Kudos to young researchers: Children's Hospital Boston's fourth annual Symposium in Cellular, Molecular and Clinical Research in Surgery drew about 175 attendees. The presentations were followed by a poster session where research groups from around the hospital displayed their work. Three young investigators submitted winning posters. Here are brief summaries of their work.
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Soo-Young Kang, PhD |
Researchers have aggressively tried to curb cancer by reactivating a protein called p53, one of the body's most important natural checks against cancer cell growth. Unfortunately, the p53 gene is mutated in most human tumors, foiling this strategy. However, in the non-cancerous supportive tissue surrounding tumors, known as the stroma, p53 is much less likely to mutate. Recently, it's been discovered that the stroma interacts closely with tumors, and can help a tumor metastasize by encouraging tumor-cell migration, and then fostering growth of those cells upon arrival at the distant site.
Now, poster winner Soo-Young Kang, PhD, a fellow in the vascular biology lab of Randy Watnick, PhD, has shown that stimulating p53 activity in the stroma strikingly inhibits tumor metastasis. His team also identified a compound called prosaposin, secreted by the tumor, that inhibits metastasis by stimulating p53 in the stroma. Finally, Kang showed that p53 activation boosts production of the angiogenesis inhibitor thrombospondin-1 in the stroma, both at the primary tumor and at the metastatic site, thereby blocking development of the blood vessels tumor cells need to travel to and begin growing at distant sites. Kang believes that stimulating p53 in the stroma might be an effective way to fight cancer, even when the tumor itself has a mutated p53 gene.
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Shaun Steigman, MD, and Barbara Robinson, MD |
Everyone's heart has small amounts of heat shock proteins that protect cells against stresses such as oxygen deprivation or damage caused when blood supply returns to oxygen-starved tissue. Researchers have tried to boost amounts of the most common and protective heat shock protein, hsp70i, to help protect the heart from the rigors of cardiac catheterization or cardiopulmonary bypass surgery, but to date there's been no practical or safe way to do so. Poster winner Barbara Robinson, MD, supported by the Nina Braunwald Research Grant and working in the lab of Pedro del Nido, MD (Cardiac Surgery), led a study demonstrating that a drug called GGA, used for decades in Japan to treat gastritis and peptic ulcer disease, boosts levels of cardiac hsp70i in rabbits suffering from cardiac ischemia. A single dose was also associated with better recovery of left ventricular function, with decreases in lactate and the cardiac marker troponin, indicating less damage to the heart.
In addition to helping children recover from cardiac procedures, the research could help adults, since heat shock proteins decrease in the heart with age, says Robinson, now at Brigham and Women's Hospital. Older patients who have undergone multiple operations in the past, or are coming for further cardiac surgery—including the growing population of adults with congenital cardiac defects—might especially benefit from treatment, she says.
The lab of Dario Fauza, MD (Surgery), has come closer than any lab in the country using fetal stem cells, taken from amniotic fluid during pregnancy, to fix congenital defects in babies. These mesenchymal stem cells can form many of the tissues needed by surgeons, including muscle, skin, cartilage and even bone. The idea is to harvest them during amniocentesis—which is often done when a congenital defect is seen on ultrasound—then use them to engineer tissues to repair the defects. Now, with the help of research fellow Shaun Steigman, MD, along with staff at the Center for Human Cell Therapy, the lab recently passed an important test, showing the cells can be grown up and banked by the hundreds of millions during the four- to six-month interval between amniocentesis and birth, while meeting FDA-accredited "Good Manufacturing Practice" standards.
The team isolated cells from diagnostic amniocentesis samples from pregnant women. In six of the 11 samples, they successfully expanded, cryopreserved, thawed and re-expanded the cells in sufficient numbers to potentially use in treatment. The first application is likely to be tissue-engineered "patches" to repair congenital diaphragmatic hernias—openings in the membrane separating the lungs and chest cavity from the visceral organs. A few more hurdles lie ahead before clinical trials can be conducted, but this work has taken the lab a significant step closer to being able to correct congenital defects by creating tissues from a baby's own cells.
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