Wednesday, February 5, 2014

Specific cytokines involved in endo

"The researchers found a distinctive profile of cytokine activity associated with certain symptoms, specifically ovarian and rectovaginal lesions. This pattern, which included 13 cytokines, was also negatively correlated with patient fertility. Many of the inflammatory compounds that make up the newly discovered signature have previously been implicated in endometriosis. One of the key regulators of this signature that the researchers identified is c-Jun, a protein that drives inflammation. This molecule has been linked to endometriosis before, and a drug that inhibits c-Jun is now in clinical trials to treat the disease. The researchers also found that many of the molecules that make up their signature are secreted by macrophages, a type of immune cell that acts as a sentinel — patrolling tissues, digesting foreign material, and presenting it to other immune cells.
The team is now investigating the triggers for this immune response, which are likely not the same in every patient. They plan to analyze tissue from subsets of endometriosis patients, including those who experience infertility and those with deeply infiltrating lesions affecting the colon and other pelvic organs....Such studies could help lead to new drug targets, as well as a better understanding of a highly complex disease, the researchers say."

"The research, published in the journal Science Translational Medicine, is influenced by Griffith’s own experience as a breast cancer survivor. When she was diagnosed with breast cancer in 2010, Griffith’s experience with that disease was very different than with her lifelong struggle with endometriosis. Doctors quickly did molecular tests to discern the underlying molecular drivers of her cancer and to help select the treatment most likely to work. She wanted to find a way to bring that personalized medicine approach to endometriosis, which is usually treated with a combination of hormones and surgery.
“We’re trying to start a conversation with the community where we can say, like cancer, the surgical appearance is part of what you use to understand the patient situation. But there are molecular markers that are very informative about mechanism,” Griffith said.
In the study, Griffith and colleagues studied samples taken from 77 women with suspected endometriosis. The samples, removed during surgery, were analyzed for immune system molecules involved in inflammation. The researchers were searching for patterns that would give them new ways to subdivide the women, who had variable levels of infertility and pain and may even have different causes driving their disease. Instead of looking for just one immune system protein that was elevated, they looked for networks of molecules that seemed to be elevated in concert; that approach is key because the disease is complex and not likely to be due to a single errant protein.
"In about a third of the women with confirmed endometriosis, they found a network of 13 immune system proteins that were elevated. They cross-referenced those to try and figure out what kind of immune cell might be releasing them, which led them back to a particular type of cell called a macrophage. Using that information, they selected a specific experimental drug that they thought would inhibit the process and administered it to the patient cells in a dish. They found that they could reduce the inflammatory factors secreted by that cell.
"The work is early and Griffith said her hope would be that a pharmaceutical company might pick up on the research and move toward developing a targeted drug that could be tested in a subset of patients likely to respond. They also hope to look in a larger patient population, to see if they can find similar hallmarks that could point to new ways to diagnose and treat the disease."