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!
New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia
New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences