BreakThrough Digest Medical News |
| Common antifungal drug decreases tumor growth and shows promise as cancer therapy Posted: 20 Aug 2012 09:00 PM PDT An inexpensive antifungal drug, thiabendazole, slows tumor growth and shows promise as a chemotherapy for cancer. Scientists in the College of Natural Sciences at The University of Texas at Austin made this discovery by exploiting the evolutionary relatedness of yeast, frogs, mice and humans.
Thiabendazole is an FDA-approved, generic drug taken orally that has been in clinical use for 40 years as an antifungal. It is not currently used for cancer therapy. Hye Ji Cha, Edward Marcotte, John Wallingford and colleagues found that the drug destroys newly established blood vessels, making it a “vascular disrupting agent.” Their research was published in the journal PLOS Biology. Inhibiting blood vessel, or vascular, growth can be an important chemotherapeutic tool because it starves tumors. Tumors induce new blood vessel formation to feed their out-of-control growth. In trials using mice, the researchers found that thiabendazole decreased blood vessel growth in fibrosarcoma tumors by more than a half. Fibrosarcomas are cancers of the connective tissue, and they are generally heavily vascularized with blood vessels. The drug also slowed tumor growth. “This is very exciting to us, because in a way we stumbled into discovering the first human-approved vascular disrupting agent,” said Marcotte, professor of chemistry. “Our research suggests that thiabendazole could probably be used clinically in combination with other chemotherapies.” The scientists’ discovery is a culmination of research that crosses disciplines and organisms. In a previous study, Marcotte and his colleagues found genes in single-celled yeast that are shared with vertebrates by virtue of their shared evolutionary history. In yeasts, which have no blood vessels, the genes are responsible for responding to various stresses to the cells. In vertebrates, the genes have been repurposed to regulate vein and artery growth, or angiogenesis. “We reasoned that by analyzing this particular set of genes, we might be able to identify drugs that target the yeast pathway that also act as angiogenesis inhibitors suitable for chemotherapy,” said Marcotte. Turns out they were right. Cha, a graduate student in cell and molecular biology at the university, searched for a molecule that would inhibit the action of those yeast genes. She found that thiabendazole did the trick. She then tested the drug in developing frog embryos. These are fast growing vertebrates in which scientists can watch blood vessel growth in living animals. Cha found that frog embryos grown in water with the drug either didn’t grow blood vessels or grew blood vessels that were then dissolved away by the drug. Interestingly, when the drug was removed, the embryos’ blood vessels grew back. Cha then tested the drug on human blood vessel cells growing in Petri dishes, finding that the drug also inhibited their growth. Finally, she tested the drug on fibrosarcoma tumors in mice and found that it reduced blood vessel growth in the tumors as well as slowed the tumors’ growth. “We didn’t set out to find a vascular disrupting agent, but that’s where we ended up,” said Wallingford, associate professor of developmental biology and Cha’s graduate advisor with Marcotte. “This is an exciting example of the power of curiosity-driven research and the insights that can come from blending disciplines in biology.” The scientists’ goal is now to move the drug into clinical trials with humans. They are talking with clinical oncologists about next steps. “We hope the clinical trials will be easier because it is already approved by the FDA for human use,” said Marcotte. ### Funding for this research came from the Cancer Prevention Research Institute of Texas (CPRIT), the Welch Foundation, the National Institutes of Health (grant numbers GM067779 and GM088624) and the Howard Hughes Medical Institute (HHMI). Marcotte is the Mr. and Mrs. Corbin J. Robertson, Sr. Regents Chair in Molecular Biology. Wallingford is an HHMI Early Career Scientist. Additional contacts: Edward Marcotte, professor, 512-471-5435, marcotte@icmb.utexas.edu; John Wallingford, professor, 512-232-2784; wallingford@mail.utexas.edu Contact: Lee Clippard |
| Groundbreaking clinical trial looks at fecal transplant as treatment for C. difficile Posted: 20 Aug 2012 09:00 PM PDT For patients with Clostridium difficile (C. difficile), a persistent and potentially deadly bacterial illness, severe diarrhea, abdominal pain, nausea and vomiting are an everyday event. This particularly virulent infection is prone to recurrence, even after multiple courses of expensive antibiotics, and treatment options are limited for patients who continually relapse or develop antibiotic resistance.
Now, a new National Institutes of Health research grant awarded to Colleen Kelly, M.D., a gastroenterologist with the Center for Women’s Gastrointestinal Medicine at the Women’s Medicine Collaborative, and co-investigator Lawrence Brandt, M.D., from the Albert Einstein School of Medicine in New York, will test whether an unconventional yet promising treatment known as fecal bacteriotherapy, or fecal transplantation, is an effective therapy for patients with relapsing C. difficile. While it sounds unpleasant, previous research suggests fecal transplantation, which involves transplanting healthy donor stool into the patient’s colon during a colonoscopy, is extremely successful; according to published case studies, the procedure has “cured” relapsing C. difficile in 89 percent of patients without any complications. However, few physicians know about the procedure, which has been around for more than 50 years, and to date there have been no published prospective clinical trials of fecal transplant for C. difficile. Kelly’s research will be the first randomized controlled clinical trial of this procedure as a treatment for relapsing C. difficile. “Our goal is to clearly demonstrate to both the medical community and health insurers that fecal transplant is an viable, safe, inexpensive, and ultimately curative treatment for patients with relapsing C. difficile,” said Kelly. “We hope this research is the first step toward developing standard treatment protocols for this procedure and making it more widely available to the many patients who are suffering from recurring C. difficle.” C. difficile affects tens of thousands of Americans each year, particularly patients in hospitals or long-term care facilities, and typically occurs after a dose of antibiotic medications. It has been increasing in both incidence and severity over the last decade, including otherwise healthy people who aren’t hospitalized or taking antibiotics. It causes 14,000 deaths annually, according to the Centers for Disease Control and Prevention. C. difficile disrupts the balance of the normal, healthy, protective bacterial flora found in the colon. When that happens ? often following a dose of antibiotics ? invasive bacteria like C. difficile can grow, proliferate and produce toxins that make patients sick. Approximately 20 percent of patients have recurring C. difficile that does not respond to antibiotics. Patients who experience one recurrence have a 40 percent risk of further relapse, while those with two or more episodes face a 60 percent relapse risk. While the first relapse is generally treated with a second course of antibiotics, current guidelines recommend a tapering course of an expensive antibiotic known as oral vancomycin following a second recurrence. During a fecal transplant, healthy donor stool is mixed with saline and infused into the colon during a standard outpatient colonoscopy procedure. The patient identifies the donor ? usually a family member or close friend ? ahead of time, and the donor undergoes a rigorous screening process. A stool sample is obtained the morning of the procedure. Kelly, who is also a clinical assistant professor of medicine at The Warren Alpert Medical School of Brown University, says fecal transplant works because the donor stool contains the healthy bacteria needed to restore and repopulate the patient’s colon with what she calls an “army of good bacteria” to keep C. difficle from overgrowing and causing disease. Kelly and Brandt hope to enroll 48 patients in this randomized study, which will determine if fecal transplantation, using stool from a healthy volunteer donor, provides a cure for relapsing C. difficile infection. Collaborating investigators at the University of Minnesota will analyze the complex bacterial communities in stool collected from patients both before and after transplant, as well as their donors. “Given the increasing incidence and severity of C. difficile infection, the problem of recurrent disease in a significant number of patients, and the economic burden and drug-resistant infections associated with long term use of oral antibiotics, we need this clinical trial to determine whether fecal transplant is an effective treatment for relapsing infection,” said Kelly. ### About the Women’s Medicine Collaborative
The Women’s Medicine Collaborative (www.womensmedicine.org) is Rhode Island’s largest multi-specialty center dedicated to caring for women at all stages of life. The Collaborative offers coordinated, patient-centered and personalized care all under one roof, including obstetric medicine, women’s primary care, women’s behavioral medicine, specialty services for non-pregnant and pregnant women, and the Center for Women’s Gastrointestinal Medicine. All care is provided by women, and physicians and nurse practitioners are all board certified, with many serving as faculty at The Warren Alpert Medical School of Brown University. The Women’s Medicine Collaborative is a Lifespan partner. Follow us on Facebook (www.facebook.com/womensmedicine) and on Twitter (@WomensMedicine). This research is supported by the National Institutes of Health under Award Number R21 DK093839-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Contact: Jessica Collins Grimes |
| You are subscribed to email updates from BreakThrough Digest Medical News To stop receiving these emails, you may unsubscribe now. | Email delivery powered by Google |
| Google Inc., 20 West Kinzie, Chicago IL USA 60610 | |
