Jefferson Investigates: COVID Risks, RNA in Cancer, and a New Use for Anti-nausea Medication
Long-non-coding RNA as a common driving force in cancer, blood analysis reveals COVID-19 risks, and a common drug finds a new application.
COVID-19 still remains a threat and with new, more transmissible variants, it is critical to understand who is at highest risk of getting infected. New research from Jefferson Health explores this question in a study published in American Journal of Infection Control.
The study was conducted between March 2020 and March 2021. “We had just begun screening all patients for COVID-19, including patients coming in for procedures, such as C-sections,” says Maria Vacca, MSN, RN, the lead researcher of the study. “Thanks to EPIC, our electronic medical record (EMR), there was a large amount of data available to us for use in our study, including what role blood type and other sociodemographic variables play in contracting the virus.”
The researchers analyzed blood samples from over 27,000 patients. They found that when compared with blood type O, patients with blood type A were more likely to test positive for COVID-19, replicating earlier findings from Europe. They were also able to support findings from research occurring later in the pandemic showing that social inequities, such as race and gender, influence the likelihood of contracting the disease. This study ended prior to COVID-19 vaccinations being available to the general public.
The novel part of the findings were related to pregnancy. Pregnant women were found to be 2.5 times less likely to get COVID compared to women of child-bearing age who were not pregnant. It is unclear why the pregnant women in this study were less likely to get COVID-19. Is it related to something physiological that occurs during pregnancy, or is simply that pregnant women are more cautious in their habits, especially during a pandemic, and take fewer risks that could increase exposure to the virus?
“It’s an exciting finding and definitely warrants further study,” says Vacca.
- By Karuna Meda
The spotlight of cancer research has traditionally focused on the communications between DNA and the proteins it encodes. When DNA damage causes genetic mutations, proteins made from those genes that normally send crucial messages or control cell function are not made. In some cases, this leads to the cell multiplying uncontrollably. However, our genes contain information for much more than just proteins. In fact, only one percent of human DNA codes for proteins, the rest transcribes into what is called non-coding RNA whose functions vary widely. One type of non-coding RNA is called long non-coding RNA, or lncRNA. Unlike short or microRNA, lncRNA is much more difficult to study, leaving its function in cancer formation, progression, and in its response to treatment undefined.
To get a better handle on this class of RNA, a Jefferson team of researchers pooled functional data on over 800 cancer cell lines and ten different cancer types to identify lncRNAs that impact cancer growth and characterized their function. To do so, they had to create a first-of-its-kind integrative-, systems-, and network-biology approach that statistically mapped lncRNAs to critical pathways that cancer cells need to grow and survive. The research team of Ramkrishna Mitra, PhD, a research assistant professor, and Clare Adams, PhD, a research associate, led by Christine Eischen, PhD, the Herbert A. Rosenthal, MD ’56 professor of Cancer Research and leader of one of the four SKCC programs at Jefferson, published their findings in eLife.
They found that certain lncRNAs are regulated by the well-known tumor suppressor p53 and can slow tumor growth. What is most surprising is that these tumor-suppressing lncRNAs exist across different cancer types and are not tissue specific, hinting that these RNA molecules are a core component of cancer suppression. It also suggests that if medicines that increase and can maintain higher levels of these lncRNAs could be identified, these would be effective across multiple cancer types.
Dr. Eischen’s research findings have opened new avenues of possibility for tumor prognosis and tumor treatment in the future. Further, the methods developed by Dr. Ramkrishna Mitra allows lncRNAs to be studied more efficiently in both cancer and non-cancer applications by scientists around the world.
As the opioid epidemic has mounted over the last two decades, so too have cases of neonatal opioid withdrawal syndrome (NOWS). NOWS is a condition in which infants born to people who have used opioids during pregnancy experience withdrawal symptoms after birth. Treatment for NOWS can entail weeks in the hospital and may require morphine and other therapies to alleviate the potentially life-threatening withdrawal. A new study co-authored by Thomas Jefferson University Hospital’s Walter Kraft, MD, and Susan Adeniyi-Jones, MD, suggests that a common anti-nausea medication may help ease the symptoms of NOWS.
The study, published in the Journal of Perinatology, examines ondansetron for the treatment of NOWS. Ondansetron is an anti-nausea drug that works by blocking the 5HT-3 receptor, a subtype of serotonin receptor found in both the brain and GI tract. Previous research in mice revealed that the genes coding the 5HT-3 receptor were linked to opioid withdrawal symptoms, and that administration of ondansetron relieved those symptoms in both mice and adult humans.
To determine if the drug would also help infants with NOWS, the researchers administered ondansetron or a placebo to mothers with opioid use disorder during labor, and to their infants for five days after birth. The research team measured the efficacy of the ondansetron by the severity of the infants’ withdrawal symptoms and number of infants in each treatment group who required morphine.
The researchers found that infants treated with ondansetron experienced significantly less severe NOWS symptoms, supporting the drug as a potential future treatment. In addition, fewer of the ondansetron-treated infants required morphine compared to the placebo group; however, this difference was not statistically significant. Recent animal work showed that ondansetron does not easily enter the brain, so the researchers are planning future studies with higher doses or different routes of administration. “If we could get the levels high enough,” says Dr. Kraft, “I think we would come out with an endpoint that would demonstrate fewer babies would require opioid treatment.”
- By Marilyn Perkins
