The study, spearheaded by scientists at the University of North Carolina at Chapel Hill and involving collaborators at Albert Einstein College of Medicine of Yeshiva University and North Carolina Central University in Durham, is described in the November 5 issue of Science.
While the chemotherapy agent CPT-11 has proven useful in attacking colorectal tumors, it can also cause severe diarrhea - limiting the dosage that patients can tolerate and curbing the drug's potential effectiveness. The primary cause of the diarrhea is believed to be beta glucuronidase, an enzyme found in bacteria that live in the gastrointestinal tract.
After the liver has rendered CPT-11 inert, the drug enters the intestine where it's reactivated by the beta glucuronidase of the gut bacteria. The revived CPT-11 irritates the intestine and causes severe diarrhea in up to 30 percent of patients who receive it.
To overcome this crippling side effect, the UNC researchers decided to look for compounds that would block the action of beta glucuronidase without eliminating the gut bacteria, which are important for human health.
"We need to retain our intestinal bacteria – they help us digest food, make critical vitamins and protect us from infection," said Matthew R. Redinbo, Ph.D., who led the UNC research team, and is professor and chair of the chemistry department in the UNC College of Arts and Sciences and a member of the UNC Lineberger Comprehensive Cancer Center. "This targeted approach stops the one bacterial protein thought to cause the drug's devastating side effect, but without damaging the beneficial microbes or the intestines."
Study co-author, Sridhar Mani, M.D., professor of medicine and of genetics at Einstein, said the severe diarrhea caused by CPT-11 can sharply limit the dosage that cancer patients can receive. "Our tests showed conclusively that the inhibitor identified by our UNC colleagues prevented diarrhea in mice that were also receiving CPT-11. We're hopeful that clinical trials will show that administering this inhibitor when patients start taking CPT-11 allows for improvement in the drug's anti-tumor effect in patients with cancer."
The research was funded by the National Institutes of Health, the Golden Leaf Foundation and the State of North Carolina.
Other study co-authors were graduate students Bret D. Wallace and Jillian Orans, and postdoctoral fellow Kimberly T. Lane, Ph.D., all from the UNC chemistry department; Ja Seol Koo, M.D., and Christian Jobin, Ph.D., from the medicine department in the UNC School of Medicine; Hongwei Wang, Ph.D. and Madhukumar Venkatesh, Ph.D., from the departments of medicine, oncology and genetics at Albert Einstein College of Medicine; and John E. Scott, Ph.D., and Li-An Yeh, Ph.D., with the Biomanufacturing Research Institute and Technology Enterprise program at N.C. Central University.UNC News Services contact:
Patric Lane | EurekAlert!
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.
Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
23.01.2018 | Life Sciences
23.01.2018 | Earth Sciences
23.01.2018 | Physics and Astronomy