WAGR syndrome is an acronym for the complex of symptoms seen in people who have the condition. These include Wilms tumor, a tumor of the kidneys; aniridia, absence of the iris, in the eye; genital and urinary tract abnormalities; and mental retardation. WAGR syndrome occurs in one out of every 500,000 to 1 million persons. People with WAGR syndrome lack genes that are grouped on chromosome 11. All people with WAGR syndrome lack two specific genes, called WT1 and PAX6, but each person can also be missing other nearby genes. The genetic deletions found in WAGR syndrome occur on only one of the two copies of chromosome 11. Brain derived neurotrophic factor (BDNF) is, as its name implies, produced in the brain. Studies of mice had determined that animals missing a working copy of the BDNF gene were prone to excessive eating and obesity. According to an article published in the New England Journal of Medicine (2008;359:918-927), BDNF, which also plays a role in long term memory, appears to be involved in regulating how much people eat and their likelihood of becoming obese. The study evaluated children and adults with WAGR syndrome, where some of the people also lack a gene for BDNF. Interestingly, people in this subgroup also have unusually large appetites and a strong tendency towards obesity. WT1 and PAX6 are located in the region of the chromosome that’s near the gene for BDNF. For this reason, chromosome 11 was examined from WAGR syndrome patients to learn if the gene for BDNF was also affected. For the current study, analyses of chromosome 11 was conducted in 33 patients with WAGR syndrome. A total of 19 patients (58%) had deletions of all or a major proportion of one copy of the gene for BDNF. By age 10, all of the 19 were obese and were reported to have a strong tendency to overeat. Moreover, all of the 19 had blood levels of BDNF that were roughly 50% lower than those of patients who had two working copies of the BDNF gene. The patients who had two working copies of the BDNF gene were no more likely to develop childhood onset obesity than the general population, and did not report unusually high levels of overeating. BDNF is believed to work in combination with a variety of other substances that regulate appetite and body weight. Chief among these is leptin, a hormone found to be involved in signaling hunger. Release of BDNF in the hypothalamus, a part of the brain involved in controlling eating, is believed to be indirectly triggered by leptin. Studies of the relationship between the two, and of BDNF’s action on tissues, may lead to the development of new drugs to treat obesity in some individuals.

Molecular biologists, at St. Jude Children’s Research Hospital in Tennessee, have found that brain tumors appear to arise from cancer 1) ___ cells that live inside tiny protective ‘niches’ formed by blood vessels in the brain. Breaking down these niches is a promising strategy for eliminating the tumors and preventing them from re-growing. These researchers have found that drugs that block new 2) ___ vessel formation can destroy the protected areas and stop cancer from developing. Figuring out a way to wipe out brain tumors has been a mystery. But now, a new discovery may offer clues and hope for those with even the most hard-to-treat tumors. For years, researchers thought all 3) ___ inside a tumor were the same. But recently, they’ve discovered something different — a small group of cancer stem cells, give rise to all the cells that make up the 4) ___. Research showed those cancer stem cells (CSCs) live close to blood vessels, which 5) ___ them. In lab experiments, it has been shown that drugs that target the blood vessels also destroy the cancer stem cells and can ultimately wipe out the tumor. If those cells can be 6) ___, there can be a devastating effect on the disease. Drugs like Avastin and Tarceva are now being tested in humans to see if they can target the cancer stem cells, as a tangible way of actually getting at the heart of the disease. Other cancers, like those of the blood and colon, also contain cancer stem cells and may be treated in a similar way in the future. Scientists previously believed that tumors are lumps of cancerous 7) ___ that must be completely removed or destroyed to cure a patient. But over the last five years, cancer researchers have learned that not all cancer cells are created equal. In the same way that normal tissue in the body is generated from 8) ___ cells, so is cancer. CSCs are the ultimate 9) ___ of the tumor, consistently supplying it with new cells. Researchers have identified the CSCs for acute myeloma leukemia and four types of brain cancer. So it is possible that we need not kill all cancer cells to rid a patient of the disease. Targeting the CSCs specifically might be much more efficient. To find a weakness for CSCs, neurobiologists at St. Jude compared them to noncancerous neural stem cells. These neural tissue generators are concentrated in regions rich in blood vessels. The vessels are lined with 10) ___ cells, which secrete chemical signals that help stem cells survive. CSCs, they discovered, required similar conditions to flourish: in over 70 human brain tumors, the CSCs were frequently located close to tiny vessels called 11) ___. When the researchers injected mice with a mix of stem and endothelial cells from human brain tumors, those animals sprouted larger tumors than the mice that received stem cells alone. The new findings from St. Jude indicate that it is possible to kill the cancer by disrupting the shielded compartments in the small capillaries of the brain where CSCs reside. Anti-angiogenic drugs, such as Avastin, block the formation of new blood vessels. In tests with mice, those same drugs cause a significant 12) ___ in cancer stem cells and slow tumor growth. Human clinical trials are currently in progress at St. Jude to determine the effectiveness of Avastin and another anti-angiogenic drug in eliminating tumors and preventing their recurrence in children with brain cancers.

ANSWERS: 1) stem; 2) blood; 3) cells; 4) cancer; 5) fuel; 6) targeted; 7) tissue; 8) stem; 9) source; 10) endothelial; 11) capillaries; 12) drop