07 November 2012

To assess the aggressiveness of diseases, an analysis of the activity of cathepsins will help

Researchers at the Georgia Institute of Technology, working under the guidance of Associate Professor Manu Platt, have developed a technique that allows using a blood sample to predict the activity of the production of cathepsin enzymes in the patient's body that destroy extracellular matrix proteins. These enzymes are related to the mechanisms of development of diseases such as atherosclerosis, osteoporosis and cancer, so the new method will not only assess the aggressiveness of the disease, but also predict the patient's reaction to certain drugs.

The authors obtained blood samples from 14 healthy volunteers and isolated monocytes from them, after which, with the help of special biological factors, they stimulated their differentiation into macrophages or osteoclasts. In this way, they reproduced what was happening in the body: monocytes receive signals from damaged tissues, leave the bloodstream and turn into macrophages or osteoclasts involved in tissue changes occurring in atherosclerosis, cancer and osteoporosis.

During the differentiation of monocytes, the researchers assessed the levels of transient activity of kinase family enzymes in these cells, and then compared the values obtained with the levels of activity of the production of four types of cathepsins: K, L, S and V. According to Platt, the amount of cathepsins produced varied greatly in cell cultures isolated from blood samples from different donors.

After that, using the approaches of systems biology, the authors developed a mathematical model that allows predicting the level of cathepsin activity and identifying patients who are characterized by the highest values of this indicator.

Despite the wide range of cathepsin activity in the analyzed samples, the prediction accuracy when using the new model was 90-95%.

The next stage of the work will be to evaluate the possibility of using the model to predict the activity of cathepsins based on the results of blood analysis of patients with atherosclerosis, osteoporosis and cancer. The ultimate goal of the researchers is to develop a method that will allow doctors to determine the degree of aggressiveness of the patient's disease at the time of diagnosis. This will allow you to immediately select the optimal personalized therapy protocols.

Article by Keon-Young Park et al. Patient specific proteolytic activity of monocyte-derived macrophages and osteoclasts predicted with temporary kinase activation states during differentiation is published in the journal Integrative Biology.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Georgia Institute of Technology:
Blood Testing Predicts Level of Enzymes that Facilitate Disease Progression.

07.11.2012

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