Stories of Success
from the Institute for Science and Health

The Institute for Science and Health does more than support groundbreaking research. Our benefactors are helping to support some of the most exciting breakthroughs in health-science worldwide. To share our latest success stories from around the globe, click on the titles below.

• Study in Mice Links Smoking During Pregnancy to Asthma in the Offspring; A Gender Connection
• "Signal-Smart" Virus Being Developed to Target Pancreatic Cancer
• Diagnosis of Early Pancreatic Cancer Using Novel Immuno-markers

Study in Mice Links Smoking During Pregnancy to Asthma in the Offspring; A Gender Connection

Is smoking during pregnancy related to development of asthma or breathing problems in children? Well-documented scientific data indicate that moms who smoke during pregnancy increase the risk of a variety of adverse health outcomes in their children. However, little data exist on the health effects of particular components of cigarette smoke or how these might cause or worsen respiratory (airway) problems. A new animal study underway on prenatal exposure to cigarette smoke by the Institute for Science and Health is yielding intriguing results suggesting that exposure to cigarette smoke during gestation produces enhanced airway responsiveness that could be related to chronic airway diseases such as asthma. The data further suggest that such adverse effects may be more pronounced in females.

Using Institute grants, the research is being performed by Dr. Judith Zelikoff at the New York University School of Medicine in the Nelson Institute of Environmental Medicine.

"Our main goal is to look at airway responsiveness in offspring exposed prenatally to cigarette smoke at maternal levels equivalent to smoking less than 1 pack of cigarettes per day," said Dr. Zelikoff. "This study could help us understand the mechanisms by which prenatal exposure to cigarette smoke might act to increase the risk of developing asthma in offspring later in life."

According to Dr. Zelikoff, "Our research focus is to both examine the effects of inhaled cigarette smoke on airway reactivity and investigate additional biological parameters important in mediating changes in such outcomes." The pulmonary and immunological effects of cigarette smoke on prenatally exposed offspring will be compared to those observed in age- and sex-matched offspring born of non-smoking mothers (pregnant mice exposed to clean, filtered air only). In addition, to determine whether prenatal exposure to cigarette smoke can worsen airway hyper-responsiveness in an already asthmatic individual, studies were also undertaken with offspring that were already "allergic".

When compared to sex-matched offspring from control, non-smoke exposed animals, female pups born from smoke-exposed mice have an exaggerated airway response to non-specific chemical stimuli that act to constrict airways, a response which is a hallmark of asthma.

The research plan involves exposing pregnant mice to cigarette smoke in both a whole, unfractionated state, and then in a gas-only (vapor) phase. The experimentation involving whole cigarette smoke and non-sensitized and "allergic" animals is nearly complete. Following the whole-smoke exposure studies, gas-phase only investigations will commence.

Dr. Zelikoff notes that it will be useful to have more data on which specific components of cigarette smoke cause the most harm. Reducing exposure to harmful agents or disease-causing compounds benefits everyone. But even more important, "Chronic airway diseases like asthma can have a serious economic and emotional impact over one's lifetime," she said. "For moms who want their children to be born healthy and to have a healthy future, cigarette smoking is an easily modifiable risk factor."

"Signal-Smart" Virus Being Developed to Target Pancreatic Cancer

Every year, approximately 32,000 individuals die from pancreatic cancer. Of those newly diagnosed with pancreatic cancer, few survive beyond five years-and many die much sooner. Still, pancreatic cancer remains a mysterious and under-researched disease.

A new study sponsored by the Institute for Science and Health offers hope that viruses traditionally known to cause illness and discomfort in humans can now also be used to fight deadly cancers. The research effort, funded by a seed grant from the Institute and additional funds from the Department of Defense, is being led by Dr. Faris Farassati at the University of Minnesota School of Medicine in Minneapolis . Dr. Farassati is an assistant professor in the Division of Hematology, Oncology, and Transplantation in the Department of Medicine.

The research focuses upon targeting cells that display an over-activity of a cancer-promoting biochemical pathway triggered by an oncogene called Ras . While the Ras signaling pathway is involved in 35-40 percent of all human cancers, remarkably, mutations in Ras are found in over 90 percent of pancreatic cancers. "Based on a previous body of research, we began to suspect that, by targeting specific cells with elevated Ras activity, we could fight pancreatic cancer," said Dr. Farassati.

Previous studies by Farassati, published in the prestigious journal, Nature Cell Biology , and also selected for international press coverage, have revealed that natural Herpes Simplex Virus (HSV) shows a significant preference toward infecting cells with high-Ras activity. In fact, some genetically engineered, "mutant" forms of HSV have been shown to attack certain brain tumors effectively and have passed phase I clinical trails. "Using this knowledge, we set out to engineer a modified version of herpes virus that could be used as a highly specific tool for the treatment of pancreatic cancer", said Farassati.

"The idea is to develop a mutated version of HSV capable of infecting and replicating in cells with elevated Ras activity, while ignoring cells with low Ras activity such as most normal cells. We call this type of virus 'Signal-Smart,'" he said. Such signal-smart viruses will be switched-on in pancreatic cancer cells leading to the cells' ultimate destruction.

Generating this "Signal-Smart" virus is the first step toward developing a generation of signal-specific viruses for cancer therapy that could be applied to a wide range of human malignancies. "Lung, colon, colorectal and thyroid cancers also contain mutated Ras and exhibit abnormally elevated levels of Ras activity," he noted. "Even breast and prostate cancer have molecules related to Ras that are overactive." This research also holds promise for identifying new ways to block Herpes-type infections and providing remedies for certain infectious diseases.

"We are working 110 percent overtime on this," said Dr. Farassati. "We're very grateful to the Institute for support. They are sponsoring this research at an important, fragile stage, and we intend to have something wonderful to show for it."

Diagnosis of Early Pancreatic Cancer Using Novel Immuno-markers

Pancreatic cancer is a major public health problem with about 30,000 cases every year diagnosed, resulting in about 28,000 deaths per year. The outcomes in patients with pancreatic cancer have not improved in a meaningful way over the last several decades, and the prognosis of patients with pancreatic cancer remains grim.

One of the major factors contributing to the grim prognosis is difficulty in diagnosing pancreatic cancer early when it might still be amenable to potentially curative treatment. In fact, only 25 % of the patients with pancreatic cancer are diagnosed early enough to be able to have adequate surgical resection of the tumors.

The advent of endoscopic ultrasound (EUS) with its ability to both examine the pancreas up close and strategically biopsy the pancreas using sensitive ultrasound guidance represents a major recent advance in the diagnosis of pancreatic cancer. EUS makes it possible to detect very small tumors, a majority of which can be treated and even cured. In addition, EUS-guided fine needle biopsies of these small tumors can provide a firm diagnosis with a very high degree of certainty in these patients.

However, the success of EUS is limited by difficulty in identifying cancer cells in specimens obtained from pancreatic tumors. This is because pancreatic cancer cells often look very similar to normal cells. Efforts to distinguish pancreatic cancer cells from non-cancerous cells using clinical markers have met with limited success, said Dr. Banke Agarwal, an investigator at St. Louis University School of Medicine whose research is funded by the Institute for Science and Health.

However, recent developments have prompted Dr. Agarwal's group to try some novel immunological markers. They selected a panel of five such markers. "We were fortunate to find that two of five markers seem extremely helpful in diagnosing pancreatic cancer in our studies," said Agarwal. "In a systematic evaluation of these markers for diagnosis of pancreatic cancer, we found that combined evaluation of cytologic characteristics along with staining of these immuno-markers makes it possible to diagnose pancreatic cancer in EUS-FN aspirates with 90% accuracy in cases where a definitive diagnosis of cancer was impossible based on cytology alone." In addition, pancreatic cancer could be reliably excluded when both these markers were negative. "These extremely promising immuno-markers are currently being validated for efficacy and specificity by our group in a prospective trial for pancreatic cancer diagnosis. If they live up to their promise, these immuno-markers can significantly improve our ability to diagnose early pancreatic cancer and thereby potentially improve patient outcomes."