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Archive - Aug 31, 2011

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Modified Toxin from Sea Bacteria Shows Potential As Anti-Colon-Cancer Drug

University of Florida (UF) researchers have modified a toxic chemical produced by tiny marine microbes and successfully deployed it against laboratory models of colon cancer. In an article published online on August 31, 2011 in ACS Medicinal Chemistry Letters, UF medicinal chemists describe how they took a generally lethal byproduct of marine cyanobacteria and made it more specifically toxic — to cancer cells. When the scientists gave low doses of the modified compound to mice with a form of colon cancer, they found that it inhibited tumor growth without the overall poisonous effect of the natural product. Even at relatively high doses, the agent was effective and safe. "Sometimes nature needs a helping human hand to further optimize these products of evolution to treat human diseases," said the article’s senior author, Dr. Hendrik Luesch, an associate professor of medicinal chemistry at UF's College of Pharmacy. "Based on what we learned about apratoxins' mechanism of action, we knew this compound class had great potential for use in anticancer therapies; however, the natural product itself is too toxic to become a therapeutic." The researchers synthesized several apratoxin compounds that were similar to the original, except for slight differences in composition, designing one that proved to be extremely potent against the cancer cells in cultures and in mice, but without the overwhelming toxicity. The compound acts as a single agent to reduce levels of two types of proteins that are targeted by cancer research labs around the world — growth factors, and enzymes called tyrosine kinases, which act as receptors for the growth factors. Known as apratoxin S4, the compound strips colon cancer cells of their ability to both secrete and use naturally occurring factors that fuel growth — something that Dr. Luesch, postdoctoral chemist Dr.

Genetic Condition May Underlie Many Cases of Personal Bad Odor

Scientists from the Monell Center in Philadelphia report that approximately one third of patients with unexplained body malodor production test positive for the metabolic disorder trimethylaminuria (TMAU). A definitive diagnosis offers relief to these individuals, as symptoms of TMAU can hinder social and workplace interactions and cause psychological distress. But once the disease is identified, these debilitating symptoms can be ameliorated using changes in diet and other approaches. "Health care professionals must arrive at a correct diagnosis to suggest appropriate treatment," said study lead author Dr. Paul M. Wise, a sensory psychologist at Monell. "This research raises awareness of both the disease and also the proper methods of diagnosis and treatment." TMAU is a genetically-transmitted disease that inhibits the ability of an enzyme to metabolize or transform trimethylamine (TMA), a chemical compound produced naturally from many foods. TMA has a foul, fishy odor. At lower concentrations, it may be perceived as unpleasant or "garbage-like." Production of TMA is associated with foods rich in the dietary constituent, choline. Such foods include eggs, certain legumes, wheat germ, saltwater fish, and organ meats. The distressing symptoms of TMAU stem from the accumulation of excess TMA – and its associated unpleasant odor – which is then excreted from the body in urine, sweat, saliva, and breath. Importantly, TMA production and associated odor symptoms depend on what foods have been recently eaten and therefore may occur in irregular and seemingly unpredictable intervals. This makes the disease difficult to diagnose, as patients can appear to be odor-free when they consult a health professional.