02 March 2010

From the cutting edge of science: a digest of the journal Science

The most interesting, in our opinion, are the achievements in the field of biology and medicine published in the latest issues of Science and Science Translational Medicine.

It is known that many autoimmune diseases, which include rheumatoid arthritis, affecting small joints, systemic lupus erythematosus, characterized by damage to small vessels and manifested by rash–induced redness in the shape of a butterfly on the bridge of the nose and cheeks, psoriasis - chronic dermatosis, atherosclerosis – a disease of the arteries, characterized by the formation of lipid plaques in them, provoking deformation and narrowing vascular lumen, type I diabetes and some other inflammatory diseases, such as Crohn's disease – chronic intestinal inflammation, as well as some oncological diseases, are associated with mutant forms of protein A20. Protein A20 is vital for regulating the activity of another protein – nuclear transcription factor (nuclear factor kappa-B, NF-kB), because mice lacking A20 protein died at an early age from general atrophy. Impaired functioning of the NF-kB protein is also associated with chronic inflammatory, autoimmune and some oncological diseases.

Until now, it remained unknown how the A20 protein functions and how its disruption is associated with the development of inflammatory diseases. In the article Inhibition of NF-kB Signaling by A20 Through Disruption of Ubiquitin Enzyme Complexes, published on February 26 in the journal Science, specialists from the University of Miami and from the University of California at San Francisco, working under the leadership of Edward Harhaj, revealed the molecular relationship between proteins A20, NF-kB and the development of inflammation. They found that protein A20, participating in the ubiquitin signaling pathway - the mechanism of cellular degradation of proteins, suppresses the occurrence of inflammation by inhibiting the NF-kB protein.

In the latest issue of the journal Science Translational Medicine, two articles deserve special attention, one of which is devoted to a highly sensitive personalized technique for detecting cancer cells remaining in people's blood after a course of anti-cancer therapy, and the second is a commentary on the first. In the article Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing, scientists from Johns Hopkins University in Baltimore and their colleagues from the biotechnology company Life Technologies Corporation, working under the leadership of Victor Velculescu, describe a method for developing individual DNA biomarkers characteristic of a particular patient's cancer, which allow with an accuracy of 0.001% to detect cancer cells remaining in the tissues surrounding the tumor or in the patient's blood after surgery, chemotherapy or radiotherapy. Compared to the available cancer biomarkers (based, for the most part, on the detection of tumor–specific proteins, such as PSA - prostate-specific antigen), the technique developed by the Velculescu group and called PARE (personalized analysis of rearranged ends - personalized analysis of reorganized DNA ends) has several advantages: high specificity, sensitivity and relatively a small cost (about $5000), which tends to decrease in the near future. The high sensitivity of PARE will allow doctors to react more quickly in case of detection of cancer cells remaining after the treatment. Such a strategy gives chances for a complete cure of the patient from cancer. In an accompanying article by the editor of Cancer Sequencing Gets a Little More Personal, Ludmila Prokunina-Olsson and Stephen Chanock from the US National Cancer Institute (NCI) note that the introduction of the PARE technique into clinical practice should be preceded by additional studies aimed at assessing the accuracy of detecting DNA reorganization in cancer genomes, to determine the areas of the genome most susceptible to such mutations, as well as to reduce the cost of the diagnostic procedure.

Daria Chervyakova
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Science02.03.2010

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