Cover Picture: Proteomics – Clinical Applications 4/10

Abstract The tale of two oxen: Deet and Red A lot of drivers thought that they owned Deet and Red (or DetOx and RedOx). In fact, the two oxen were a corporation run by shareholders, one of the larger was GNMT, also known as Jimmy T, short for glycine N ‐methyltransferase. Trained by Mother Nature, they were selected for their abilities to clean up chemical wastes using SAM and associated liver helpers. Liao et al. got interested in how these “dumb” oxen could do such meticulous work; hence, they pulled out their favorite proteomic tools and set to work. They constructed a knockout mouse line with 4.5 of 6 GNMT exons deleted and looked at changes in regulation and expression compared with WT. Loss of Jimmy T led to increased chances of cancer development. It appears to be due to overexpression of several detoxification and anti‐oxidation enzymes. There are more questions that must be answered before we understand oxen. Liao, Y.‐J. et al ., Proteomics Clin. Appl . 2010, 4 , 394–406. Children in darkness: Initial work on proteomics of retinoblastoma Retinoblastoma (Rb) is not an uncommon cancer – 5–7 cases per 100 000 live births – and it can be treated relatively effectively, if the child is in the right country (survival 90–98% in Europe and North America; <25% in parts of Africa). The major difference is the stage of the tumor when first seen by an ophthalmologist. Mallikarjuna et al. report here on initial studies comparing Rb and healthy adult retinas using a wide range of proteomic tools: 2‐DE/MALDI‐TOF/TOF, RT‐PCR, immunohistochemistry, immunoanalysis, etc . They examined 29 Rb tumors and 14 healthy controls by 2‐DE and turned up 27 differentially expressed proteins out of ∼450 protein spots common to cases and controls: 16 Rb proteins were upregulated, and 11 downregulated. In terms of functions, most of the major organelles were affected by one or more up‐ or down‐shifted function. There are hints of hope, but much remains dark. Mallikarjuna, K. et al ., Proteomics Clin. Appl. 2010, 4 , 449–463. A standard that will stand? You're in for it! It was a dark and rainy November night in Versailles when the discussion began. The lights on the palace left the puddles on the slate walks in the shadows. One thing was clear – there was a rocky road ahead. It took only two different group reports that night at HUPO 1 in 2002 to spotlight the major and considerable issues ahead for those who had elected to develop urine as a source of biomarkers for diagnostic and therapeutic applications. Only slightly less risky has been the path of those developing urine as a biological standard material. Now Mischak et al. ( et al. including over 30 authors from more than a dozen institutions) report some of the successes and failures in developing urine as a bio‐standard. After 8 years, we are closer, “but”, as the man says: “no cigar”. Mischak, H. et al ., Proteomics Clin. Appl . 2010, 4 , 464–478.