head-and-neck tissues. Verification of differential expression of YWHAZ, stratifin, and S100-A7 proteins in clinical samples of HNSCCs and paired and non-paired non-cancerous tissues by immunohistochemistry, immunoblotting, and RT-PCR confirmed their overexpression in head-and-neck cancer. Verification of YWHAZ, stratifin, and S100-A7 in an independent set of HNSCCs achieved a sensitivity of 0.92 and a specificity of 0.87 in discriminating cancerous from non-cancerous head-and-neck tissues, thereby confirming their overexpressions and utility as credible cancer biomarkers.
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PMID:Discovery and verification of head-and-neck cancer biomarkers by differential protein expression analysis using iTRAQ labeling, multidimensional liquid chromatography, and tandem mass spectrometry. 1833 95