Investigators at the University of British Columbia, have found a way to turn on the brakes of a cell, and thus halt abnormal blood-cell growth in a range of 1) ___ and autoimmune disorders, and blood cancers. The immune system relies on white blood cells called, 2) ___, to defend the body against infectious pathogens such as bacteria and viruses. In a healthy body, leukocytes are strictly controlled and turned off when no longer needed. This off-switch is controlled by a 3) ___ called “SHIP” – standing for SH2-containing inositol 5’phosphatase. SHIP, which is only present in 4) ___ cells, was discovered in 1997 by, a senior scientist at the BC Cancer Research Center. It regulates the PI3 kinase (PI3K) pathway which is essential for cell growth, survival and 5) ___ cell activation. Inappropriate or persistent activation of the PI3K pathway, can result in serious inflammatory/immune diseases or blood cancers such as multiple 6) ___, leukemia and lymphoma. Aiming to find new drugs for treatment of blood borne diseases, a team searched for drugs that could modulate SHIP. The team screened a library of sea sponge extracts for molecule compounds that can turn SHIP on. Sea sponges are a rich source of novel bio-active 7) ___, created by nature, to protect themselves against marine predators. Interestingly, many of these compounds possess important medicinal properties. The sponge library has already produced other agents with interesting biological properties on 8) ___ cells, some of which are in clinical development as potential drugs for treatment of human diseases. The researchers identified a compound, now known as AQX-MN100. It is able to inhibit immune and blood cell activation both in the test tube and in mouse models of human inflammatory disease and lymphoma by activating SHIP. This is an entirely new paradigm for controlling run-away cells. Previous research efforts were aimed at trying to control the cells through blocking stimulation 9) ___. In a run-away train analogy, this would be like taking your foot off the accelerator and the train will eventually stop when it runs out of fuel vs. this new approach of directly applying the brakes. Since SHIP is only found in 10) ___/___ cells, side-effects of SHIP-based therapy on other cells of the body, are expected to be limited. The AQX-MN100 discovery has been validated by proof-of-principal grants from the Canadian Institutes of Health Research (CIHR) aimed at translating basic research findings into clinically applicable therapy. This research is highlighted in the Sept. 15 edition of Blood, Journal of the American Society of Hematology.

ANSWERS: 1) inflammatory; 2) leukocytes; 3) protein; 4) blood; 5) immune; 6) myeloma; 7) compounds; 8) mammalian; 9) signals; 10) immune/blood

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