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Archive - Apr 26, 2011

Targeted Topical Treatment May Prevent Melanoma

While the incidence of melanoma continues to increase despite the use of sunscreen and skin screenings, a topical compound called ISC-4 may prevent melanoma lesion formation, according to Penn State College of Medicine researchers. "The steady increase in melanoma incidence suggests that additional preventive approaches are needed to complement these existing strategies," said Dr. Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery, and director of the Penn State Hershey Melanoma Center. Researchers targeted the protein Akt3, which plays a central role in 70 percent of melanoma by preventing cell death and has the potential to prevent early stages of melanoma. "The Akt3 signaling pathway is deregulated in the majority of melanomas, making it a promising target which, if inhibited, could correct the apoptotic -- or cell death -- defect in melanocytic lesions, thereby preventing this disease," Dr. Robertson said. Isothiocyantes were identified as inhibitors of Akt3. These are naturally occurring compounds found in cruciferous vegetables like broccoli and brussels sprouts that have anticancer properties. Unfortunately, previous research showed these compounds have low chemotherapy potency on melanoma cells because high concentrations are needed to be effective. To create a more potent version, Penn State Hershey Melanoma Center researchers previously developed isoselenocyanates (e.g., ISC-4), by replacing sulfur with selenium. Researchers have now found that repeated topical application of ISC-4 can reduce tumor cell expansion in laboratory-generated human skin by 80 to 90 percent and decrease tumor development in mice skin by about 80 percent. The research also showed that the use of the compound is safe.

Brain Protein May Be Useful Target in Colorectal Cancer

Tumor progression is usually ensured by more than one proliferative mechanism. When one of these is shut down by a specifically targeted drug, other mechanisms may emerge. While these events may lead to treatment failure, they may also become an opportunity for researchers to identify novel targets to be further explored. In a paper recently published online in the journal Oncology (Vol. 79, pages 430-439, 2011), Dr. Rafael Roesler and colleagues describe a novel potential drug target in colorectal cancer. Colorectal cancer (CRC) is the fourth most common cancer in men and the third in women worldwide. It is a frequent cancer, with more than 1 million new cases every year and a poor survival rate. Rapid increases in CRC incidence have been observed mainly in emerging economies. These increases are attributed to changes in diet, life style, and patterns of physical activity. In Western countries, only 55% of the patients are alive 5 years after diagnosis, with most patients dying from metastatic disease. Although a number of treatment options are available for CRC patients, including surgery, chemotherapy, and biologic therapies targeting two different mechanisms—angiogenesis (drug: bevacizumab) and epidermal growth factor receptors (drugs: cetuximab and panitumumab)—new treatment options are required to improve survival rates. The search for novel targets led Dr. Roesler at the Federal University of Rio Grande do Sul (UFRGS) Brazil, Dr. Gilberto Schwartsmann, and graduate student Caroline Brunetto de Farias, among others, to investigate whether a brain-derived protein known to be involved in tumor growth, metastasis, and drug resistance in a number of cancers, including some non-neurological cancers, could also be found in CRC. The team led by Dr.

RAD Technology May Simplify Genome Sequencing

Take millions of puzzle pieces containing partial words and put them back together into full words, sentences, paragraphs and chapters until the book these random parts came from is rebuilt. That daunting process in not unlike sequencing an organism's genome, says University of Oregon biologist Dr. Eric A. Johnson, a member of the UO Institute of Molecular Biology. His lab developed a patent-pending technology for discovering differences between genomes called restriction-site associated DNA markers, or RAD. They have now shown that RAD can also be used to help put a genome sequence together. The original RAD technique, unveiled in 2005, led to the UO spinoff company Floragenex, which uses the technology in plant genetics. More recently, Dr. Johnson and UO colleague Dr. William A. Cresko used it to identify genetic differences in threespine stickleback, a fish, which evolved separately after environmental conditions had isolated some of the saltwater fish into freshwater habitats. Now, after three years of research, adapting the technology along the way as sequencing tools advanced, Dr. Johnson, Dr. Cresko, and three UO colleagues provide a proof-of-principle paper published online on April 13, 2011, in PLoS One. The NIH-funded research documents that the new method, called RAD paired-end contigs, works and provides accurate sequencing results. "The RAD sequence is a placeholder that identifies one small region of a genome," Dr. Johnson said. "We showed that this technique lets us gather together appropriate nearby sequences and piece them together." In just seconds, a section is completed, he said. In a matter of hours, he added, an entire genome's sequence emerges. Using the book analogy, Dr.