The journey of a marathon sleeper

A marathon sleeper who got away left some clues for Emory and University of Florida scientists to Read more

A push for reproducibility in biomedical research

At Emory, several scientists are making greater efforts to push forward to improve scientific research and combat what is being called “the reproducibility crisis.” Guest post from Erica Read more

Exosomes as potential biomarkers of radiation exposure

Exosomes = potential biomarkers of radiation in the Read more

progesterone

No junk: long RNA mimics DNA, restrains hormone responses

It arises from what scientists previously described as “junk DNA” or “the dark matter of the genome,” but this gene is definitely not junk. The gene Gas5 acts as a brake on steroid hormone receptors, making it a key player in diseases such as hormone-sensitive prostate and breast cancer.

Unlike many genes scientists are familiar with, Gas5 does not encode a protein. It gets transcribed into RNA, like many other genes, but with Gas5 the RNA is what’s important, not the protein. The RNA accumulates in cells subjected to stress and soaks up steroid hormone receptors, preventing them from binding DNA and turning genes on and off.

Emory researchers have obtained a detailed picture of how the Gas5 RNA interacts with steroid hormone receptors. Their findings show how the Gas5 RNA takes the place of DNA, and give hints as to how it evolved.

The results were published Friday in Nature Communications.

Scientists used to think that much of the genome was “fly-over country”: not encoding any protein and not even accessed much by the cell’s gene-reading machinery. Recent studies have revealed that a large part of the genome is copied into lincRNAs (long intergenic noncoding RNAs), of which Gas5 is an example. Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Progesterone could become tool vs glioblastoma

The hormone progesterone could become part of therapy against the most aggressive form of brain cancer. High concentrations of progesterone kill glioblastoma cells and inhibit tumor growth when the tumors are implanted in mice, researchers have found.

The results were recently published in the Journal of Steroid Biochemistry and Molecular Biology.

Glioblastoma is the most common and the most aggressive form of brain cancer in adults, with average survival after diagnosis of around 15 months. Surgery, radiation and chemotherapy do prolong survival by several months, but targeted therapies, which have been effective with other forms of cancer, have not lengthened survival in patients fighting glioblastoma.

The lead author of the current paper is assistant professor of emergency medicine Fahim Atif, PhD. The findings with glioblastoma came out of Emory researchers’ work on progesterone as therapy for traumatic brain injury and more recently, stroke. Atif, Donald Stein and their colleagues have been studying progesterone for the treatment of traumatic brain injury for more than two decades, prompted by Stein’s initial observation that females recover from brain injury more readily than males. There is a similar tilt in glioblastoma as well: primary glioblastoma develops three times more frequently in males compared to females.

These results could pave the way for the use of progesterone against glioblastoma in a human clinical trial, perhaps in combination with standard-of-care therapeutic agents such as temozolomide. However, Stein says that more experiments are necessary with grafts of human tumor cells into animal brains first. His team identified a factor that may be important for clinical trial design: progesterone was not toxic to all glioblastoma cell lines, and its toxicity may depend on whether the tumor suppressor gene p53 is mutated.

Atif, Stein, and colleague Seema Yousuf found that low, physiological doses of progesterone stimulate the growth of glioblastoma tumor cells, but higher doses kill the tumor cells while remaining nontoxic for healthy cells. Similar effects have been seen with the progesterone antagonist RU486, but the authors cite evidence that progesterone is less toxic to healthy cells. Progesterone has also been found to inhibit growth of neuroblastoma cells (neuroblastoma is the most common cancer in infants), as well as breast, ovarian and colon cancers in cell culture and animal models.

 

Posted on by Quinn Eastman in Cancer, Neuro Leave a comment

Exception from informed consent: what patients say

Informed consent is a basic principle of clinical research. Doctors are required to make sure that patients understand what’s involved with experimental treatments, and patients should only participate if they provide consent.

However, an important area of clinical research takes place outside of this general rule, because some life-threatening conditions – seizures, traumatic brain injury and cardiac arrest, as examples — make it impossible for the patient to learn about a clinical trial and make a decision about whether to participate. The urgency of treatment can also mean that seeking proxy consent from a relative is impractical.

A recent editorial in USA Today highlights this area of research, called EFIC (exception from informed consent). The author, Katherine Chretien from George Washington University, cites research from Emory investigators Neal Dickert and Rebecca Pentz.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Next steps in progesterone for brain injury

At a recent Society for Neuroscience (SFN) meeting, Emory researchers described their efforts to learn about optimizing progesterone for treatment of traumatic brain injury.

Researcher Donald Stein, PhD, Asa G. Candler Professor of Emergency Medicine at Emory School of Medicine, has shown that progesterone can protect damaged brain tissue. Stein is director of the Department of Emergency Medicine’s Brain Research Laboratory.

Donald G. Stein, PhD

Donald G. Stein, PhD

One of the Emory SFN presentations covered efforts to find progesterone analogues that are more water soluble. This work comes from Stein and his colleagues in collaboration with the laboratory of Dennis Liotta, PhD, Emory professor of chemistry.

Currently, the lack of water solubility limits delivery of progesterone, in that the hormone must be prepared hours ahead and cannot be kept at room temperature. Small chemical modifications may allow similar compounds with the same effects as progesterone to be given to patients closer to the time of injury.

According to the results, two compounds similar to progesterone showed an equivalent ability to reduce brain swelling in an animal model of traumatic brain injury.

The second Emory report described evidence that adding vitamin D to progesterone enhances the hormone’s effectiveness when applied to neurons under stress in the laboratory. Like progesterone, vitamin D is a steroid hormone that is inexpensive, has good safety properties and acts on many different biochemical pathways.

David Wright, MD

David Wright, MD

The authors showed that a low amount of vitamin D boosted the ability of progesterone to protect neurons from excito-toxicity , a principal cause of brain injury and cell death.

A new study at Emory, slated to begin early 2010, will evaluate progesterone’s effectiveness for treating traumatic brain injury in a multisite phase III clinical trial called ProTECT III.

The study follows earlier findings that showed giving progesterone to trauma victims shortly after brain injury appears to be safe and may reduce the risk of death and long-term disability.

David Wright, MD, assistant professor of emergency medicine at Emory School of Medicine is the national study’s lead investigator.

Michael Frankel, MD, Emory professor of neurology, will serve as site principal investigator of the clinical trial at Grady Memorial Hospital.

Posted on by Quinn Eastman in Neuro Leave a comment